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. 1973 Nov;52(11):2836–2847. doi: 10.1172/JCI107479

The Effects of Nitroglycerin on Coronary Collaterals and Myocardial Contractility

Michael V Cohen 1, James M Downey 1, Edmund H Sonnenblick 1, Edward S Kirk 1
PMCID: PMC302551  PMID: 4201267

Abstract

Nitroglycerin (TNG) causes a prolonged dilatation of coronary collaterals. To demonstrate a functional significance of this dilatation we measured the effect of TNG on myocardial contractile force in dogs 2½-4 wk after the left anterior descending coronary artery (LAD) had been embolized in closed-chest animals. Development of collaterals was documented by angiography. Via a left thoracotomy the main left coronary artery (LCA) and LAD distal to the embolized plug were cannulated. Coronary flow and perfusion pressure were recorded. Contractile force was measured with gauges sutured to epicardial areas supplied by the left circumflex coronary artery (LCf) and occluded LAD. Coronary perfusion pressure in the LCA was gradually decreased until the contractile force recorded by the LAD gauge diminished while the LCf gauge was unaffected. Under these conditions, with coronary perfusion pressure held constant with the aid of a Starling resistance, TNG (18 μg) injected into the LCA increased peripheral LAD pressure by 3-12 mm Hg and contractile force in the LAD region by 36% (range 20-90%), returning it to near-normal levels, while having minimal effect in the LCf area. These changes persisted for 5 min. When LCf and LAD areas were both ischemic, intracoronary TNG had minimal effect on peripheral LAD pressure and contractile force. Thus, TNG causes prolonged dilatation of coronary collaterals and presumed increased collateral flow with subsequent enhancement of myocardial contractile force in ischemic areas. This effect is seen only when ischemia is limited to an area supplied by the collaterals. When the whole heart is ischemic, collaterals are unresponsive to TNG, suggesting that these collaterals dilate fully when the regions from which they originate become ischemic.

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Selected References

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

  1. BRACHFELD N., BOZER J., GORIN R. Action of nitroglycerin on the coronary circulation in normal and in mild cardiac subjects. Circulation. 1959 May;19(5):697–704. doi: 10.1161/01.cir.19.5.697. [DOI] [PubMed] [Google Scholar]
  2. Becker L. C., Fortuin N. J., Pitt B. Effect of ischemia and antianginal drugs on the distribution of radioactive microspheres in the canine left ventricle. Circ Res. 1971 Feb;28(2):263–269. doi: 10.1161/01.res.28.2.263. [DOI] [PubMed] [Google Scholar]
  3. Becker L. C., Pitt B. Collateral blood flow in conscious dogs with chronic coronary artery occlusion. Am J Physiol. 1971 Nov;221(5):1507–1510. doi: 10.1152/ajplegacy.1971.221.5.1507. [DOI] [PubMed] [Google Scholar]
  4. Berne R. M., Rubio R., Dobson J. G., Jr, Curnish R. R. Adenosine and adenine nucleotides as possible mediators of cardiac and skeletal muscle blood flow regulation. Circ Res. 1971 Jan;28(Suppl):115+–115+. [PubMed] [Google Scholar]
  5. Bernstein L., Friesinger G. C., Lichtlen P. R., Ross R. S. The effect of nitroglycerin on the systemic and coronary circulation in man and dogs: myocardial blood flow measured with xenon. Circulation. 1966 Jan;33(1):107–116. doi: 10.1161/01.cir.33.1.107. [DOI] [PubMed] [Google Scholar]
  6. Blum R. L., Alpern H., Jaffe H., Lang T. W., Corday E. Determination of interarterial coronary anastomosis by radioactive spherules. Effect of coronary occlusion and hypoxemia. Am Heart J. 1970 Feb;79(2):244–249. doi: 10.1016/0002-8703(70)90314-5. [DOI] [PubMed] [Google Scholar]
  7. Carson R. P., Wilson W. S., Nemiroff M. J., Weber W. J. The effects of sublingual nitroglycerin on myocardial blood flow in patients with coronary artery disease or myocardial hypertrophy. Am Heart J. 1969 May;77(5):579–584. doi: 10.1016/0002-8703(69)90541-9. [DOI] [PubMed] [Google Scholar]
  8. Cibulski A. A., Lehan P. H., Timmis H. H. Retrograde flow technique vs. krypton-85 clearance technique for estimation of myocardial collaterals. Am J Physiol. 1972 Nov;223(5):1081–1087. doi: 10.1152/ajplegacy.1972.223.5.1081. [DOI] [PubMed] [Google Scholar]
  9. Cowan C., Duran P. V., Corsini G., Goldschlager N., Bing R. J. The effects of nitroglycerin on myocardial blood flow in man, measured by coincidence counting and bolus injections of 84-rubidium. Am J Cardiol. 1969 Aug;24(2):154–160. doi: 10.1016/0002-9149(69)90397-x. [DOI] [PubMed] [Google Scholar]
  10. Elliot E. C., Bloor C. M., Jones E. L., Mitchell W. J., Gregg D. E. Effect of controlled coronary occlusion on collateral circulation in conscious dogs. Am J Physiol. 1971 Apr;220(4):857–861. doi: 10.1152/ajplegacy.1971.220.4.857. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Forman R., Kirk E. S., Downey J. M., Sonnenblick E. H. Nitroglycerin and heterogeneity of myocardial blood flow. Reduced subendocardial blood flow and ventricular contractile force. J Clin Invest. 1973 Apr;52(4):905–911. doi: 10.1172/JCI107255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ganz W., Marcus H. S. Failure of intracoronary nitroglycerin to alleviate pacing-induced angina. Circulation. 1972 Nov;46(5):880–889. doi: 10.1161/01.cir.46.5.880. [DOI] [PubMed] [Google Scholar]
  15. Gensini G. G., Kelly A. E., Da Costa B. C., Huntington P. P. Quantitative angiography: the measurement of coronary vasomobility in the intact animal and man. Chest. 1971 Dec;60(6):522–530. doi: 10.1378/chest.60.6.522. [DOI] [PubMed] [Google Scholar]
  16. Grayson J., Irvine M. Myocardial infarction in the monkey: studies on the collateral circulation after acute coronary occlusion. Cardiovasc Res. 1968 Apr;2(2):170–178. doi: 10.1093/cvr/2.2.170. [DOI] [PubMed] [Google Scholar]
  17. Gundel W. D., Brown B. G., Gott V. L. Coronary collateral flow studies during variable aortic root pressure waveforms. J Appl Physiol. 1970 Nov;29(5):579–586. doi: 10.1152/jappl.1970.29.5.579. [DOI] [PubMed] [Google Scholar]
  18. Haft J. I., Damato A. N. Measurement of collateral blood flow after myocardial infarction in the closed-chest dog. Am Heart J. 1969 May;77(5):641–648. doi: 10.1016/0002-8703(69)90549-3. [DOI] [PubMed] [Google Scholar]
  19. Hilger H. H. Experimentelle Prüfung der Wirkung von Corondardilatatoren am Menschen. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1969;263(1):168–184. [PubMed] [Google Scholar]
  20. Horwitz L. D., Gorlin R., Taylor W. J., Kemp H. G. Effects of nitroglycerin on regional myocardial blood flow in coronary artery disease. J Clin Invest. 1971 Aug;50(8):1578–1584. doi: 10.1172/JCI106645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. KATTUS A. A., GREGG D. E. Some determinants of coronary collateral blood flow in the open-chest dog. Circ Res. 1959 Jul;7(4):628–642. doi: 10.1161/01.res.7.4.628. [DOI] [PubMed] [Google Scholar]
  22. Linder E., Seeman T. Effects of persantin and nitroglycerin on myocardial blood flow during temporary coronary occlusions in dogs. Angiologica. 1967;4(5):225–255. doi: 10.1159/000157708. [DOI] [PubMed] [Google Scholar]
  23. MARCHETTI G. V., MERLO L., ANTOGNETTI R. M. THE EFFECTS OF NITROGLYCERIN ON THE CORONARY BLOOD FLOW AND OXYGEN CONSUMPTION OF THE MYOCARDIUM IN ANESTHETIZED DOGS. Am J Cardiol. 1964 Jan;13:51–57. doi: 10.1016/0002-9149(64)90222-x. [DOI] [PubMed] [Google Scholar]
  24. MOSHER P., ROSS J., Jr, MCFATE P. A., SHAW R. F. CONTROL OF CORONARY BLOOD FLOW BY AN AUTOREGULATORY MECHANISM. Circ Res. 1964 Mar;14:250–259. doi: 10.1161/01.res.14.3.250. [DOI] [PubMed] [Google Scholar]
  25. Mason D. T., Braunwald E. The effects of nitroglycerin and amyl nitrite on arteriolar and venous tone in the human forearm. Circulation. 1965 Nov;32(5):755–766. doi: 10.1161/01.cir.32.5.755. [DOI] [PubMed] [Google Scholar]
  26. Mason D. T., Zelis R., Amsterdam E. A. Actions of the nitrites on the peripheral circulation and myocardial oxygen consumption: significance in the relief of angina pectoris. Chest. 1971 Mar;59(3):296–305. doi: 10.1378/chest.59.3.296. [DOI] [PubMed] [Google Scholar]
  27. McGregor M., Fam W. M. Regulation of coronary blood flow. Bull N Y Acad Med. 1966 Nov;42(11):940–950. [PMC free article] [PubMed] [Google Scholar]
  28. Menick F. J., White F. C., Bloor C. M. Coronary collateral circulation: determination of an anatomical anastomotic index of functional collateral flow capacity. Am Heart J. 1971 Oct;82(4):503–510. doi: 10.1016/0002-8703(71)90235-3. [DOI] [PubMed] [Google Scholar]
  29. Nishimura A., Giron F., Birtwell W. C., Soroff H. S. Evaluation of collateral blood supply by direct measurement of the performance of ischemic myocardial muscle. Trans Am Soc Artif Intern Organs. 1970;16:450–454. [PubMed] [Google Scholar]
  30. Pasyk S., Bloor C. M., Khouri E. M., Gregg D. E. Systemic and coronary effects of coronary artery occlusion in the unanesthetized dog. Am J Physiol. 1971 Mar;220(3):646–654. doi: 10.1152/ajplegacy.1971.220.3.646. [DOI] [PubMed] [Google Scholar]
  31. Redding V. J., Rees J. R. Early changes in collateral flow following coronary artery ligation: the role of the sympathetic nervous system. Cardiovasc Res. 1968 Jul;2(3):219–225. doi: 10.1093/cvr/2.3.219. [DOI] [PubMed] [Google Scholar]
  32. Rees J. R., Redding V. J., Ashfield R., Gibson D., Gavey C. J. Myocardial blood flow measurement with 133-Xenon effect of glyceryl trinitrate in dogs. Br Heart J. 1966 May;28(3):374–381. doi: 10.1136/hrt.28.3.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rees J. R., Redding V. J. Increase in myocardial collateral capacity following drug-induced coronary vasodilatation. A preliminary report. Am Heart J. 1969 Aug;78(2):224–228. doi: 10.1016/0002-8703(69)90012-x. [DOI] [PubMed] [Google Scholar]
  34. Schnaar R. L., Sparks H. V. Response of large and small coronary arteries to nitroglycerin, NaNO 2 , and adenosine. Am J Physiol. 1972 Jul;223(1):223–228. doi: 10.1152/ajplegacy.1972.223.1.223. [DOI] [PubMed] [Google Scholar]
  35. Vyden J. K., Carvalho M., Boszormenyi E., Lang T. W., Bernstein H., Corday E. Effect of glyceryl trinitrate (nitroglycerin) on the systemic and coronary circulation of the dog. Am J Cardiol. 1970 Jan;25(1):53–58. doi: 10.1016/0002-9149(70)90814-3. [DOI] [PubMed] [Google Scholar]
  36. WINBURY M. M. EXPERIMENTAL APPROACHES TO THE DEVELOPMENT OF ANTIANGINAL DRUGS. Adv Pharmacol. 1964;3:1–82. doi: 10.1016/s1054-3589(08)61110-2. [DOI] [PubMed] [Google Scholar]
  37. 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]

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