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

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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.

Authors

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