Reduction in Severity and Extent of Myocardial Infarction When Nitroglycerin and Methoxamine are Administered during Coronary Occlusion

Abstract

The effects of treatment with nitroglycerin (TNG) and methoxamine on the degree of ischemic injury occurring during 5 hours of coronary occlusion were studied in 31 closed-chest sedated dogs. Acute coronary occlusion was produced by inflating a cuff previously implanted around the left anterior descending coronary artery. After 10 min of ischemia (assessed by intramyocardial electrodes), dogs were randomized into control and treated groups. Treated dogs received i.v. TNG during the remainder of the 5 hour occlusion. Arterial pressure was maintained at preinfusion levels with i.v. methoxamine. Six of 16 control dogs died; three of 15 treated dogs died. After 24 hours severity of infarct was assessed in survivors by gross inspection, and more quantitatively, by measurement of creatine phosphokinase (CPK) content of myocardium adjacent to each electrode. Transmural infarction was observed in all of the ten surviving control animals but in only two of the 12 treated animals. In control dogs, CPK was inversely related to ST segment elevation observed after 10 min of occlusion: the greater the ST elevation, the lower the myocardial CPK level. This relation was modified in the treated group: at comparable initial levels of ischemia (as judged by ST segment elevation prior to treatment), treated dogs had significantly less CPK depression than control dogs ( P < 0.025). Moreover, in controls, a significant reduction in CPK occurred at 48 of 57 electrode sites where ST elevation was observed after 10 min of occlusion. Only 19 of 69 such sites showed significant CPK reduction in the treated dogs ( P < 0.001). Thus, administration of TNG, with support of arterial pressure by methoxamine, markedly reduces the severity and extent of infarction occurring after 5 hours of coronary occlusion in the dog.