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Research Article Free access | 10.1172/JCI109284

Assessment of the Efficacy of Interventions to Limit Ischemic Injury by Direct Measurement of Intramural Carbon Dioxide Tension after Coronary Artery Occlusion in the Dog

L. David Hillis, Shukri F. Khuri, Eugene Braunwald, Robert A. Kloner, Donald Tow, Ernest Barsamian, and Peter R. Maroko

Department of Surgery, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Nuclear Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Harvard Medical School, Boston, Massachusetts 02115

Find articles by Hillis, L. in: PubMed | Google Scholar

Department of Surgery, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Nuclear Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Harvard Medical School, Boston, Massachusetts 02115

Find articles by Khuri, S. in: PubMed | Google Scholar

Department of Surgery, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Nuclear Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Harvard Medical School, Boston, Massachusetts 02115

Find articles by Braunwald, E. in: PubMed | Google Scholar

Department of Surgery, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Nuclear Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Harvard Medical School, Boston, Massachusetts 02115

Find articles by Kloner, R. in: PubMed | Google Scholar

Department of Surgery, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Nuclear Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Harvard Medical School, Boston, Massachusetts 02115

Find articles by Tow, D. in: PubMed | Google Scholar

Department of Surgery, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Nuclear Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Harvard Medical School, Boston, Massachusetts 02115

Find articles by Barsamian, E. in: PubMed | Google Scholar

Department of Surgery, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Nuclear Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Department of Medicine, West Roxbury Veterans Administration Hospital and Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Harvard Medical School, Boston, Massachusetts 02115

Find articles by Maroko, P. in: PubMed | Google Scholar

Published January 1, 1979 - More info

Published in Volume 63, Issue 1 on January 1, 1979
J Clin Invest. 1979;63(1):99–107. https://doi.org/10.1172/JCI109284.
© 1979 The American Society for Clinical Investigation
Published January 1, 1979 - Version history
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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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