APROTININ IMPROVES MYOCARDIAL RECOVERY AFTER ISCHEMIA AND REPERFUSION- EFFECTS OF THE DRUG ON ISOLATED RAT HEARTS

The effects of aprotinin, a protease inhibitor, on the ischemic and no nischemic isolated rat heart was investigated with the use of the modi fied Langendorff model. During phase I of the study, hearts were perfu sed with either low-dose aprotinin (10(5) KIU/L), high-dose aprotinin (10(6) KIU/L), or normal saline solution added to modified Krebs-Hense leit solution. No statistically significant differences in contraction amplitude, contractility, coronary flow, and wet/dry heart weight rat io were observed among the three groups of hearts. In phase II, hearts were exposed to a 40-minute period of global ischemia at 31 degrees C . Ischemic arrest was induced. by warm cardioplegia. Before ischemia a nd during cardioplegia, hearts were perfused with either aprotinin 10( 6) KIU/L (n = 10) or normal saline solution (n = 10) for 30 minutes. O n reperfusion, recovery of hearts treated with aprotinin was significa ntly better than that of control hearts, as reflected by better contra ctility (analysis of variance, p = 0.011), higher coronary how (p < 0. 025), and lower creatine kinase levels (p < 0.05). No statistically si gnificant differences in contraction amplitude were observed between t he two groups. When the effect of ischemia within each group of hearts was analyzed, the preserving effect of aprotinin was even more pronou nced. In the control group, ischemia caused a decrease in contractilit y (p < 0.025) and a decrease in oxygen consumption (p = 0.006); by con trast, in the aprotinin group the preischemic values were maintained. Accordingly, we conclude that aprotinin at concentrations up to 10(6) KIU/L has no deleterious effect on normally perfused hearts and has a significant protective. effect on the ischemic heart when used in high doses in the preischemic period.