Does aprotinin increase the myocardial damage in the setting of ischemia and preconditioning?

Background. Aprotinin reduces postoperative bleeding in cardiac operations, but its association with perioperative myocardial infarction remains controversial. Ischemic preconditioning is a novel method of myocardial protection. Methods. To answer whether aprotinin increases post-ischemic myocardial damage and also to characterize the effect of aprotinin on ischemic preconditioning, four groups of sheep were fully heparinized to keep activated clotting time readings greater than 750 seconds and subjected to 60 minutes of normothermic regional ischemia (diagonal 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 preconditioning (three 5-minute intervals of ischemia and reperfusion) before prolonged 1-hour ischemia, and group IV underwent similar ischemic preconditioning and received aprotinin. Area at risk was delineated by monastryl blue pigment, and infarction size by tetrazolium staining. Results. The ratios of weight of area at risk to left ventricular weight and left ventricular weight to body weight were constant between groups. Infarction size to area at risk ratio data demonstrated that aprotinin 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). Aprotinin also attenuates the protective effect of ischemic preconditioning (infarction size to area at risk ratio from 25% ± 4% to 41% ± 6%; p < 0.001). Conclusions. In the setting of ischemia, aprotinin increases myocardial damage. If, however, the heart is provided with protective preconditioning, then the deleterious effect of aprotinin may be neutralized. From these data we suggest that aprotinin should not be used routinely in cardiac operations unless extensive blood loss is anticipated, such as in redo open heart operations.