Abstract
The effects of intravenous and sublingual glyceryl trinitrate (nitroglycerin), 40 μg/kg, were studied on coronary blood flow and resistance, left ventricular (LV) pressures (P) and diameters (D), rate of change of pressure (dP/dt), (dP/dt)/P, and on the velocity (V) of myocardial fiber shortening in conscious dogs. Nitroglycerin i.v. caused substantial coronary vasodilatation prior to any changes in systemic hemodynamics. Mean coronary flow increased by a maximum of 47 ml/min and coronary sinus Po2 rose from 16 to 26 mm Hg while pressure and diameter began to fall, and heart rate began to rise. After the maximal fall in mean arterial pressure (—26 mm Hg), a secondary peak in coronary flow occurred which was associated with increases in heart rate (100 beats/min), (dP/dt)/P (22%), and isolength V (12%). Beta blockade prevented the reflex increases in contractility but only a part of the reflex tachycardia; the remainder was prevented by cholinergic blockade. Maintaining heart rate constant minimized the decreases in LV D and increases in contractility. When the reflex inotropic and chronotropic effects were prevented by a combination of atrial pacing and beta blockade the early coronary vasodilatation was unaltered, but the later coronary vasodilatation was minimized.
Thus i.v. nitroglycerin in the conscious dog exerts a potent direct coronary vasodilating action and also a secondary coronary vasodilation caused by reflex increases in contractility and heart rate. The decreases in diameter are largely the result of tachycardia. Sublingual nitroglycerin produced directionally similar, but quantitatively lesser effects on coronary flow and resistance, LV D, LV P, and contractility.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aviado D. M., Folle L. E., Bellet S. Cardiopulmonary effects of glyceryl trinitrate and isosorbide dinitrate. Cardiologia. 1968;52(5):287–303. doi: 10.1159/000166129. [DOI] [PubMed] [Google Scholar]
- BERGAMASCHI M., GLAESSER A. H. EFFECT OF THE ENDECAPEPTIDE ELEDOISIN ON THE CORONARY BLOOD FLOW: COMPARISON WITH NITROGLYCERIN, BRADYKININ AND EPINEPHRINE IN THE DOG. Circ Res. 1963 Oct;13:329–335. doi: 10.1161/01.res.13.4.329. [DOI] [PubMed] [Google Scholar]
- BERNE R. M. REGULATION OF CORONARY BLOOD FLOW. Physiol Rev. 1964 Jan;44:1–29. doi: 10.1152/physrev.1964.44.1.1. [DOI] [PubMed] [Google Scholar]
- BING R. J., BENNISH A., BLUEMCHEN G., COHEN A., GALLAGHER J. P., ZALESKI E. J. THE DETERMINATION OF CORONARY FLOW EQUIVALENT WITH COINCIDENCE COUNTING TECHNIC. Circulation. 1964 Jun;29:833–846. doi: 10.1161/01.cir.29.6.833. [DOI] [PubMed] [Google Scholar]
- 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]
- BRANDT J. L., CACCESE A., DOCK W. Slit-kymographic evidence that nitroglycerine decreases heart volume and stroke volume while increasing the amplitude of ballistocardiographic waves. Am J Med. 1952 Jun;12(6):650–658. doi: 10.1016/0002-9343(52)90340-9. [DOI] [PubMed] [Google Scholar]
- 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]
- Braunwald E. Control of myocardial oxygen consumption: physiologic and clinical considerations. Am J Cardiol. 1971 Apr;27(4):416–432. doi: 10.1016/0002-9149(71)90439-5. [DOI] [PubMed] [Google Scholar]
- Cohen A., Gallagher J. P., Luebs E. D., Varga Z., Yamanaka J., Zaleski E. J., Bluemchen G., Bing R. J. The quantitative determination of coronary flow with a positron (rubidium-84). Circulation. 1965 Oct;32(4):636–649. doi: 10.1161/01.cir.32.4.636. [DOI] [PubMed] [Google Scholar]
- DARBY T. D., ALDINGER E. E. Further studies of the effects on myocardial energy utilization elicited by nitroglycerin. Circ Res. 1960 Jan;8:100–108. doi: 10.1161/01.res.8.1.100. [DOI] [PubMed] [Google Scholar]
- DARBY T. D., SPROUSE J. H., WALTON R. P. Evaluation of sympathetic reflex effects on the inotropic action of nitroglycerin, quinidine, papaverine, aminophylline and isoproterenol. J Pharmacol Exp Ther. 1958 Mar;122(3):386–395. [PubMed] [Google Scholar]
- ECKSTEIN R. W., NEWBERRY W. B., McEACHEN J. A., SMITH G. Studies of the antiadrenergic effects of nitroglycerin on the dog heart. Circulation. 1951 Oct;4(4):534–540. doi: 10.1161/01.cir.4.4.534. [DOI] [PubMed] [Google Scholar]
- ELLIS R. M., FRANKLIN D. L., RUSHMER R. F. Left ventricular dimensions recorded by sonocardiometry. Circ Res. 1956 Nov;4(6):684–688. doi: 10.1161/01.res.4.6.684. [DOI] [PubMed] [Google Scholar]
- 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]
- Franklin D. E., Watson N. W., Pierson K. E., Van Citters R. L. Technique for radio telemetry of blood-flow velocity from unrestrained animals. Am J Med Electron. 1966;5(1):24–28. [PubMed] [Google Scholar]
- GLICK G., SONNENBLICK E. H., BRAUNWALD E. MYOCARDIAL FORCE-VELOCITY RELATIONS STUDIED IN INTACT UNANESTHETIZED MAN. J Clin Invest. 1965 Jun;44:978–988. doi: 10.1172/JCI105215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GREGG D. E., KHOURI E. M., RAYFORD C. R. SYSTEMIC AND CORONARY ENERGETICS IN THE RESTING UNANESTHETIZED DOG. Circ Res. 1965 Feb;16:102–113. doi: 10.1161/01.res.16.2.102. [DOI] [PubMed] [Google Scholar]
- Gillis R. A., Melville K. I. Coronary flow changes and cardiac adrenergic blockade during nitroglycerin infusions. Eur J Pharmacol. 1970;13(1):15–22. doi: 10.1016/0014-2999(70)90175-5. [DOI] [PubMed] [Google Scholar]
- Gillis R. A., Melville K. I. Effects of sublingually and intravenously administered nitroglycerin on the cardiovascular system of the dog. Am J Cardiol. 1971 Jul;28(1):38–42. doi: 10.1016/0002-9149(71)90032-4. [DOI] [PubMed] [Google Scholar]
- HOLLANDER W., MADOFF I. M., CHOBANIAN A. V. Local myocardial blood flow as indicated by the disappearance of Nal-131 from the heart muscle: studies at rest, during exercise, and following nitrite administration. J Pharmacol Exp Ther. 1963 Jan;139:53–59. [PubMed] [Google Scholar]
- Hakumäki M. O. Function of the left atrial receptors. Acta Physiol Scand Suppl. 1970;344:1–54. [PubMed] [Google Scholar]
- Korner P. I. Integrative neural cardiovascular control. Physiol Rev. 1971 Apr;51(2):312–367. doi: 10.1152/physrev.1971.51.2.312. [DOI] [PubMed] [Google Scholar]
- Luebs E. D., Cohen A., Zaleski E. J., Bing R. J. Effect of nitroglycerin, intensain, isoptin and papaverine on coronary blood flow in man. Measured by the coincidence counting technic and rubidium. Am J Cardiol. 1966 Apr;17(4):535–541. doi: 10.1016/0002-9149(66)90245-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Malindzak G. S., Jr, Green H. D., Stagg P. L. Effects of nitroglycerin on flow after partial constriction of the coronary artery. J Appl Physiol. 1970 Jul;29(1):17–22. doi: 10.1152/jappl.1970.29.1.17. [DOI] [PubMed] [Google Scholar]
- Mason D. T., Braunwald E., Covell J. W., Sonnenblick E. H., Ross J., Jr Assessment of cardiac contractility. The relation between the rate of pressure rise and ventricular pressure during isovolumic systole. Circulation. 1971 Jul;44(1):47–58. doi: 10.1161/01.cir.44.1.47. [DOI] [PubMed] [Google Scholar]
- Mathes P., Rival J. Effect of nitroglycerin on total and regional coronary blood flow in the normal and ischaemic canine myocardium. Cardiovasc Res. 1971 Jan;5(1):54–61. doi: 10.1093/cvr/5.1.54. [DOI] [PubMed] [Google Scholar]
- O'Rourke R. A., Bishop V. S., Kot P. A., Fernandez J. P. Hemodynamic effects of nitroglycerin and amyl nitrite in the conscious dog. J Pharmacol Exp Ther. 1971 May;177(2):426–432. [PubMed] [Google Scholar]
- Parker J. O., West R. O., Di Giorgi S. The effect of nitroglycerin on coronary blood flow and the hemodynamic response to exercise in coronary artery disease. Am J Cardiol. 1971 Jan;27(1):59–65. doi: 10.1016/0002-9149(71)90083-x. [DOI] [PubMed] [Google Scholar]
- ROWE G. G., CHELIUS C. J., AFONSO S., GURTNER H. P., CRUMPTON C. W. Systemic and coronary hemodynamic effects of erythrol tetranitrate. J Clin Invest. 1961 Jul;40:1217–1222. doi: 10.1172/JCI104352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross G., Jorgensen C. Effects of iproveratril and nitroglycerin in the heart and coronary circulation of dogs. Am Heart J. 1968 Jul;76(1):74–78. doi: 10.1016/0002-8703(68)90297-4. [DOI] [PubMed] [Google Scholar]
- Stegall H. F., Kardon M. B., Stone H. L., Bishop V. S. A portable, simple sonomicrometer. J Appl Physiol. 1967 Aug;23(2):289–293. doi: 10.1152/jappl.1967.23.2.289. [DOI] [PubMed] [Google Scholar]
- Van Citters R. L., Franklin D. L. Telemetry of blood pressure in free-ranging animals via an intravascular gauge. J Appl Physiol. 1966 Sep;21(5):1633–1636. doi: 10.1152/jappl.1966.21.5.1633. [DOI] [PubMed] [Google Scholar]
- Vatner S. F., Franklin D., Braunwald E. Effects of anesthesia and sleep on circulatory response to carotid sinus nerve stimulation. Am J Physiol. 1971 May;220(5):1249–1255. doi: 10.1152/ajplegacy.1971.220.5.1249. [DOI] [PubMed] [Google Scholar]
- Vatner S. F., Franklin D., VanCitters R. L. Simultaneous comparison and calibration of the Doppler and electromagnetic flowmeters. J Appl Physiol. 1970 Dec;29(6):907–910. doi: 10.1152/jappl.1970.29.6.907. [DOI] [PubMed] [Google Scholar]
- Vatner S. F., Higgins C. B., Franklin D., Braunwald E. Effects of a digitalis glycoside on coronary and systemic dynamics in conscious dogs. Circ Res. 1971 Apr;28(4):470–479. doi: 10.1161/01.res.28.4.470. [DOI] [PubMed] [Google Scholar]
- Vatner S. F., Higgins C. B., Franklin D., Braunwald E. Extent of carotid sinus regulation of the myocardial contractile state in conscious dogs. J Clin Invest. 1972 Apr;51(4):995–1008. doi: 10.1172/JCI106893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vatner S. F., Higgins C. B., Patrick T., Franklin D., Braunwald E. Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside. J Clin Invest. 1971 Dec;50(12):2585–2595. doi: 10.1172/JCI106759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Wolk M. J., Keefe J. F., Bing O. H., Finkelstein L. J., Levine H. J. Estimation of Vmax in auxotonic systoles from the rate of relative increase of isovolumic pressure: (dP-dt)kP. J Clin Invest. 1971 Jun;50(6):1276–1285. doi: 10.1172/JCI106606. [DOI] [PMC free article] [PubMed] [Google Scholar]