Artificial insemination

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https://en.wikipedia.org/wiki/Artificial_insemination

Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment for humans, and is a common practice in animal breeding, including dairy cattle (see Frozen bovine semen) and pigs.

Artificial insemination may employ assisted reproductive technology, sperm donation and animal husbandry techniques. Artificial insemination techniques available include intracervical insemination (ICI) and intrauterine insemination (IUI).

Humans

History

The first recorded case of artificial insemination was John Hunter in 1790, who helped impregnate a linen draper's wife. The first reported case of artificial insemination by donor occurred in 1884: William H. Pancoast, a professor in Philadelphia, took sperm from his "best looking" student to inseminate an anesthetized woman without her knowledge. The case was reported 25 years later in a medical journal. The sperm bank was developed in Iowa starting in the 1950s in research conducted by University of Iowa medical school researchers Jerome K. Sherman and Raymond Bunge.

In the United Kingdom, the British obstetrician Mary Barton founded one of the first fertility clinics to offer donor insemination in the 1930s, with her husband Bertold Wiesner fathering hundreds of offspring.

In the 1980s, direct intraperitoneal insemination (DIPI) was occasionally used, where doctors injected sperm into the lower abdomen through a surgical hole or incision, with the intention of letting them find the oocyte at the ovary or after entering the genital tract through the ostium of the fallopian tube.

General

The sperm used in artificial insemination may be provided by either the woman's husband or partner (partner sperm) or by a known or anonymous sperm donor (see sperm donation (donor sperm)). The beneficiaries of artificial insemination are women who desire to give birth to their own child who may be single, women who are in a lesbian relationship or women who are in a heterosexual relationship but with a male partner who is infertile or who has a physical impairment which prevents full intercourse from taking place. Artificial insemination techniques were originally used mainly to assist heterosexual couples to conceive where they were having difficulties. With the advancement of techniques in this field, notably ICSI, the use of artificial insemination for such couples has largely been rendered unnecessary. However, there are still reasons why a couple would seek to use artificial insemination using the male partner's sperm. In the case of such couples, before artificial insemination is turned to as the solution, doctors will require an examination of both the male and female involved in order to remove any and all physical hindrances that are preventing them from naturally achieving a pregnancy including any factors which prevent the couple from having satisfactory sexual intercourse. The couple is also given a fertility test to determine the motility, number, and viability of the male's sperm and the success of the female's ovulation. From these tests, the doctor may or may not recommend a form of artificial insemination. The results of investigations may, for example, show that the woman's immune system may be rejecting her partner's sperm as invading molecules. Women who have issues with the cervix – such as cervical scarring, cervical blockage from endometriosis, or thick cervical mucus – may also benefit from artificial insemination, since the sperm must pass through the cervix to result in fertilization.

Nowadays artificial insemination in humans is mainly used as a substitute for sexual intercourse for women without a male partner who wish to have their own children and who do so where sperm from a sperm donor is used. Donor sperm may be used in other ways, such as IVF and ICSI and a woman having a baby by a sperm donor will usually also have these methods available to her as alternatives to artificial insemination. Intracervical insemination is the easiest and most common insemination technique and can be used in the home for self-insemination without medical practitioner assistance. Compared with natural insemination (i.e., insemination by sexual intercourse), artificial insemination can be more expensive and more invasive, and may require professional assistance.

Some countries have laws which restrict and regulate who can donate sperm and who is able to receive artificial insemination, and the consequences of such insemination. Some women who live in a jurisdiction which does not permit artificial insemination in the circumstance in which she finds herself may travel to another jurisdiction which permits it.

If the procedure is successful, the woman will conceive and carry a baby to term in the normal manner. A pregnancy resulting from artificial insemination is no different from a pregnancy achieved by sexual intercourse. In all cases of artificial insemination, the recipient woman will be the biological mother of any child produced, and the male whose sperm is used will be the biological father.

There are multiple methods used to obtain the semen necessary for artificial insemination. Some methods require only men, while others require a combination of a male and female. Those that require only men to obtain semen are masturbation or the aspiration of sperm by means of a puncture of the testicle and epydidymus. Methods of collecting semen that involve a combination of a male and female include interrupted intercourse, intercourse with a 'collection condom', or the post-coital aspiration of the semen from the vagina.

Preparations

Timing is critical, as the window and opportunity for fertilization is little more than twelve hours from the release of the ovum. To increase the chance of success, the woman's menstrual cycle is closely observed, often using ovulation kits, ultrasounds or blood tests, such as basal body temperature tests over, noting the color and texture of the vaginal mucus, and the softness of the nose of her cervix. To improve the success rate of artificial insemination, drugs to create a stimulated cycle may be used, but the use of such drugs also results in an increased chance of a multiple birth.

Sperm can be provided fresh or washed. Washed sperm is required in certain situations. Pre- and post-concentration of motile sperm is counted. Sperm from a sperm bank will be frozen and quarantined for a period, and the donor will be tested before and after production of the sample to ensure that he does not carry a transmissible disease. Sperm from a sperm bank will also be suspended in a semen extender which assists with freezing, storing and shipping.

If sperm is provided by a private donor, either directly or through a sperm agency, it is usually supplied fresh, not frozen, and it will not be quarantined. Donor sperm provided in this way may be given directly to the recipient woman or her partner, or it may be transported in specially insulated containers. Some donors have their own freezing apparatus to freeze and store their sperm.

Techniques

The human female reproductive system. The cervix is part of the uterus. The cervical canal connects the interiors of the uterus and vagina.

Semen used is either fresh, raw, or frozen. Where donor sperm is supplied by a sperm bank, it will always be quarantined and frozen, and will need to be thawed before use. The sperm is ideally donated after two or three days of abstinence, without lubrication as the lubricant can inhibit the sperm motility. When an ovum is released, semen is introduced into the woman's vagina, uterus or cervix, depending on the method being used.

Sperm is occasionally inserted twice within a 'treatment cycle'.

Intracervical

Intracervical insemination (ICI) is the method of artificial insemination which most closely simulates the natural ejaculation of semen by the penis into the vagina during sexual intercourse. It is painless and is the simplest, easiest and most common method of artificial insemination involving the introduction of unwashed or raw semen into the vagina at the entrance to the cervix, usually by means of a needleless syringe.

ICI is commonly used in the home, by self-insemination and practitioner insemination. Sperm used in ICI inseminations does not have to be 'washed' to remove seminal fluid so that raw semen from a private donor may be used. Semen supplied by a sperm bank prepared for ICI or IUI use is suitable for ICI. ICI is a popular method of insemination amongst single and lesbian women purchasing donor sperm on-line.

Although ICI is the simplest method of artificial insemination, a meta-analysis has shown no difference in live birth rates compared with IUI. It may also be performed privately by the woman, or, if she has a partner, in the presence of her partner, or by her partner. ICI was previously used in many fertility centers as a method of insemination, although its popularity in this context has waned as other, more reliable methods of insemination have become available.

During ICI, air is expelled from a needleless syringe which is then filled with semen which has been allowed to liquify. A specially-designed syringe, wider and with a more rounded end, may be used for this purpose. Any further enclosed air is removed by gently pressing the plunger forward. The woman lies on her back and the syringe is inserted into the vagina. Care is optimal when inserting the syringe, so that the tip is as close to the entrance to the cervix as possible. A vaginal speculum may be used for this purpose and a catheter may be attached to the tip of the syringe to ensure delivery of the semen as close to the entrance to the cervix as possible. The plunger is then slowly pushed forward and the semen in the syringe is gently emptied deep into the vagina. It is important that the syringe is emptied slowly for safety and for the best results, bearing in mind that the purpose of the procedure is the replicate as closely as possible a natural deposit of the semen in the vagina. The syringe (and catheter if used) may be left in place for several minutes before removal. The woman can bring herself to orgasm so that the cervix 'dips down' into the pool of semen, again replicating closely vaginal intercourse, and this may improve the success rate.

Following insemination, fertile sperm will swim through the cervix into the uterus and from there to the fallopian tubes in a natural way as if the sperm had been deposited in the vagina through intercourse. The woman is therefore advised to lie still for about half-an-hour to assist conception.

One insemination during a cycle is usually sufficient. Additional inseminations during the same cycle may not improve the chances of a pregnancy.

Ordinary sexual lubricants should not be used in the process, but special fertility or 'sperm-friendly' lubricants can be used for increased ease and comfort.

When performed at home without the presence of a professional, aiming the sperm in the vagina at the neck of the cervix may be more difficult to achieve and the effect may be to 'flood' the vagina with semen, rather than to target it specifically at the entrance to the cervix. This procedure is sometimes referred to as 'intravaginal insemination' (IVI). Sperm supplied by a sperm bank will be frozen and must be allowed to thaw before insemination. The sealed end of the straw itself must be cut off and the open end of the straw is usually fixed straight on to the tip of the syringe, allowing the contents to be drawn into the syringe. Sperm from more than one straw can generally be used in the same syringe. Where fresh semen is used, this must be allowed to liquefy before inserting it into the syringe, or alternatively, the syringe may be back-loaded.

A conception cap, which is a form of conception device, may be inserted into the vagina following insemination and may be left in place for several hours. Using this method, a woman may go about her usual activities while the cervical cap holds the semen in the vagina close to the entrance to the cervix. Advocates of this method claim that it increases the chances of conception. One advantage with the conception device is that fresh, non-liquefied semen may be used. The man may ejaculate straight into the cap so that his fresh semen can be inserted immediately into the vagina without waiting for it to liquefy, although a collection cup may also be used. Other methods may be used to insert semen into the vagina notably involving different uses of a conception cap. These include a specially designed conception cap with a tube attached which may be inserted empty into the vagina after which liquefied semen is poured into the tube. These methods are designed to ensure that semen is inseminated as close as possible to the cervix and that it is kept in place there to increase the chances of conception.

Intrauterine

Intrauterine insemination (IUI) involves injection of washed sperm directly into the uterus with a catheter. Insemination in this way means that the sperm do not have to swim through the cervix which is coated with a mucus layer. This layer of mucus can slow down the passage of sperm and can result in many sperm perishing before they can enter the uterus. Donor sperm is sometimes tested for mucus penetration if it is to be used for ICI inseminations but partner sperm may or may not be able to pass through the cervix. In these cases, the use of IUI can provide a more efficient delivery of the sperm. In general terms, IUI is usually regarded as more efficient than ICI or IVI. It is therefore the method of choice for single and lesbian women wishing to conceive using donor sperm since this group of recipients usually require artificial insemination because they do not have a male partner, not because they have medical problems. Owing to the high number of these recipients using donor sperm services, IUI is therefore the most popular method of insemination today at a fertility clinic. The term 'artificial insemination' has, in many cases, come to mean IUI insemination.

It is important that washed sperm is used because unwashed sperm may elicit uterine cramping, expelling the semen and causing pain, due to content of prostaglandins. (Prostaglandins are also the compounds responsible for causing the myometrium to contract and expel the menses from the uterus, during menstruation.) Resting on the table for fifteen minutes after an IUI is optimal for the woman to increase the pregnancy rate.

Using this technique, as with ICI, fertilisation takes place naturally in the external part of the fallopian tubes in the same way that occurs following intercourse.

For heterosexual couples, the indications to perform an intrauterine insemination are usually a moderate male factor, the incapability to ejaculate in vagina and an idiopathic infertility. A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates. For the man, a TMS of more than 5 million per ml is optimal. In practice, donor sperm will satisfy these criteria and since IUI is a more efficient method of artificial insemination than ICI and, because of its generally higher success rate, IUI is usually the insemination procedure of choice for single women and lesbians using donor semen in a fertility centre. Lesbians and single women are less likely to have fertility issues of their own and enabling donor sperm to be inserted directly into the womb will often produce a better chance of conceiving.

Lesbian couples may either select a friend or family member as their sperm donor or choose an anonymous donor. After a donor sperm is selected, a couple can proceed with donor sperm IUI. IUI is the least expensive option for same-sex couples and can be done without the use of medication. According to a study from 2021, lesbian women undergoing IUI had a clinical pregnancy rate of 13.2% per cycle and 42.2% success rate given the average number of cycles at 3.6.

Unlike ICI, intrauterine insemination normally requires a medical practitioner to perform the procedure. One of the requirements is to have at least one permeable tube, proved by hysterosalpingography. The infertility duration is also important. A female under 30 years of age has optimal chances with IUI; A promising cycle is one that offers two follicles measuring more than 16 mm, and estrogen of more than 500 pg/mL on the day of hCG administration. However, GnRH agonist administration at the time of implantation does not improve pregnancy outcome in intrauterine insemination cycles according to a randomized controlled trial.^[23] One of the prominent private clinic in Europe has published a data A multiple logistic regression model showed that sperm origin, maternal age, follicle count at hCG administration day, follicle rupture, and the number of uterine contractions observed after the second insemination procedure were associated with the live-birth rate. The steps to follow in order to perform an intrauterine insemination are:

• Mild Controlled Ovarian Stimulation (COS): there is no control of how many oocytes are at the same time when stimulating ovulation. For that reason, it is necessary to check the amount being ovulated via ultrasound (checking the amount of follicles developing at the same time) and administering the desired amount of hormones.
• Ovulation Induction: using substances known as ovulation inductors.
• Semen capacitation: wash and centrifugation, swim-up, or gradient. The insemination should not be performed later than an hour after capacitation. 'Washed sperm' may be purchased directly from a sperm bank if donor semen is used, or 'unwashed semen' may be thawed and capacitated before performing IUI insemination, provided that the capacitation leaves a minimum of, usually, five million motile sperm.
• Luteal Phase support: a lack of progesterone in the endometrium could end a pregnancy. To avoid that 200 mg/day of micronized progesterone are administered via vagina. If there is pregnancy, this hormone is kept administering until the tenth week of pregnancy.

IUI can be used in conjunction with controlled ovarian hyperstimulation (COH). Clomiphene Citrate is the first line, Letrozole is second line, in order to stimulate ovaries before moving on to IVF. Still, advanced maternal age causes decreased success rates; women aged 38–39 years appear to have reasonable success during the first two cycles of ovarian hyperstimulation and IUI. However, for women aged over 40 years, there appears to be no benefit after a single cycle of COH/IUI. Medical experts therefore recommend considering in vitro fertilization after one failed COH/IUI cycle for women aged over 40 years.

A double intrauterine insemination theoretically increases pregnancy rates by decreasing the risk of missing the fertile window during ovulation. However, a randomized trial of insemination after ovarian hyperstimulation found no difference in live birth rate between single and double intrauterine insemination. A Cochrane found uncertain evidence about the effect of IUI compared with timed intercourse or expectant management on live birth rates but IUI with controlled ovarian hyperstimulation is probably better than expectant management.

Due to the lack of reliable evidence from controlled clinical trials, it is not certain which semen preparation techniques are more effective (wash and centrifugation; swim-up; or gradient) in terms of pregnancy and live birth rates.

Intrauterine tuboperitoneal

Intrauterine tuboperitoneal insemination (IUTPI) involves injection of washed sperm into both the uterus and fallopian tubes. The cervix is then clamped to prevent leakage to the vagina, best achieved with a specially designed double nut bivalve (DNB) speculum. The sperm is mixed to create a volume of 10 ml, sufficient to fill the uterine cavity, pass through the interstitial part of the tubes and the ampulla, finally reaching the peritoneal cavity and the Pouch of Douglas where it would be mixed with the peritoneal and follicular fluid. IUTPI can be useful in unexplained infertility, mild or moderate male infertility, and mild or moderate endometriosis. In non-tubal sub fertility, fallopian tube sperm perfusion may be the preferred technique over intrauterine insemination.

Intratubal

Intratubal insemination (ITI) involves injection of washed sperm into the fallopian tube, although this procedure is no longer generally regarded as having any beneficial effect compared with IUI. ITI however, should not be confused with gamete intrafallopian transfer, where both eggs and sperm are mixed outside the woman's body and then immediately inserted into the fallopian tube where fertilization takes place.

Pregnancy rate

Approximate pregnancy rate as a function of total sperm count (may be twice as large as total motile sperm count). Values are for intrauterine insemination. (Old data, rates are likely higher these days)

Main article: Pregnancy rate

The rates of successful pregnancy for artificial insemination are 10-15% per menstrual cycle using ICI, and 15–20% per cycle for IUI. In IUI, about 60 to 70% have achieved pregnancy after 6 cycles.

However, these pregnancy rates may be very misleading, since many factors have to be included to give a meaningful answer, e.g. definition of success and calculation of the total population. These rates can be influenced by age, overall reproductive health, and if the patient had an orgasm during the insemination. The literature is conflicting on immobilization after insemination has increasing the chances of pregnancy  Previous data suggests that it is statistically significant for the patient to remain immobile for 15 minutes after insemination, while another review article claims that it is not. A point of consideration, is that it does cost the patient or healthcare system to remain immobile for 15 minutes if it does increase the chances. For couples with unexplained infertility, unstimulated IUI is no more effective than natural means of conception.

The pregnancy rate also depends on the total sperm count, or, more specifically, the total motile sperm count (TMSC), used in a cycle. The success rate increases with increasing TMSC, but only up to a certain count, when other factors become limiting to success. The summed pregnancy rate of two cycles using a TMSC of 5 million (may be a TSC of ~10 million on graph) in each cycle is substantially higher than one single cycle using a TMSC of 10 million. However, although more cost-efficient, using a lower TMSC also increases the average time taken to achieve pregnancy. Women whose age is becoming a major factor in fertility may not want to spend that extra time.

Samples per child

The number of samples (ejaculates) required to give rise to a child varies substantially from person to person, as well as from clinic to clinic. However, the following equations generalize the main factors involved:

For intracervical insemination:

${\displaystyle N=\frac{V_s\times c\times r_s}{n_r}}$

• N is how many children a single sample can give rise to.
• V_s is the volume of a sample (ejaculate), usually between 1.0 mL and 6.5 mL
• c is the concentration of motile sperm in a sample after freezing and thawing, approximately 5–20 million per ml but varies substantially
• r_s is the pregnancy rate per cycle, between 10% and 35% 
• n_r is the total motile sperm count recommended for vaginal insemination (VI) or intra-cervical insemination (ICI), approximately 20 million pr. ml.

The pregnancy rate increases with increasing number of motile sperm used, but only up to a certain degree, when other factors become limiting instead.

Derivation of the equation (click at right to view)

Approximate live birth rate (r_s) among infertile couples as a function of total motile sperm count (n_r). Values are for intrauterine insemination.

With these numbers, one sample would on average help giving rise to 0.1–0.6 children, that is, it actually takes on average 2–5 samples to make a child.

For intrauterine insemination, a centrifugation fraction (f_c) may be added to the equation:

f_c is the fraction of the volume that remains after centrifugation of the sample, which may be about half (0.5) to a third (0.33).

${\displaystyle N=\frac{V_s\times f_c\times c\times r_s}{n_r}}$

On the other hand, only 5 million motile sperm may be needed per cycle with IUI (n_r=5 million)

Thus, only 1–3 samples may be needed for a child if used for IUI.

Social implications

One of the key issues arising from the rise of dependency on assisted reproductive technology (ARTs) is the pressure placed on couples to conceive, "where children are highly desired, parenthood is culturally mandatory, and childlessness socially unacceptable".

The medicalization of infertility creates a framework in which individuals are encouraged to think of infertility quite negatively. In many cultures donor insemination is religiously and culturally prohibited, often meaning that less accessible "high tech" and expensive ARTs, like IVF, are the only solution.

An over-reliance on reproductive technologies in dealing with infertility prevents many – especially, for example, in the "infertility belt" of central and southern Africa – from dealing with many of the key causes of infertility treatable by artificial insemination techniques; namely preventable infections, dietary and lifestyle influences.

If good records are not kept, the offspring when grown up risk accidental incest.

Legal restrictions

Some countries restrict artificial insemination in a variety of ways. For example, some countries do not permit AI for single women, and other countries do not permit the use of donor sperm.

As of May 2013, the following European countries permit medically assisted AI for single women:

• Belarus
• Belgium
• Britain
• Bulgaria
• Denmark
• Estonia
• Finland
• Germany
• Greece
• Hungary
• Iceland
• Ireland
• Latvia
• Moldova
• Montenegro
• Netherlands
• North Macedonia
• Romania
• Russia
• Spain
• Ukraine
• Armenia
• Cyprus

Law in the United States

History of Law Around Artificial Insemination

Artificial insemination used to be seen as adultery and was illegal until the 1960s when states started recognizing the child born from artificial insemination as legitimate. Once the children began to be recognized as legitimate, legal questions around who the parents of the child are, how to handle surrogacy, paternity rights, and eventually artificial insemination and LGBT+ parents began to arise. Prior to the use of artificial insemination, the legal parents of a child were the two people who conceived the child or the person who birthed the child and their legal spouse, but artificial insemination complicates the legal process of becoming a parent as well as who is the parent of the child. Deciding who the parents of the child are is the largest legal predicament around artificial insemination. However, questions around surrogacy and donor’s rights also appear as a side question to determining the parent(s). Some major cases that deal with artificial insemination and parental rights are, K.M v E.G, Johnson v Calvert, Matter of Baby M, and In Re K.M.H.

Legal Parental Relations and Artificial Insemination

When children are conceived the traditional way, there is little discrepancy around who the legal parents of the child are. However, because children conceived using artificial insemination may not be genetically related to one or more of their parents, who the legal parents of the child are can come into question. Prior to the  passage of the Uniform Parentage Act  in 1973, children conceived via artificial insemination were deemed as “illegitimate” children. The Uniform Parentage Act then recognized the children born from artificial insemination as legal and laid precedent for how the legal parents of the child were decided. However, this act only applied to the children of those married couples. It established that the person who birthed the child was the mother and the father would be the husband of the woman. In 2002, the Uniform Parentage Act, which is adopted individually on a state by state basis, was revised to address non married couples and states that an unmarried couple has the same rights to the child that a married couple would. This extended who has the right to be a parent to a man who would supposedly fill in the social role as a “father.” There were now numerous ways to establish parental rights for both the mother and the father depending on if the child was born using a sperm donor or a surrogate. Currently, a revised version of the Uniform Parentage Act is starting to be passed in a few states that expands how parental relations can be determined. This bill includes expanding “father” to mean any person who would fill the role of a father, regardless of their gender and “mother” is expanded to anyone who gives birth to the child regardless of gender. In addition, this act would also change any language of “husband” or “wife” to “spouse.”

Paternity rights

There is no federal law that applies to all fifty states when it comes to artificial insemination and paternity rights, but the Uniform Parentage Act is a model which many states have adopted. Under the 1973 UPA, married heterosexual couples making use of artificial insemination through a licensed physician could list the husband as the natural father of the child, rather than the sperm donor. Since then a revised version of the Act has been introduced, though to less widespread adoption.

Generally paternity is not an issue when artificial insemination is between a married woman and an anonymous donor. Most states provide that anonymous donors' paternity claims are not recognized, and most sperm donation centers make use of contracts that require donors to sign away their paternity rights before they can participate. When the mother knows the donor, however, or engages in artificial insemination while unmarried, complications may arise. In cases of private sperm donation, paternity rights and responsibilities are often conferred onto sperm donors when: the donor and recipient did not comply with state laws regarding artificial insemination, the sperm donor and recipient know one another, or the donor had the intent of being a father to the child. When one or a number of these things is true, courts have at times found written agreements relinquishing parental rights to be unenforceable.

Opposition and criticism

Main article: Religious response to assisted reproductive technology

Some theologically-buttressed arguments reject the moral validity of this practice, such as Pope John XXIII. However, according to a document of the USCCB, the intrauterine insemination (IUI) of “licitly obtained” (normal intercourse with a silastic sheath i.e. a perforated condom) but technologically prepared semen sample (washed, etc.) has been neither approved nor disapproved by Church authority and its moral validity remains under discussion.

Other animals

A man performing artificial insemination of a cow.

A breeding mount with built-in artificial vagina used in semen collection from horses for use in artificial insemination

Artificial insemination is used for pets, livestock, endangered species, and animals in zoos or marine parks difficult to transport.

Reasons and techniques

See also: Captive breeding

It may be used for many reasons, including to allow a male to inseminate a much larger number of females, to allow the use of genetic material from males separated by distance or time, to overcome physical breeding difficulties, to control the paternity of offspring, to synchronize births, to avoid injury incurred during natural mating, and to avoid the need to keep a male at all (such as for small numbers of females or in species whose fertile males may be difficult to manage).

Artificial insemination is much more common than natural mating, as it allows several female animals to be impregnated from a single male. For instance, up to 30-40 female pigs can be impregnated from a single boar. Workers collect the semen by masturbating the boars, then insert it into the sows via a raised catheter known as a pork stork. Boars are still physically used to excite the females prior to insemination, but are prevented from actually mating.

Semen is collected, extended, then cooled or frozen. It can be used on-site or shipped to the female's location. If frozen, the small plastic tube holding the semen is referred to as a straw. To allow the sperm to remain viable during the time before and after it is frozen, the semen is mixed with a solution containing glycerol or other cryoprotectants. An extender is a solution that allows the semen from a donor to impregnate more females by making insemination possible with fewer sperm. Antibiotics, such as streptomycin, are sometimes added to the sperm to control some bacterial venereal diseases. Before the actual insemination, estrus may be induced through the use of progestogen and another hormone (usually PMSG or Prostaglandin F2α).

History

Artificial insemination tools brought from the USSR by Luis Thomasset in 1935 to work at Cambridge Laboratories and South America.

The first viviparous animal to be artificially fertilized was a dog. The experiment was conducted with success by the Italian Lazzaro Spallanzani in 1780. Another pioneer was the Russian Ilya Ivanov in 1899. In 1935, diluted semen from Suffolk sheep was flown from Cambridge in Britain to Kraków, Poland, as part of an international research project. The participants included Prawochenki (Poland), Milovanoff (USSR), Hammond and Walton (UK), and Thomasset (Uruguay).

Modern artificial insemination was pioneered by John O. Almquist of Pennsylvania State University. He improved breeding efficiency by the use of antibiotics (first proven with penicillin in 1946) to control bacterial growth, decreasing embryonic mortality, and increase fertility. This, and various new techniques for processing, freezing, and thawing of frozen semen significantly enhanced the practical utilization of artificial insemination in the livestock industry and earned him the 1981 Wolf Foundation Prize in Agriculture. Many techniques developed by him have since been applied to other species, including humans.

Species

Artificial insemination is used in many non-human animals, including sheep, horses, cattle, pigs, dogs, pedigree animals generally, zoo animals, turkeys and creatures as tiny as honeybees and as massive as orcas (killer whales).

Artificial insemination of farm animals is common in the developed world, especially for breeding dairy cattle (75% of all inseminations). Swine are also bred using this method (up to 85% of all inseminations). It is an economical means for a livestock breeder to improve their herds utilizing males having desirable traits.

Although common with cattle and swine, artificial insemination is not as widely practiced in the breeding of horses. A small number of equine associations in North America accept only horses that have been conceived by "natural cover" or "natural service" – the actual physical mating of a mare to a stallion – the Jockey Club being the most notable of these, as no artificial insemination is allowed in Thoroughbred breeding. Other registries such as the AQHA and warmblood registries allow registration of foals created through artificial insemination, and the process is widely used allowing the breeding of mares to stallions not resident at the same facility – or even in the same country – through the use of transported frozen or cooled semen.

In modern species conservation, semen collection and artificial insemination are used also in birds. In 2013 scientist of the Justus-Liebig-University of Giessen, Germany, from the working group of Michael Lierz, Clinic for birds, reptiles, amphibians, and fish, developed a novel technique for semen collection and artificial insemination in parrots producing the world's first macaw by assisted reproduction.

Scientists working with captive orcas were able to pioneer the technique in the early 2000s, resulting in "the first successful conceptions, resulting in live offspring, using artificial insemination in any cetacean species". John Hargrove, a SeaWorld trainer, describes Kasatka as being the first orca to receive artificial insemination.

Violation of rights

Main article: Animal rights

Artificial insemination on animals has been criticised as a violation of animal rights, with animal rights advocates equating it with rape and arguing it constitutes institutionalized bestiality. Artificial insemination of farm animals is condemned by animal rights campaigners such as People for the Ethical Treatment of Animals (PETA) and Joey Carbstrong, who identify the practice as a form of rape due to its sexual, involuntary and perceived painful nature. Animal rights organizations such as PETA and Mercy for Animals frequently write against the practice in their articles. Much of the meat production in the United States depends on artificial insemination, resulting in an explosive growth of the procedure over the past three decades. The state of Kansas makes no exceptions for artificial insemination under its bestiality law, thus making the procedure illegal.

Missile guidance

From Wikipedia, the free encyclopedia

For broader coverage of this topic, see Guidance system.

A guided bomb strikes a practice target

Missile guidance refers to several methods of guiding a missile or a guided bomb to its intended target. The missile's target accuracy is a critical factor for its effectiveness. Guidance systems improve missile accuracy by improving its Probability of Guidance (Pg).

These guidance technologies can generally be divided up into a number of categories, with the broadest categories being "active", "passive", and "preset" guidance. Missiles and guided bombs generally use similar types of guidance system, the difference between the two being that missiles are powered by an onboard engine, whereas guided bombs rely on the speed and height of the launch aircraft for propulsion.

History

The concept of unmanned guidance originated at least as early as World War I, with the idea of remotely guiding an airplane bomb onto a target, such as the systems developed for the first powered drones by Archibald Low (The Father of Radio Guidance).

In World War II, guided missiles were first developed, as part of the German V-weapons program. Project Pigeon was American behaviorist B.F. Skinner's attempt to develop a pigeon-guided bomb.

The first U.S. ballistic missile with a highly accurate inertial guidance system was the short-range PGM-11 Redstone.

Categories of guidance systems

Guidance systems are divided into different categories according to whether they are designed to attack fixed or moving targets. The weapons can be divided into two broad categories: Go-onto-target (GOT) and go-onto-location-in-space (GOLIS) guidance systems. A GOT missile can target either a moving or fixed target, whereas a GOLIS weapon is limited to a stationary or near-stationary target. The trajectory that a missile takes while attacking a moving target is dependent upon the movement of the target. A moving target can be an immediate threat to the missile launcher. The target must be promptly eliminated in order to preserve the launcher. In GOLIS systems, the problem is simpler because the target is not moving.

GOT systems

In every go-onto-target system there are three subsystems:

• Target tracker
• Missile tracker
• Guidance computer

The way these three subsystems are distributed between the missile and the launcher result in two different categories:

• Remote control guidance: The guidance computer is on the launcher. The target tracker is also placed on the launching platform.
• Homing guidance: The guidance computers are in the missile and in the target tracker.

Remote control guidance

These guidance systems usually need the use of radars and a radio or wired link between the control point and the missile; in other words, the trajectory is controlled with the information transmitted via radio or wire (see Wire-guided missile). These systems include:

• Command guidance – The missile tracker is on the launching platform. These missiles are fully controlled by the launching platform that sends all control orders to the missile. The two variants are

• Command to line-of-sight (CLOS)
• Command off line-of-sight (COLOS)

• Line-of-sight beam riding guidance (LOSBR) – The target tracker is on board the missile. The missile already has some orientation capability meant for flying inside the beam that the launching platform is using to illuminate the target. It can be manual or automatic.

Command to line-of-sight

The CLOS system uses only the angular coordinates between the missile and the target to ensure the collision. The missile is made to be in the line of sight between the launcher and the target (LOS), and any deviation of the missile from this line is corrected. Since so many types of missile use this guidance system, they are usually subdivided into four groups: A particular type of command guidance and navigation where the missile is always commanded to lie on the line of sight (LOS) between the tracking unit and the aircraft is known as command to line of sight (CLOS) or three-point guidance. That is, the missile is controlled to stay as close as possible on the LOS to the target after missile capture is used to transmit guidance signals from a ground controller to the missile. More specifically, if the beam acceleration is taken into account and added to the nominal acceleration generated by the beam-rider equations, then CLOS guidance results. Thus, the beam rider acceleration command is modified to include an extra term. The beam-riding performance described above can thus be significantly improved by taking the beam motion into account. CLOS guidance is used mostly in shortrange air defense and antitank systems.

Manual command to line-of-sight

Main article: Manual command to line of sight

Both target tracking and missile tracking and control are performed manually. The operator watches the missile flight, and uses a signaling system to command the missile back into the straight line between operator and target (the "line of sight"). This is typically useful only for slower targets, where significant "lead" is not required. MCLOS is a subtype of command guided systems. In the case of glide bombs or missiles against ships or the supersonic B-17 Flying Fortress against slow-moving B-17 Flying Fortress bombers this system worked, but as speeds increased MCLOS was quickly rendered useless for most roles.

Semi-manual command to line-of-sight

Target tracking is automatic, while missile tracking and control is manual.

Semi-automatic command to line-of-sight

Main article: Semi-automatic command to line of sight

Target tracking is manual, but missile tracking and control is automatic. It is similar to MCLOS but some automatic systems position the missile in the line of sight while the operator simply tracks the target. SACLOS has the advantage of allowing the missile to start in a position invisible to the user, as well as generally being considerably easier to operate. It is the most common form of guidance against ground targets such as tanks and bunkers.

Automatic command to line-of-sight

Target tracking, missile tracking and control are automatic.

Command off line-of-sight

This guidance system was one of the first to be used and still is in service, mainly in anti-aircraft missiles. In this system, the target tracker and the missile tracker can be oriented in different directions. The guidance system ensures the interception of the target by the missile by locating both in space. This means that they will not rely on the angular coordinates like in CLOS systems. They will need another coordinate which is distance. To make it possible, both target and missile trackers have to be active. They are always automatic and the radar has been used as the only sensor in these systems. The SM-2MR Standard is inertially guided during its mid-course phase, but it is assisted by a COLOS system via radar link provided by the AN/SPY-1 radar installed in the launching platform.

Line-of-sight beam riding guidance

Main article: Beam riding

LOSBR uses a "beam" of some sort, typically radio, radar or laser, which is pointed at the target and detectors on the rear of the missile keep it centered in the beam. Beam riding systems are often SACLOS, but do not have to be; in other systems the beam is part of an automated radar tracking system. A case in point is the later versions of the RIM-8 Talos missile as used in Vietnam – the radar beam was used to take the missile on a high arcing flight and then gradually brought down in the vertical plane of the target aircraft, the more accurate SARH homing being used at the last moment for the actual strike. This gave the enemy pilot the least possible warning that his aircraft was being illuminated by missile guidance radar, as opposed to search radar. This is an important distinction, as the nature of the signal differs, and is used as a cue for evasive action.

LOSBR suffers from the inherent weakness of inaccuracy with increasing range as the beam spreads out. Laser beam riders are more accurate in this regards, but are all short-range, and even the laser can be degraded by bad weather. On the other hand, SARH becomes more accurate with decreasing distance to the target, so the two systems are complementary.

Homing guidance

Proportional navigation

Main article: Proportional navigation

Proportional navigation (also known as "PN" or "Pro-Nav") is a guidance principle (analogous to proportional control) used in some form or another by most homing air target missiles. It is based on the fact that two objects are on a collision course when the direction of their direct line-of-sight does not change. PN dictates that the missile velocity vector should rotate at a rate proportional to the rotation rate of the line of sight (line-Of-sight rate or LOS-rate) and in the same direction.

Radar homing

Active homing

Main article: active radar homing

Active homing uses a radar system on the missile to provide a guidance signal. Typically, electronics in the missile keep the radar pointed directly at the target, and the missile then looks at this "angle" of its own centerline to guide itself. Radar resolution is based on the size of the antenna, so in a smaller missile these systems are useful for attacking only large targets, ships or large bombers for instance. Active radar systems remain in widespread use in anti-shipping missiles, and in "fire-and-forget" air-to-air missile systems such as the AIM-120 AMRAAM and R-77.

Semi-active homing

Main article: Semi-active radar homing

Semi-active homing systems combine a passive radar receiver on the missile with a separate targeting radar that "illuminates" the target. Since the missile is typically being launched after the target was detected using a powerful radar system, it makes sense to use that same radar system to track the target, thereby avoiding problems with resolution or power, and reducing the weight of the missile. Semi-active radar homing (SARH) is by far the most common "all weather" guidance solution for anti-aircraft systems, both ground- and air-launched.

It has the disadvantage for air-launched systems that the launch aircraft must keep moving towards the target in order to maintain radar and guidance lock. This has the potential to bring the aircraft within range of shorter-ranged IR-guided (infrared-guided) missile systems. It is an important consideration now that "all aspect" IR missiles are capable of "kills" from head on, something which did not prevail in the early days of guided missiles. For ships and mobile or fixed ground-based systems, this is irrelevant as the speed (and often size) of the launch platform precludes "running away" from the target or opening the range so as to make the enemy attack fail.

SALH is similar to SARH but uses a laser as a signal. Another difference is that most laser-guided weapons employ turret-mounted laser designators which increase the launching aircraft's ability to maneuver after launch. How much maneuvering can be done by the guiding aircraft depends on the turret field of view and the system's ability to maintain a lock-on while maneuvering. As most air-launched, laser-guided munitions are employed against surface targets the designator providing the guidance to the missile need not be the launching aircraft; designation can be provided by another aircraft or by a completely separate source (frequently troops on the ground equipped with the appropriate laser designator).

Passive homing

See also: passive radar and anti-radiation missile

Infrared homing is a passive system that homes in on the heat generated by the target. Typically used in the anti-aircraft role to track the heat of jet engines, it has also been used in the anti-vehicle role with some success. This means of guidance is sometimes also referred to as "heat seeking".

Contrast seekers use a video camera, typically black and white, to image a field of view in front of the missile, which is presented to the operator. When launched, the electronics in the missile look for the spot on the image where the contrast changes the fastest, both vertically and horizontally, and then attempts to keep that spot at a constant location in its view. Contrast seekers have been used for air-to-ground missiles, including the AGM-65 Maverick, because most ground targets can be distinguished only by visual means. However they rely on there being strong contrast changes to track, and even traditional camouflage can render them unable to "lock on".

Retransmission homing

Main article: Track-via-missile

Retransmission homing, also called "track-via-missile" or "TVM", is a hybrid between command guidance, semi-active radar homing and active radar homing. The missile picks up radiation broadcast by the tracking radar which bounces off the target and relays it to the tracking station, which relays commands back to the missile.

AI guidance

Main article: Artificial intelligence arms race

In 2017, Russian weapons manufacturer Tactical Missiles Corporation announced that it was developing missiles that would use artificial intelligence to choose their own targets. In 2019, the United States Army announced it was developing a similar technology.

GOLIS systems

Israel's Arrow 3 missiles use a gimbaled seeker for hemispheric coverage. By measuring the seeker's line-of-sight propagation relative to the vehicle's motion, they use proportional navigation to divert their course and line up exactly with the target's flight path.

Whatever the mechanism used in a go-onto-location-in-space guidance system is, it must contain preset information about the target. These systems' main characteristic is the lack of a target tracker. The guidance computer and the missile tracker are located in the missile. The lack of target tracking in GOLIS necessarily implies navigational guidance.

Navigational guidance is any type of guidance executed by a system without a target tracker. The other two units are on board the missile. These systems are also known as self-contained guidance systems; however, they are not always entirely autonomous due to the missile trackers used. They are subdivided by their missile tracker's function as follows:

• Entirely autonomous – Systems where the missile tracker does not depend on any external navigation source, and can be divided into:

• Inertial guidance

• With a gimballed gyrostabilized platform or fluid-suspended gyrostabilized platform
• With strapdown inertial guidance

• Preset guidance

• Dependent on natural sources – Navigational guidance systems where the missile tracker depends on a natural external source:

• Celestial guidance
• Astro-inertial guidance
• Terrestrial guidance

• Topographic reconnaissance (Ex: TERCOM)
• Photographic reconnaissance (Ex: DSMAC)

• Magnetic guidance

• Dependent on artificial sources – Navigational guidance systems where the missile tracker depends on an artificial external source:

• Satellite navigation

• Global positioning system (GPS)
• Global navigation satellite system (GLONASS)

• Hyperbolic navigation

• DECCA
• LORAN C

Preset guidance

Preset guidance is the simplest type of missile guidance. From the distance and direction of the target, the trajectory of the flight path is determined. Before firing, this information is programmed into the missile's guidance system, which, during flight, maneuvers the missile to follow that path. All of the guidance components (including sensors such as accelerometers or gyroscopes) are contained within the missile, and no outside information (such as radio instructions) is used. An example of a missile using preset guidance is the V-2 rocket.

Inertial guidance

Main article: Inertial guidance

Inspection of MM III missile guidance system

Inertial guidance uses sensitive measurement devices to calculate the location of the missile due to the acceleration put on it after leaving a known position. Early mechanical systems were not very accurate, and required some sort of external adjustment to allow them to hit targets even the size of a city. Modern systems use solid state ring laser gyros that are accurate to within metres over ranges of 10,000 km, and no longer require additional inputs. Gyroscope development has culminated in the AIRS found on the MX missile, allowing for an accuracy of less than 100 m at intercontinental ranges. Many civilian aircraft use inertial guidance using a ring laser gyroscope, which is less accurate than the mechanical systems found in ICBMs, but which provide an inexpensive means of attaining a fairly accurate fix on location (when most airliners such as Boeing's 707 and 747 were designed, GPS was not the widely commercially available means of tracking that it is today). Today guided weapons can use a combination of INS, GPS and radar terrain mapping to achieve extremely high levels of accuracy such as that found in modern cruise missiles.

Inertial guidance is most favored for the initial guidance and reentry vehicles of strategic missiles, because it has no external signal and cannot be jammed. Additionally, the relatively low precision of this guidance method is less of an issue for large nuclear warheads.

Astro-inertial guidance

See also: Inertial navigation system and Celestial navigation

Astro-inertial guidance is a sensor fusion-information fusion of inertial guidance and celestial navigation. It is usually employed on submarine-launched ballistic missiles. Unlike silo-based intercontinental ballistic missiles, whose launch point does not move and thus can serve as a reference, SLBMs are launched from moving submarines, which complicates the necessary navigational calculations and increases circular error probable. This stellar-inertial guidance is used to correct small position and velocity errors that result from launch condition uncertainties due to errors in the submarine navigation system and errors that may have accumulated in the guidance system during the flight due to imperfect instrument calibration.

The USAF sought a precision navigation system for maintaining route accuracy and target tracking at very high speeds. Nortronics, Northrop's electronics development division, had developed an astro-inertial navigation system (ANS), which could correct inertial navigation errors with celestial observations, for the SM-62 Snark missile, and a separate system for the ill-fated AGM-48 Skybolt missile, the latter of which was adapted for the SR-71.

It uses star positioning to fine-tune the accuracy of the inertial guidance system after launch. As the accuracy of a missile is dependent upon the guidance system knowing the exact position of the missile at any given moment during its flight, the fact that stars are a fixed reference point from which to calculate that position makes this a potentially very effective means of improving accuracy.

In the Trident missile system this was achieved by a single camera that was trained to spot just one star in its expected position (it is believed^[who?] that the missiles from Soviet submarines would track two separate stars to achieve this), if it was not quite aligned to where it should be then this would indicate that the inertial system was not precisely on target and a correction would be made.

Terrestrial guidance

Main articles: TERCOM and TERCOM § DSMAC

TERCOM, for "terrain contour matching", uses altitude maps of the strip of land from the launch site to the target, and compares them with information from a radar altimeter on board. More sophisticated TERCOM systems allow the missile to fly a complex route over a full 3D map, instead of flying directly to the target. TERCOM is the typical system for cruise missile guidance, but is being supplanted by GPS systems and by DSMAC, digital scene-matching area correlator, which employs a camera to view an area of land, digitizes the view, and compares it to stored scenes in an onboard computer to guide the missile to its target.

DSMAC is reputed to be so lacking in robustness that destruction of prominent buildings marked in the system's internal map (such as by a preceding cruise missile) upsets its navigation.

Vasodilation

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Vasodilation

3D Medical animation still showing normal blood vessel (L) vs. vasodilation (R)

Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, which is the narrowing of blood vessels.

When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance and increase in cardiac output. Therefore, dilation of arterial blood vessels (mainly the arterioles) decreases blood pressure. The response may be intrinsic (due to local processes in the surrounding tissue) or extrinsic (due to hormones or the nervous system). In addition, the response may be localized to a specific organ (depending on the metabolic needs of a particular tissue, as during strenuous exercise), or it may be systemic (seen throughout the entire systemic circulation).

Endogenous substances and drugs that cause vasodilation are termed vasodilators. Such vasoactivity is necessary for homeostasis (keeping the body running normally).

Function

The primary function of vasodilation is to increase blood flow in the body to tissues that need it most. This is often in response to a localized need for oxygen but can occur when the tissue in question is not receiving enough glucose, lipids, or other nutrients. Localized tissues have multiple ways to increase blood flow, including releasing vasodilators, primarily adenosine, into the local interstitial fluid, which diffuses to capillary beds, provoking local vasodilation. Some physiologists have suggested that it is the lack of oxygen itself that causes capillary beds to vasodilate by the smooth muscle hypoxia of the vessels in the region. This latter hypothesis is posited due to the presence of precapillary sphincters in capillary beds. These approaches to the mechanism of vasodilation are not mutually exclusive.

Vasodilation and arterial resistance

Vasodilation directly affects the relationship between mean arterial pressure, cardiac output, and total peripheral resistance (TPR). Vasodilation occurs in the time phase of cardiac systole, whereas vasoconstriction follows in the opposite time phase of cardiac diastole. Cardiac output (blood flow measured in volume per unit time) is computed by multiplying the heart rate (in beats per minute) and the stroke volume (the volume of blood ejected during ventricular systole). TPR depends on several factors, including the length of the vessel, the viscosity of blood (determined by hematocrit) and the diameter of the blood vessel. The latter is the most important variable in determining resistance, with the TPR changing by the fourth power of the radius. An increase in either of these physiological components (cardiac output or TPR) causes a rise in the mean arterial pressure. Vasodilation works to decrease TPR and blood pressure through relaxation of smooth muscle cells in the tunica media layer of large arteries and smaller arterioles.

Vasodilation occurs in superficial blood vessels of warm-blooded animals when their ambient environment is hot; this process diverts the flow of heated blood to the skin of the animal, where heat can be more easily released to the environment. The opposite physiological process is vasoconstriction. These processes are naturally modulated by local paracrine agents from endothelial cells (e.g., nitric oxide, bradykinin, potassium ions, and adenosine), and by the autonomic nervous system and the adrenal glands, both of which secrete catecholamines, such as norepinephrine and epinephrine, respectively.

Examples and individual mechanisms

Vasodilation is the result of relaxation in smooth muscle surrounding the blood vessels. This relaxation, in turn, relies on removing the stimulus for contraction, which depends on intracellular calcium ion concentrations and is tightly linked with phosphorylation of the light chain of the contractile protein myosin. Thus, vasodilation works mainly either by lowering intracellular calcium concentration or by dephosphorylation (really substitution of ATP for ADP) of myosin. Dephosphorylation by myosin light-chain phosphatase and induction of calcium symporters and antiporters that pump calcium ions out of the intracellular compartment both contribute to smooth muscle cell relaxation and therefore vasodilation. This is accomplished through reuptake of ions into the sarcoplasmic reticulum via exchangers and expulsion across the plasma membrane. There are three main intracellular stimuli that can result in the vasodilation of blood vessels. The specific mechanisms to accomplish these effects vary from vasodilator to vasodilator.

Class	Description	Example
Hyperpolarization-mediated (Calcium channel blocker)	Changes in the resting membrane potential of the cell affects the level of intracellular calcium through modulation of voltage-sensitive calcium channels in the plasma membrane.	adenosine
cAMP-mediated	Adrenergic stimulation results in elevated levels of cAMP and protein kinase A, which results in increasing calcium removal from the cytoplasm.	prostacyclin
cGMP-mediated (Nitrovasodilator)	Through stimulation of protein kinase G.	nitric oxide

PDE5 inhibitors and potassium channel openers can also have similar results.

Compounds that mediate the above mechanisms may be grouped as endogenous and exogenous.

Endogenous

The vasodilating action of activation of beta-2 receptors (such as by adrenaline) appears to be endothelium-independent.

Sympathetic nervous system vasodilation

Although it is recognized that the sympathetic nervous system plays an expendable role in vasodilation, it is only one of the mechanisms by which vasodilation can be accomplished. The spinal cord has both vasodilation and vasoconstriction nerves. The neurons that control vascular vasodilation originate in the hypothalamus. Some sympathetic stimulation of arterioles in skeletal muscle is mediated by epinephrine acting on β-adrenergic receptors of arteriolar smooth muscle, which would be mediated by cAMP pathways, as discussed above. However, it has been shown that knocking out this sympathetic stimulation plays little or no role in whether skeletal muscle is able to receive sufficient oxygen even at high levels of exertion, so it is believed that this particular method of vasodilation is of little importance to human physiology.

In cases of emotional distress, this system may activate, resulting in fainting due to decreased blood pressure from vasodilation, which is referred to as vasovagal syncope.

Cold-induced vasodilation

Cold-induced vasodilation (CIVD) occurs after cold exposure, possibly to reduce the risk of injury. It can take place in several locations in the human body but is observed most often in the extremities. The fingers are especially common because they are exposed most often.

When the fingers are exposed to cold, vasoconstriction occurs first to reduce heat loss, resulting in strong cooling of the fingers. Approximately five to ten minutes after the start of the cold exposure of the hand, the blood vessels in the finger tips will suddenly vasodilate. This is probably caused by a sudden decrease in the release of neurotransmitters from the sympathetic nerves to the muscular coat of the arteriovenous anastomoses due to local cold. The CIVD increases blood flow and subsequently the temperature of the fingers. This can be painful and is sometimes known as the 'hot aches' which can be painful enough to bring on vomiting.

A new phase of vasoconstriction follows the vasodilation, after which the process repeats itself. This is called the Hunting reaction. Experiments have shown that three other vascular responses to immersion of the finger in cold water are possible: a continuous state of vasoconstriction; slow, steady, and continuous rewarming; and a proportional control form in which the blood vessel diameter remains constant after an initial phase of vasoconstriction. However, the vast majority of responses can be classified as the Hunting reaction.

Other possible causes of vasodilation

Other suggested vasodilators or vasodilating factors include:

• absence of high levels of environmental noise
• absence of high levels of illumination
• adenosine - adenosine agonist, used primarily as an anti-arrhythmic
• alpha blockers (block the vasoconstricting effect of adrenaline)
• amyl nitrite and other nitrites are often used recreationally as a vasodilator, causing lightheadedness and a euphoric feeling
• atrial natriuretic peptide (ANP) - a weak vasodilator
• capsaicin (chili)
• ethanol (alcohol)
• histamine-inducers
  • Complement proteins C3a, C4a, and C5a work by triggering histamine release from mast cells and basophil granulocytes.
• nitric oxide inducers
  • l-arginine (a key amino acid)
  • glyceryl trinitrate (commonly known as nitroglycerin)
  • isosorbide mononitrate and isosorbide dinitrate
  • pentaerythritol tetranitrate (PETN)
  • sodium nitroprusside
  • PDE5 inhibitors: these agents indirectly increase the effects of nitric oxide
    • sildenafil (Viagra)
    • tadalafil (Cialis)
    • vardenafil (Levitra)
• tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis.
• theobromine, the principal alkaloid found in Theobroma cacao, specifically in cocoa solids (which is found in chocolate, especially dark chocolate).
• minoxidil
• papaverine an alkaloid found in the opium poppy papaver somniferum
• estrogen
• apigenin: In rat small mesenteric arteries, apigenin acts on TRPV4 in endothelial cells to induce EDHF-mediated vascular dilation (Br J Pharmacol 2011 Nov 3)

Therapeutic uses

Vasodilators are used to treat conditions such as hypertension, wherein the patient has an abnormally high blood pressure, as well as angina, congestive heart failure, and erectile dysfunction, and where maintaining a lower blood pressure reduces the patient's risk of developing other cardiac problems. Flushing may be a physiological response to vasodilators. Some phosphodiesterase inhibitors such as sildenafil, vardenafil and tadalafil, work to increase blood flow in the penis through vasodilation. They may also be used to treat pulmonary arterial hypertension (PAH).

Antihypertensives that work by opening blood vessels

These drugs can keep vessels staying opened or help vessels refrain from being narrowed.

• Angiotensin II receptor blockers
• ACE inhibitors
• Calcium channel blockers

Drugs that appear to work by activating the α_2A receptors in the brain thereby decreasing sympathetic nervous system activity.

• methyldopa

According to American Heart Association, Alpha-methyldopa may cause Orthostatic syncope as it exerts a greater blood pressure lowering effect when one is standing upright which may lead to feeling weak or fainting if the blood pressure has been lowered too far. Methyldopa's prominent side effects include drowsiness or sluggishness, dryness of the mouth, fever or anemia. Additionally to these, male patients may experience impotence.

• clonidine hydrochloride
• guanabenz acetate
• guanfacine hydrochloride

Clonidine, guanabenz or guanfacine may give rise to severe dryness of the mouth, constipation or drowsiness. Abrupt cessation taking may raise blood pressure quickly to dangerously high levels.

Directly relax the muscle in the walls of the blood vessels (especially the arterioles), allowing the vessel to dilate (widen).

• hydralazine
• minoxidil

Hydralazine may cause headaches, swelling around the eyes, heart palpitations or aches and pains in the joints. In clinical setting, hydralazine isn't usually used alone.

Minoxidil is a potent direct vasodilator used only in resistant severe high blood pressure or when kidney failure is present. Noted adverse effects comprise fluid retention (marked weight gain) and excessive hair growth.