Ductus arteriosus

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Ductus arteriosus
Gray502.png
Plan of the fetal circulation. ("Ductus arteriosus" visible at upper right.)
Patent ductus arteriosus.svg
Heart cross-section with PDA
Details
Latin Ductus arteriosus
Source
pulmonary artery
Branches
descending aorta
ductus venosus
aortic arch 6
Identifiers
Gray's p.540
MeSH A07.541.278.395
Dorlands
/Elsevier
d_29/12314749
Anatomical terminology

In the developing fetus, the ductus arteriosus (DA), also called the ductus Botalli, is a blood vessel connecting the pulmonary artery to the proximal descending aorta. It allows most of the blood from the right ventricle to bypass the fetus's fluid-filled non-functioning lungs. Upon closure at birth, it becomes the ligamentum arteriosum. There are two other fetal shunts, the ductus venosus and the foramen ovale.

Clinical significance[edit]

Patent ductus arteriosus[edit]

Failure of a child's DA to close after birth results in a condition called patent ductus arteriosus and the generation of a left-to-right shunt. If left uncorrected, patency leads to pulmonary hypertension and possibly congestive heart failure and cardiac arrhythmias. Prostaglandins are responsible for maintaining the ductus arteriosus by dilation of the vascular smooth muscles.

The E series of prostaglandins are responsible for maintaining the patency of the ductus arterisus (DA) throughout the fetal period.[1] Prostaglandin E2 (PGE2), produced by both the placenta and the DA itself, is by far the most potent of the E prostaglandins, but prostaglandin E1 (PGE1) also has a role in keeping the ductus arteriosus open.[2] PGE1 and PGE2 keep the ductus open by increasing the concentration of intracellular cAMP, and by using specific receptors such as EP2 or EP4 which are sensitive to PGE2.[3] EP4 is the major receptor associated with PGE2-induced dilation of the DA and can be found all over the ductus arteriosus in the smooth muscle cells.[4] EP2 is also found here, but at lower levels.[5] After being activated by PGE2, the stimulatory G proteins, G3 that are coupled with the EP2 and EP4 receptors are activated.[6] The G3α subunit activates adenylyl cyclase, which in turn produces cAMP (7). Increased cAMP inhibits myosin light chain kinase, preventing the phosphorylation of myosin light chain, leading to relaxation of the smooth muscle surrounding the DA.[7] Throughout pregnancy the DA of the fetus remains open, due prostaglandins, but immediately after birth the levels of both PGE2 and the EP4 receptors will reduce significantly.[8] This allows the ductus arteriosus to close, so that the normal post-natal circulation of the heart can commence. If the child has certain congenital heart defects such as Transposition of the great arteries, they may have prostaglandins administered to them to maintain the patency of the ductus arteriosus until surgery can be performed.[9] This is necessary, so that the blood can continue to circulate and become oxygenated, until the congenital defect can be corrected.

Closure may be induced with NSAIDs because these drugs inhibit prostaglandin synthesis. The ductus arterisous may remain patent after birth. In this case non steroidal anti-inflammatory drugs (NSAIDs) will be used to close the DA.[10] Prostaglandins are formed when arachadonic acid is cleaved from the phospholipid membrane of a cell and broken down.[11] The enzyme that is responsible for the breakdown of arachodonic acid is cyclooxygenase.[12] NSAIDs inhibit prostaglandin synthesis by acting directly on cyclooxygenase, preventing the breakdown of arachadonic acid to prostaglandins.[13] The most common NSAID that is used to force DA closure is Indomethacin, which can be administered after birth.[14] By inhibiting the formation of PGE2, the ability to activate EP4 receptors and therefore the ability to increase the concentration of cAMP will be decreased, and normal circulation can begin. NSAIDs taken late in a pregnancy can cross the placenta and lead to premature closure of the DA in the fetus.[15] If this were to happen, exogenous PDE2 can be administered to reverse the effects of the NSAIDs and maintain the patency of the DA for the remainder of the pregnancy.[16]

A patent ductus arteriosus affects around 4% of infants with Down syndrome (DS). A failure to thrive is a very common sign of this condition.[17]

See also[edit]

This article uses anatomical terminology; for an overview, see anatomical terminology.

References[edit]

  1. ^ "Prostaglandins and the ductus arteriosus". The Lancet. 
  2. ^ Olley, P.M.; Conceani F. (1981). Annual Review of Medicine 32 (1): 375–385 http://journals1.scholarsportal.info.subzero.lib.uoguelph.ca/pdf/00664219/v32i0001/375_patda.xml |url= missing title (help). 
  3. ^ Bouayad, D.R.; Kajini W., Waleh N., Fouron J. Andelfinger A., Vazquez A., Gobeil F., Clyman R., Chemtob S. (1 May 2001). "Characterization of PGE2 Receptors in fetal and newborn lamb ductus arteriosus". American Journal of Physiology- Heart and Circulatory Physiology 280 (5): 2342–2349. 
  4. ^ Gruzdeva, A; Nguyena, M.; Kovarovob, M.; Koller, B (March 2012). "PGE2 through the EP4 receptor controls smooth muscle gene expression patterns in the ductus arteriosus critical for remodeling at birth.". Prostaglandins and other Lipid Mediators 94 (3): 109–119. 
  5. ^ Gruzdeva, A.; Nguyena, M.; Kovarovob, M.; Koller, B (March 2012). "PGE2 through the EP4 receptor controls smooth muscle gene expression patterns in the ductus arteriosus critical for remodeling at birth". Prostaglandins and other Lipid Mediators 94 (3): 109–119. 
  6. ^ Gruzdeva, A.; Nguyena, M.; Kovarovob, M.; Koller, B (March 2012). "PGE2 through the EP4 receptor controls smooth muscle gene expression patterns in the ductus arteriosus critical for remodeling at birth.". Prostaglandins and other Lipid Mediators 94 (3): 109–119. 
  7. ^ Zelis, R (27 June 1983). "Mechanisms of Vasodilation". The American Journal of Medicine 74 (6): 3–12. doi:10.1016/0002-9343(83)90848-3. 
  8. ^ Gruzdeva, A.; Nguyena, M.; Kovarovob, M.; Koller, B. (March 2012). "PGE2 through the EP4 receptor controls smooth muscle gene expression patterns in the ductus arteriosus critical for remodeling at birth.". Prostaglandins and other Lipid Mediators 94 (3): 109–119. 
  9. ^ "Congenital heart defects: Prostaglandins and prostaglandin inhibitors.". Healthwise. My Health Alberta. 
  10. ^ Olley, P.M.; COnceani F. (1981). "Prostaglandins and the ductus arteriosus". Annual Review of Medicine 32 (1): 375–385. doi:10.1146/annurev.me.32.020181.002111. 
  11. ^ Robinson, D.R. (31 October 1983). "Prostaglandins and the mechanism of action of anti-inflammatory drugs". The American Journal of Medicine 75 (4): 26–31. doi:10.1016/0002-9343(83)90325-x. 
  12. ^ Robinson, D.R. (31 October 1983). "Prostaglandins and the mechanism of action of anti-inflammatory drugs.". The American Journal of Medicine 75 (4): 26–31. doi:10.1016/0002-9343(83)90325-x. 
  13. ^ Robinson, D.R (31 October 1983). "Prostaglandins and the mechanism of action of anti-inflammatory drugs.". The American Journal of Medicine 74 (4): 26–31. 
  14. ^ Olley, P.M; Conceani F. (1981). "Prostaglandins and the ductus arteriosus". Review of Medicine 32 (1): 375–385. doi:10.1146/annurev.me.32.020181.002111. 
  15. ^ Anonucci, R; Zaffanello, M.; Puxeddu, E.; Porcella, A.; Cuzzolin, L.; Pilloni, M.; Fanos, V. (2012). "Use of non-steroidal anti-inflammatory drugs in pregnancy:impact on the fetus and newborn". Current Drug Metabolism 13 (4): 474–490. doi:10.2174/138920012800166607. 
  16. ^ Olley, P.M; Conceani F. (1981). "Prostaglandins and the ductus arteriosus". Annual Review of Medicine 32 (1): 375–385. doi:10.1146/annurev.me.32.020181.002111. 
  17. ^ Pritchard & Korf. "Medical Genetics at a Glance". Blackwell Publishing. 2010. p63.

External links[edit]