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. 1975 Jun;55(6):1219–1228. doi: 10.1172/JCI108040

Effects of nitroglycerin on transmural myocardial blood flow in the unanesthetized dog.

R J Bache, R M Ball, F R Cobb, J C Rembert, J C Greenfield Jr
PMCID: PMC301876  PMID: 805796

Abstract

This study was designed to determin the effect of nitroglycerin upon transmural distribution of myocardial blood flow in the awake dog during normal conditions and in the presence of ischemia-induced coronary vasodilation. Studies were performed in chronically prepared dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was estimated by using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. During control conditions endocardial flow (0.86 plus or minus SEM 0.05 ml/min per g) slightly exceeded epicardial flow (0.72 plus or minus 0.03 ml/min per g, P smaller than 0.05), and this distribution of flow was not significantly altered by nitroglycerin. After a 5-s coronary artery occlusion, reactive hyperemia occurred with excess inflow of arterial blood effecting 360 plus or minus 15% repayment of the blood flow debt incurred during occlusion. When arterial inflow was limited to the preocclusion rate during coronary vasodilation after a 5-s total coronary artery occlusion, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium, and the delayed reactive hyperemia was markedly augmented (mean blood flow debt repayment =775plus or minus 105%, P smaller than 0.01). Tese data suggested that subendocardial underperfusion during the interval of coronary vasodilation in the presence of a flow-limiting proximal coronary artery stenosis caused continuing subendocardial ischemia which resulted in augmentation of the reactive hyperemic response. In this experimental model both the redistribution of myocardial blood flow which occurred during an interval of restricted arterial inflow after a 5-s coronary artery occlusion and augmentation of the subsequent reactive hyperemic response were returned toward normal by nitroglycerin. This effect of nitroglycerin may have resulted, at least in part, from its ability to vasodilate the penetrating arteries which deliver blood from the epicardial surface to the subendocardium.

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Selected References

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

  1. Alexander J. A., Sealy W. C., Greenfield J. C., Jr Improved technique for implanting electromagnetic flowmeter probes on the coronary artery. J Appl Physiol. 1969 Jul;27(1):139–140. doi: 10.1152/jappl.1969.27.1.139. [DOI] [PubMed] [Google Scholar]
  2. Bache R. J., Cobb F. R., Greenfield J. C., Jr Effects of increased myocardial oxygen consumption on coronary reactive hyperemia in the awake dog. Circ Res. 1973 Nov;33(5):588–596. doi: 10.1161/01.res.33.5.588. [DOI] [PubMed] [Google Scholar]
  3. Bache R. J., Cobb F. R., Greenfield J. C., Jr Myocardial blood flow distribution during ischemia-induced coronary vasodilation in the unanesthetized dog. J Clin Invest. 1974 Dec;54(6):1462–1472. doi: 10.1172/JCI107894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cobb F. R., Bache R. J., Greenfield J. C., Jr Regional myocardial blood flow in awake dogs. J Clin Invest. 1974 Jun;53(6):1618–1625. doi: 10.1172/JCI107712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen M. V., Kirk E. S. Differential response of large and small coronary arteries to nitroglycerin and angiotensin. Autoregulation and tachyphylaxis. Circ Res. 1973 Oct;33(4):445–453. doi: 10.1161/01.res.33.4.445. [DOI] [PubMed] [Google Scholar]
  6. Debley V. G. Miniature hydraulic occluder for zero blood flow determination. J Appl Physiol. 1971 Jul;31(1):138–139. doi: 10.1152/jappl.1971.31.1.138. [DOI] [PubMed] [Google Scholar]
  7. ECKSTEIN R. W. Effect of exercise and coronary artery narrowing on coronary collateral circulation. Circ Res. 1957 May;5(3):230–235. doi: 10.1161/01.res.5.3.230. [DOI] [PubMed] [Google Scholar]
  8. FAM W. M., MCGREGOR M. EFFECT OF CORONARY VASODILATOR DRUGS ON RETROGRADE FLOW IN AREAS OF CHRONIC MYOCARDIAL ISCHEMIA. Circ Res. 1964 Oct;15:355–364. doi: 10.1161/01.res.15.4.355. [DOI] [PubMed] [Google Scholar]
  9. Fam W. M., McGregor M. Effect of nitroglycerin and dipyridamole on regional coronary resistance. Circ Res. 1968 May;22(5):649–659. doi: 10.1161/01.res.22.5.649. [DOI] [PubMed] [Google Scholar]
  10. Griggs D. M., Jr, Nakamura Y. Effect of coronary constriction on myocardial distribution of iodoantipyrine-131-I. Am J Physiol. 1968 Nov;215(5):1082–1086. doi: 10.1152/ajplegacy.1968.215.5.1082. [DOI] [PubMed] [Google Scholar]
  11. KIRK E. S., HONIG C. R. AN EXPERIMENTAL AND THEORETICAL ANALYSIS OF MYOCARDIAL TISSUE PRESSURE. Am J Physiol. 1964 Aug;207:361–367. doi: 10.1152/ajplegacy.1964.207.2.361. [DOI] [PubMed] [Google Scholar]
  12. Koberstein R. C., Pittman D. E., Klocke F. J. Right atrial admixture in coronary venous blood. Am J Physiol. 1969 Mar;216(3):531–535. doi: 10.1152/ajplegacy.1969.216.3.531. [DOI] [PubMed] [Google Scholar]
  13. LITTER J., WILKINS R. W., WOOD J. E. Peripheral venoconstriction in human congestive heart failure. Circulation. 1956 Apr;13(4):524–527. doi: 10.1161/01.cir.13.4.524. [DOI] [PubMed] [Google Scholar]
  14. Lee S. J., Sung Y. K., Zaragoza A. J. Effects of nitroglycerin on left ventricular volumes and wall tension in patients with ischaemic heart disease. Br Heart J. 1970 Nov;32(6):790–794. doi: 10.1136/hrt.32.6.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moir T. W., DeBra D. W. Effect of left ventricular hypertension, ischemia and vasoactive drugs on the myocardial distribution of coronary flow. Circ Res. 1967 Jul;21(1):65–74. doi: 10.1161/01.res.21.1.65. [DOI] [PubMed] [Google Scholar]
  16. Moir T. W. Subendocardial distribution of coronary blood flow and the effect of antianginal drugs. Circ Res. 1972 Jun;30(6):621–627. doi: 10.1161/01.res.30.6.621. [DOI] [PubMed] [Google Scholar]
  17. OLSSON R. A., GREGG D. E. MYOCARDIAL REACTIVE HYPEREMIA IN THE UNANESTHETIZED DOG. Am J Physiol. 1965 Feb;208:224–230. doi: 10.1152/ajplegacy.1965.208.2.224. [DOI] [PubMed] [Google Scholar]
  18. Pauly T. J., Zarnstorff W. C., Bittar N. Myocardial metabolic activity as a determinant of reactive hyperaemia responses in the dog heart. Cardiovasc Res. 1973 Jan;7(1):90–94. doi: 10.1093/cvr/7.1.90. [DOI] [PubMed] [Google Scholar]
  19. Rolett E. L., Yurchak P. M., Hood W. B., Jr, Gorlin R. Pressure-volume correlates of left ventricular oxygen consumption in the hypervolemic dog. Circ Res. 1965 Dec;17(6):499–518. doi: 10.1161/01.res.17.6.499. [DOI] [PubMed] [Google Scholar]
  20. SALISBURY P. F., CROSS C. E., RIEBEN P. A. ACUTE ISCHEMIA OF INNER LAYERS OF VENTRICULAR WALL. Am Heart J. 1963 Nov;66:650–656. doi: 10.1016/0002-8703(63)90321-1. [DOI] [PubMed] [Google Scholar]
  21. WEST J. W., GUZMAN S. V. Coronary dilatation and constriction visualized by selective arteriography. Circ Res. 1959 Jul;7(4):527–536. doi: 10.1161/01.res.7.4.527. [DOI] [PubMed] [Google Scholar]
  22. Weiss H. R., Winbury M. M. Nitroglycerin and chromonar on small-vessel blood content of the ventricular walls. Am J Physiol. 1974 Apr;226(4):838–843. doi: 10.1152/ajplegacy.1974.226.4.838. [DOI] [PubMed] [Google Scholar]
  23. Williams J. F., Jr, Glick G., Braunwald E. Studies on cardiac dimensions in intact unanesthetized man. V. Effects of nitroglycerin. Circulation. 1965 Nov;32(5):767–771. doi: 10.1161/01.cir.32.5.767. [DOI] [PubMed] [Google Scholar]
  24. Winbury M. M., Howe B. B., Hefner M. A. Effect of nitrates and other coronary dilators on large and small coronary vessels: an hypothesis for the mechanism of action of nitrates. J Pharmacol Exp Ther. 1969 Jul;168(1):70–95. [PubMed] [Google Scholar]
  25. Winbury M. M., Howe B. B., Weiss J. R. Effect of nitroglycerin and dipyridamole on epicardial and endocardial oxygen tension--further evidence for redistribution of myocardial blood flow. J Pharmacol Exp Ther. 1971 Jan;176(1):184–199. [PubMed] [Google Scholar]
  26. Winbury M. M. Redistribution of left ventricular blood flow produced by nitroglycerin. An example of integration of the macro- and microcirculation. Circ Res. 1971 Jan;28(Suppl):140–147. [PubMed] [Google Scholar]

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