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. 1978 Jul;63(3):541–549. doi: 10.1111/j.1476-5381.1978.tb07810.x

The Effect of Ergotamine on Tissue Blood Flow and the Arteriovenous Shunting of Radioactive Microspheres in the Head

Barbara M Johnston, PR Saxena
PMCID: PMC1668089  PMID: 667498

Abstract

1 The radioactive microsphere method was used to study the effects of ergotamine (5, 10 and 20 μg/kg, i.v.) on systemic and regional haemodynamic variables in chloralose-urethane anaesthetized cats. The influence of the drug was also studied on the number of 15 μm microspheres escaping entrapment in the head to emerge in the left external jugular vein.

2 Ergotamine decreased the heart rate and cardiac output. Since arterial blood pressure remained unchanged, calculated total peripheral resistance increased.

3 The regional distribution of cardiac output obtained with 15 μm microspheres agreed well with previous studies in cats where 25 μm spheres were used. The most pronounced difference was that in the present investigation more microspheres, apparently escaping through arteriovenous anastomoses (AVAs), were detected in the lungs than when larger spheres had been used.

4 Coronary blood flow decreased, while uterine blood flow was increased by the drug. The microsphere content of the lungs, which receive the spheres not only via bronchial arteries but also via AVAs, was greatly reduced by all doses of ergotamine. Ergotamine did not influence tissue blood flow to other major organs such as the brain, kidneys, skin, liver, skeletal muscle or the gastrointestinal tract.

5 In the 16 experiments, 0.46 ± 0.05 (s.e. mean)% of the total microspheres injected (equivalent to 11.7 ± 1.4% of microspheres detected in the left-side of the head) appeared within 2 min of microsphere injection into the left external jugular vein. The highest dose of ergotamine significantly reduced the shunting of the microspheres in the head.

6 Since 15 μm microspheres are only likely to reach the lungs by passing into the venous circulation through large glomus-type AVAs, we conclude that ergotamine reduces the fraction of microspheres appearing in the lungs by causing strong vasoconstriction in the AVAs in the head.

7 In conformity with the closure of head AVAs is the finding that ergotamine reduced the jugular venous Po2 and O2 saturation thereby increasing the A-V O2 saturation difference.

8 It is quite possible that decreased A-V shunting may be the prominent mechanism of the antimigraine action of the drug, since sudden opening of AVA's has been implicated in the pathophysiology of migraine-syndrome.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alm A. Radioactively labelled microspheres in regional cerebral blood flow determinations. A study on monkeys with 15 and 35 mum spheres. Acta Physiol Scand. 1975 Sep;95(1):60–65. doi: 10.1111/j.1748-1716.1975.tb10025.x. [DOI] [PubMed] [Google Scholar]
  2. Archie J. P., Jr, Fixler D. E., Ullyot D. J., Hoffman J. I., Utley J. R., Carlson E. L. Measurement of cardiac output with and organ trapping of radioactive microspheres. J Appl Physiol. 1973 Jul;35(1):148–154. doi: 10.1152/jappl.1973.35.1.148. [DOI] [PubMed] [Google Scholar]
  3. BURTON A. C. Relation of structure to function of the tissues of the wall of blood vessels. Physiol Rev. 1954 Oct;34(4):619–642. doi: 10.1152/physrev.1954.34.4.619. [DOI] [PubMed] [Google Scholar]
  4. Creasy R. K., Kahanpä K. V., De Swiet M. Trapping of radioactive microspheres in the pregnant and non-pregnant rabbit. Acta Physiol Scand. 1974 Jan;90(1):252–259. doi: 10.1111/j.1748-1716.1974.tb05584.x. [DOI] [PubMed] [Google Scholar]
  5. DANIEL P. M., PRICHARD M. M. Arteriovenous anastomoses in the external ear. Q J Exp Physiol Cogn Med Sci. 1956 Apr;41(2):107–123. doi: 10.1113/expphysiol.1956.sp001169. [DOI] [PubMed] [Google Scholar]
  6. Forsyth R. P., Nies A. S., Wyler F., Neutze J., Melmon K. L. Normal distribution of cardiac output in the unanesthetized, restrined rhesus monkey. J Appl Physiol. 1968 Dec;25(6):736–741. doi: 10.1152/jappl.1968.25.6.736. [DOI] [PubMed] [Google Scholar]
  7. GILLILAN L. A., MARKESBERY W. R. ARTERIOVENOUS SHUNTS IN THE BLOOD SUPPLY TO THE BRAINS OF SOME COMMON LABORATORY ANIMALS--WITH SPECIAL ATTENTION TO THE RETE MIRABILE CONJUGATUM IN THE CAT. J Comp Neurol. 1963 Dec;121:305–311. doi: 10.1002/cne.901210302. [DOI] [PubMed] [Google Scholar]
  8. HADDY F. J. Serotonin and the vascular system. Angiology. 1960 Feb;11:21–24. doi: 10.1177/000331976001100104. [DOI] [PubMed] [Google Scholar]
  9. Hales J. R. Chronic catheterization for sampling venous blood from the brain of the sheep. Pflugers Arch. 1972;337(1):81–85. doi: 10.1007/BF00587875. [DOI] [PubMed] [Google Scholar]
  10. Heymann M. A., Payne B. D., Hoffman J. I., Rudolph A. M. Blood flow measurements with radionuclide-labeled particles. Prog Cardiovasc Dis. 1977 Jul-Aug;20(1):55–79. doi: 10.1016/s0033-0620(77)80005-4. [DOI] [PubMed] [Google Scholar]
  11. Johnston B. M., Owen D. A. Tissue blood flow and distribution of cardiac output in cats: changes caused by intravenous infusions of histamine and histamine receptor agonists. Br J Pharmacol. 1977 Jun;60(2):173–180. doi: 10.1111/j.1476-5381.1977.tb07738.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KLEINMAN L. I., RADFORD E. P., Jr VENTILATION STANDARDS FOR SMALL MAMMALS. J Appl Physiol. 1964 Mar;19:360–362. doi: 10.1152/jappl.1964.19.2.360. [DOI] [PubMed] [Google Scholar]
  13. Langer S. Z. Sixth gaddum memorial lecture, National Institute for Medical Research, Mill Hill, January 1977. Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol. 1977 Aug;60(4):481–497. doi: 10.1111/j.1476-5381.1977.tb07526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lopez-Majano V., Migita T., Rhodes B. A., Bardfeld P., Wagner H. N., Jr Distribution of the carotid circulation in dog. Cor Vasa. 1971;13(1):71–76. [PubMed] [Google Scholar]
  15. Marcus M. L., Heistad D. D., Ehrhardt J. C., Abboud F. M. Total and regional cerebral blood flow measurement with 7-10-, 15-, 25-, and 50-mum microspheres. J Appl Physiol. 1976 Apr;40(4):501–507. doi: 10.1152/jappl.1976.40.4.501. [DOI] [PubMed] [Google Scholar]
  16. Müller-Schweinitzer E., Stürmer E. Investigations on the mode of action of ergotamine in the isolated femoral vein of the dog. Br J Pharmacol. 1974 Jul;51(3):441–446. doi: 10.1111/j.1476-5381.1974.tb10680.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. ROWBOTHAM G. F., LITTLE E. NEW CONCEPTS ON THE AETIOLOGY AND VASCULARIZATION OF MENINGIOMATA; THE MECHANISM OF MIGRAINE; THE CHEMICAL PROCESSES OF THE CEREBROSPINAL FLUID; AND THE FORMATION OF COLLECTIONS OF BLOOD OR FLUID IN THE SUBDURAL SPACE. Br J Surg. 1965 Jan;52:21–24. doi: 10.1002/bjs.1800520105. [DOI] [PubMed] [Google Scholar]
  18. Rudolph A. M., Heymann M. A. The circulation of the fetus in utero. Methods for studying distribution of blood flow, cardiac output and organ blood flow. Circ Res. 1967 Aug;21(2):163–184. doi: 10.1161/01.res.21.2.163. [DOI] [PubMed] [Google Scholar]
  19. SHERMAN J. L., Jr NORMAL ARTERIOVENOUS ANASTOMOSES. Medicine (Baltimore) 1963 Jul;42:247–267. doi: 10.1097/00005792-196307000-00001. [DOI] [PubMed] [Google Scholar]
  20. Slotkoff L. M., Logan A., Jose P., D'Avella J., Eisner G. M. Microsphere measurement of intrarenal circulation of the dog. Circ Res. 1971 Feb;28(2):158–166. doi: 10.1161/01.res.28.2.158. [DOI] [PubMed] [Google Scholar]
  21. Somerville B. W. Platelet-bound and free serotonin levels in jugular and forearm venous blood during migraine. Neurology. 1976 Jan;26(1):41–45. doi: 10.1212/wnl.26.1.41. [DOI] [PubMed] [Google Scholar]
  22. Spence R. J., Rhodes B. A., Wagner H. N., Jr Regulation of arteriovenous anastomotic and capillary blood flow in the dog leg. Am J Physiol. 1972 Feb;222(2):326–332. doi: 10.1152/ajplegacy.1972.222.2.326. [DOI] [PubMed] [Google Scholar]
  23. Toda N., Fujita Y. Responsiveness of isolated cerebral and peripheral arteries to serotonin, norepinephrine, and transmural electrical stimulation. Circ Res. 1973 Jul;33(1):98–104. doi: 10.1161/01.res.33.1.98. [DOI] [PubMed] [Google Scholar]
  24. Warren D. J., Ledingham J. G. Measurement of cardiac output distribution using microspheres. Some practical and theoretical considerations. Cardiovasc Res. 1974 Jul;8(4):570–581. doi: 10.1093/cvr/8.4.570. [DOI] [PubMed] [Google Scholar]
  25. Wellens D., Szigetvari E., Wauters E. Reflex vasodilation, ergotamine and uptake of circulating norepinephrine. Arch Int Pharmacodyn Ther. 1970 Feb;183(2):412–415. [PubMed] [Google Scholar]
  26. Zanick D. C., Delaney J. P. Temperature influences on arteriovenous anastomoses. Proc Soc Exp Biol Med. 1973 Nov;144(2):616–620. doi: 10.3181/00379727-144-37646. [DOI] [PubMed] [Google Scholar]
  27. Zinner M. J., Kerr J. C., Reynolds D. G. Distribution and arteriovenous shunting of gastric blood flow in the baboon: effect of epinephrine and vasopressin infusions. Gastroenterology. 1976 Aug;71(2):299–302. [PubMed] [Google Scholar]

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