DOES APROTININ INCREASE THE MYOCARDIAL DAMAGE IN THE SETTING OF ISCHEMIA AND PRECONDITIONING

Background. Aprotinin reduces postoperative bleeding in cardiac operat ions, but its association with perioperative myocardial infarction rem ains controversial. Ischemic preconditioning is a novel method of myoc ardial protection. Methods. To answer whether aprotinin increases post ischemic myocardial damage and also to characterize the effect of apro tinin on ischemic preconditioning, four groups of sheep were fully hep arinized to keep activated clotting time readings greater than 750 sec onds and subjected to 60 minutes of normothermic regional ischemia (di agonal artery occlusion) with 3 hours of reperfusion. Group I was the control with no treatment, group II received aprotinin (1 million KIU load followed by 250,000 KIU/h), group III underwent ischemic precondi tioning (three 5-minute intervals of ischemia and reperfusion) before prolonged 1-hour ischemia, and group IV underwent similar ischemic pre conditioning and received aprotinin. Area at risk was delineated by mo nastryl blue pigment, and infarction size by tetrazolium staining. Res ults. The ratios of weight of area at risk to left ventricular weight and left ventricular weight to body weight were constant between group s. Infarction size to area at risk ratio data demonstrated that aproti nin increases infarction size by 60% (infarction size to area at risk ratio from 52% +/- 10% to 84% +/- 10% for I versus II; p < 0.001). Apr otinin also attenuates the protective effect of ischemic preconditioni ng (infarction size to area at risk ratio from 25% +/- 4% to 41% +/- 6 %; p < 0.001). Conclusions. In the setting of ischemia, aprotinin incr eases myocardial damage. If, however, the heart is provided with prote ctive preconditioning, then the deleterious effect of aprotinin may be neutralized. From these data we suggest that aprotinin should nor be used routinely in cardiac operations unless extensive blood loss is an ticipated, such as in redo open heart operations.