Abstract
Although numerous interventions have been shown to exert a salutary effect on the ischemic myocardium, the severity of ischemia generally has been measured by indirect techniques. In the present investigation the effect of ischemia on intramural carbon dioxide tension (PmCO2) was measured directly in the open-chest, anesthetized dog with a mass spectrometer during repetitive 10-min coronary artery occlusions separated by 45-min periods of reflow; simultaneously, regional myocardial blood flow in the ischemic area was measured by 127Xenon washout. In all dogs the increase in PmCO2 from before to 10 min after the first occlusion (ΔPmCO2) exceeded that during subsequent occlusions. In those dogs not receiving an intervention (controls), ΔPmCO2 during the third occlusion was similar to that during the second occlusion. When propranolol, hyaluronidase, and nitroglycerin were administered to different groups of dogs before the third occlusion, each caused significantly smaller elevations in ΔPmCO2 than those occurring during the control second occlusion, and the combination of all three interventions induced the smallest increase in ΔPmCO2. Regional myocardial blood flow rose with hyaluronidase and was unchanged with propranolol, nitroglycerin, and the three drugs in combination. In contrast to these beneficial interventions, isoproterenol infused with the third occlusion caused a higher ΔPmCO2 than during the control second occlusion. It is concluded, first, that interventions that modify the severity of ischemia can be evaluated by measuring intramural carbon dioxide tension; second, that propranolol, hyaluronidase, and nitroglycerin reduce ischemic injury, whereas isoproterenol increases it; and third, that the combination of propranolol, hyaluronidase, and nitroglycerin exerts an additive beneficial effect on ischemia.
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Selected References
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- Askenazi J., Hillis L. D., Diaz P. E., Davis M. A., Braunwald E., Maroko P. R. The effects of hyaluronidase on coronary blood flow following coronary artery occlusion in the dog. Circ Res. 1977 Jun;40(6):566–571. doi: 10.1161/01.res.40.6.566. [DOI] [PubMed] [Google Scholar]
- Becker L. C., Ferreira R., Thomas M. Effect of propranolol and isoprenaline on regional left ventricular blood flow in experimental myocardial ischaemia. Cardiovasc Res. 1975 Mar;9(2):178–186. doi: 10.1093/cvr/9.2.178. [DOI] [PubMed] [Google Scholar]
- Bonte F. J., Parkey R. W., Stokely E. M., Lewis S. E., Horwitz L. D., Curry G. C. Radionuclide determination of myocardial blood flow. Semin Nucl Med. 1973 Apr;3(2):153–163. doi: 10.1016/s0001-2998(73)80012-1. [DOI] [PubMed] [Google Scholar]
- Borer J. S., Redwood D. R., Levitt B., Cagin N., Bianchi C., Vallin H., Epstein S. E. Reduction in myocardial ischemia with nitroglycerin or nitroglycerin plus phenylephrine administered during acute myocardial infarction. N Engl J Med. 1975 Nov 13;293(20):1008–1012. doi: 10.1056/NEJM197511132932002. [DOI] [PubMed] [Google Scholar]
- Brandi G., Fam W. M., McGregor M. Measurement of coronary flow in local areas of myocardium using xenon 133. J Appl Physiol. 1968 Mar;24(3):446–450. doi: 10.1152/jappl.1968.24.3.446. [DOI] [PubMed] [Google Scholar]
- Brantigan J. W., Gott V. L., Martz M. N. A Teflon membrane for measurement of blood and intramyocardial gas tensions by mass spectroscopy. J Appl Physiol. 1972 Feb;32(2):276–282. doi: 10.1152/jappl.1972.32.2.276. [DOI] [PubMed] [Google Scholar]
- Braunwald E., Maroko P. R. Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion. Am J Cardiol. 1976 Mar 31;37(4):550–556. doi: 10.1016/0002-9149(76)90395-7. [DOI] [PubMed] [Google Scholar]
- Clayman R., Johansen K. H., DeLaria G. A., Bernstein E. F. The hypertensive balloon. A beneficial synergism for the salvage of ischemic myocardium. J Thorac Cardiovasc Surg. 1974 Jul;68(1):80–89. [PubMed] [Google Scholar]
- Come P. C., Flaherty J. T., Baird M. G., Rouleau J. R., Weisfeldt M. L., Greene H. L., Becker L., Pitt B. Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction. N Engl J Med. 1975 Nov 13;293(20):1003–1007. doi: 10.1056/NEJM197511132932001. [DOI] [PubMed] [Google Scholar]
- Feola M., Limet R., Glick G. Synergistic effects of phenylephrine and counterpulsation in canine cardiogenic shock. Am J Physiol. 1973 May;224(5):1044–1053. doi: 10.1152/ajplegacy.1973.224.5.1044. [DOI] [PubMed] [Google Scholar]
- Flaherty J. T., Reid P. R., Kelly D. T., Taylor D. R., Weisfeldt M. L., Pitt B. Intravenous nitroglycerin in acute myocardial infarction. Circulation. 1975 Jan;51(1):132–139. doi: 10.1161/01.cir.51.1.132. [DOI] [PubMed] [Google Scholar]
- Ginks W., Ross J., Jr, Sybers H. D. Prevention of gross myocardial infarction in the canine heart. Arch Pathol. 1974 Jun;97(6):380–384. [PubMed] [Google Scholar]
- Gold H. K., Leinbach R. C., Maroko P. R. Propranolol-induced reduction of signs of ischemic injury during acute myocardial infarction. Am J Cardiol. 1976 Nov 23;38(6):689–695. doi: 10.1016/0002-9149(76)90344-1. [DOI] [PubMed] [Google Scholar]
- Heyndrickx G. R., Millard R. W., McRitchie R. J., Maroko P. R., Vatner S. F. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest. 1975 Oct;56(4):978–985. doi: 10.1172/JCI108178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hillis L. D., Askenazi J., Braunwald E., Radvany P., Muller J. E., Fishbein M. C., Maroko P. R. Use of changes in the epicardial QRS complex to assess interventions which modify the extent of myocardial necrosis following coronary artery occlusion. Circulation. 1976 Oct;54(4):591–598. doi: 10.1161/01.cir.54.4.591. [DOI] [PubMed] [Google Scholar]
- Hillis L. D., Braunwald E. Myocardial ischemia (second of three parts). N Engl J Med. 1977 May 5;296(18):1034–1041. doi: 10.1056/NEJM197705052961804. [DOI] [PubMed] [Google Scholar]
- Hillis L. D., Fishbein M. C., Braunwald E., Maroko P. R. The influence of the time interval between coronary artery occlusion and the administration of hyaluronidase on salvage of ischemic myocardium in dogs. Circ Res. 1977 Jul;41(1):26–31. doi: 10.1161/01.res.41.1.26. [DOI] [PubMed] [Google Scholar]
- 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]
- KIRK E. S., HONIG C. R. NONUNIFORM DISTRIBUTION OF BLOOD FLOW AND GRADIENTS OF OXYGEN TENSION WITHIN THE HEART. Am J Physiol. 1964 Sep;207:661–668. doi: 10.1152/ajplegacy.1964.207.3.661. [DOI] [PubMed] [Google Scholar]
- Khuri S. F., Flaherty J. T., O'Riordan J. B., Pitt B., Brawley R. K., Donahoo J. S., Gott V. L. Changes in intramyocardial ST segment voltage and gas tensions with regional myocardial ischemia in the dog. Circ Res. 1975 Oct;37(4):455–463. doi: 10.1161/01.res.37.4.455. [DOI] [PubMed] [Google Scholar]
- Khuri S. F., O'Riordan J., Flaherty J. T., Brawley R. K., Donahoo J. S., Gott V. L. Mass spectrometry for the measurement of intramyocardial gas tensions: methodology and application to the study of myocardial ischemia. Recent Adv Stud Cardiac Struct Metab. 1975;10:539–550. [PubMed] [Google Scholar]
- Klocke F. J. Coronary blood flow in man. Prog Cardiovasc Dis. 1976 Sep-Oct;19(2):117–166. doi: 10.1016/0033-0620(76)90020-7. [DOI] [PubMed] [Google Scholar]
- Kloner R. A., Fishbein M. C., Cotran R. S., Braunwald E., Maroko P. R. The effect of propranolol on microvascular injury in acute myocardial ischemia. Circulation. 1977 Jun;55(6):872–880. doi: 10.1161/01.cir.55.6.872. [DOI] [PubMed] [Google Scholar]
- Kloner R. A., Fishbein M. C., Maclean D., Braunwald E., Maroko P. R. Effect of hyaluronidase during the early phase of acute myocardial ischemia: an ultrastructural and morphometric analysis. Am J Cardiol. 1977 Jul;40(1):43–49. doi: 10.1016/0002-9149(77)90098-4. [DOI] [PubMed] [Google Scholar]
- Kloner R. A., Reimer K. A., Jennings R. B. Distribution of coronary collateral flow in acute myocardial ischaemic injury: effect of propranolol. Cardiovasc Res. 1976 Jan;10(1):81–90. doi: 10.1093/cvr/10.1.81. [DOI] [PubMed] [Google Scholar]
- Libby P., Maroko P. R., Covell J. W., Malloch C. I., Ross J., Jr, Braunwald E. Effect of practolol on the extent of myocardial ischaemic injury after experimental coronary occlusion and its effects of ventricular function in the normal and ischaemic heart. Cardiovasc Res. 1973 Mar;7(2):167–173. doi: 10.1093/cvr/7.2.167. [DOI] [PubMed] [Google Scholar]
- Liedtke A. J. Effects of coronary perfusion during myocardial hypoxia. Comparison of metabolic and hemodynamic events with global ischemia and hypoxemia. J Thorac Cardiovasc Surg. 1976 May;71(5):726–735. [PubMed] [Google Scholar]
- Maclean D., Fishbein M. C., Maroko P. R., Braunwald E. Hyaluronidase-induced reductions in myocardial infarct size. Science. 1976 Oct 8;194(4261):199–200. doi: 10.1126/science.959848. [DOI] [PubMed] [Google Scholar]
- Maroko P. R., Davidson D. M., Libby P., Hagan A. D., Braunwald E. Effects of hyaluronidase administration on myocardial ischemic injury in acute infarction. A preliminary study in 24 patients. Ann Intern Med. 1975 Apr;82(4):516–520. doi: 10.7326/0003-4819-82-4-516. [DOI] [PubMed] [Google Scholar]
- Maroko P. R., Hillis L. D., Muller J. E., Tavazzi L., Heyndrickx G. R., Ray M., Chiariello M., Distante A., Askenazi J., Salerno J. Favorable effects of hyaluronidase on electrocardiographic evidence of necrosis in patients with acute myocardial infarction. N Engl J Med. 1977 Apr 21;296(16):898–903. doi: 10.1056/NEJM197704212961603. [DOI] [PubMed] [Google Scholar]
- Maroko P. R., Kjekshus J. K., Sobel B. E., Watanabe T., Covell J. W., Ross J., Jr, Braunwald E. Factors influencing infarct size following experimental coronary artery occlusions. Circulation. 1971 Jan;43(1):67–82. doi: 10.1161/01.cir.43.1.67. [DOI] [PubMed] [Google Scholar]
- Maroko P. R., Libby P., Bloor C. M., Sobel B. E., Braunwald E. Reduction by hyaluronidase of myocardial necrosis following coronary artery occlusion. Circulation. 1972 Sep;46(3):430–437. doi: 10.1161/01.cir.46.3.430. [DOI] [PubMed] [Google Scholar]
- Maroko P. R., Libby P., Covell J. W., Sobel B. E., Ross J., Jr, Braunwald E. Precordial S-T segment elevation mapping: an atraumatic method for assessing alterations in the extent of myocardial ischemic injury. The effects of pharmacologic and hemodynamic interventions. Am J Cardiol. 1972 Feb;29(2):223–230. doi: 10.1016/0002-9149(72)90633-9. [DOI] [PubMed] [Google Scholar]
- Mueller H. S., Ayres S. M., Religa A., Evans R. G. Propranolol in the treatment of acute myocardial infarction. Effect on myocardial oxygenation and hemodynamics. Circulation. 1974 Jun;49(6):1078–1087. doi: 10.1161/01.cir.49.6.1078. [DOI] [PubMed] [Google Scholar]
- Muller J. E., Maroko P. R., Braunwald E. Evaluation of precordial electrocardiographic mapping as a means of assessing changes in myocardial ischemic injury. Circulation. 1975 Jul;52(1):16–27. doi: 10.1161/01.cir.52.1.16. [DOI] [PubMed] [Google Scholar]
- Myers R. W., Scherer J. L., Goldstein R. A., Goldstein R. E., Kent K. M., Epstein S. E. Effects of nitroglycerin and nitroglycerin-methoxamine during acute myocardial ischemia in dogs with pre-existing multivessel coronary occlusive disease. Circulation. 1975 Apr;51(4):632–640. doi: 10.1161/01.cir.51.4.632. [DOI] [PubMed] [Google Scholar]
- Parmley W. W., Chatterjee K., Charuzi Y., Swan H. J. Hemodynamic effects of noninvasive systolic unloading (nitroprusside) and diastolic augmentation (external counterpulsation) in patients with acute myocardial infarction. Am J Cardiol. 1974 Jun;33(7):819–825. doi: 10.1016/0002-9149(74)90627-4. [DOI] [PubMed] [Google Scholar]
- Pitt B., Craven P. Effect of propranolol on regional myocardial blood flow in acute ischaemia. Cardiovasc Res. 1970 Apr;4(2):176–179. doi: 10.1093/cvr/4.2.176. [DOI] [PubMed] [Google Scholar]
- Rasmussen M. M., Reimer K. A., Kloner R. A., Jennings R. B. Infarct size reduction by propranolol before and after coronary ligation in dogs. Circulation. 1977 Nov;56(5):794–798. doi: 10.1161/01.cir.56.5.794. [DOI] [PubMed] [Google Scholar]
- Reimer K. A., Rasmussen M. M., Jennings R. B. On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs. Am J Cardiol. 1976 Mar 31;37(4):520–527. doi: 10.1016/0002-9149(76)90391-x. [DOI] [PubMed] [Google Scholar]
- Reimer K. A., Rasmussen M. M., Jennings R. B. Reduction by propranolol of myocardial necrosis following temporary coronary artery occlusion in dogs. Circ Res. 1973 Sep;33(3):353–363. doi: 10.1161/01.res.33.3.353. [DOI] [PubMed] [Google Scholar]
- Smith E. R., Redwood D. R., McCarron W. E., Epstein S. E. Coronary artery occlusion in the conscious dog. Effects of alterations in arterial pressure produced by nitroglycerin, hemorrhage, and alpha-adrenergic agonists on the degree of myocardial ischemia. Circulation. 1973 Jan;47(1):51–57. doi: 10.1161/01.cir.47.1.51. [DOI] [PubMed] [Google Scholar]
- Sullivan J. M., Taylor W. J., Elliott W. C., Gorlin R. Regional myocardial blood flow. J Clin Invest. 1967 Sep;46(9):1402–1412. doi: 10.1172/JCI105632. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vatner S. F., Baig H., Manders W. T., Ochs H., Pagani M. Effects of propranolol on regional myocardial function, electrograms, and blood flow in conscious dogs with myocardial ischemia. J Clin Invest. 1977 Aug;60(2):353–360. doi: 10.1172/JCI108783. [DOI] [PMC free article] [PubMed] [Google Scholar]