Ea. Bukhari et al., DOES APROTININ INCREASE THE MYOCARDIAL DAMAGE IN THE SETTING OF ISCHEMIA AND PRECONDITIONING, The Annals of thoracic surgery, 60(2), 1995, pp. 307-310
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.