Effect of the kallikrein inhibitor aprotinin on myocardial ischemic injury after coronary occlusion in the dog

Abstract

The effect of administration of aprotinin (a kallikrein inhibitor) on the extent and severity of acute myocardial ischemic injury, subsequent necrosis and collateral blood flow was studied in 55 dogs after acute coronary occlusion. Two 20 minute occlusions of the left anterior coronary artery were performed in eight dogs and epicardial electrograms were recorded from 10 to 14 sites. The sum of S-T segment elevations (σST) 15 minutes after the occlusion without drug administration was 38.7 ± 7.0 mv (mean ± standard error of the mean). Before the second occlusion aprotinin was administered and σST decreased to 22.6 ± 5.6 mv ( P < 0.01). Similarly, the number of sites exhibiting S-T segment elevations of more than 2 mv (NST) decreased from 6.4 ± 0.8 after the first occlusion to 4.2 ± 1.2 ( P < 0.01) after the occlusion following aprotinin administration. The effect of aprotinin on myocardial necrosis administered 30 minutes after coronary occlusion was established by means of the relation between epicardial S-T segment elevation 15 minutes after coronary occlusion and myocardial creatine kinase (CK) activity and histologic appearance at the same sites 24 hours later. In the control group the relation was: log CK = −0.059S-T + 1.53 (no. = 92 specimens, r = 0.74); in the treated group it was: log CK = —0.036S-T + 1.54 (no. = 60 specimens, r = 0.79). These slopes differed ( P < 0.001), indicating that aprotinin prevented myocardial CK depletion. In the control group all sites exhibiting S-T elevations of more than 2 mv 15 minutes after occlusion showed early signs of myocardial infarction 24 hours later when examined by light microscopy. In contrast, in dogs that received aprotinin, only 66 percent of sites with abnormally elevated S-T segments showed abnormal histologic features, indicating that administration of the drug led to preservation of structural integrity in many sites. Similarly, significantly deeper Q waves evolved in the control than in the treated group: ΔQ (6 hours) = 0.82 S-T (15 min) + 0.86 (no. = 9 dogs, r = 0.76) and in the treated group: ΔQ (6 hours) = 0.46S-T (15 min) + 0.72 (no. = 10 dogs, r = 0.64) ( P < 0.02). Regional myocardial blood flow decreased from 15 minutes to 6 hours after occlusion in both the control and treated groups. However, the decrease was less in the treated than in the control group (37 versus 16 percent and the distribution of flow endocardialepicardial ratio was significantly better with aprotinin. Thus, it is concluded that aprotinin diminishes myocardial damage after acute coronary occlusion.