Action of Aprotinin in Myocardial Ischemia - an Investigation Using a Plasma-Free Model

Abstract

Background: The protease inhibitor aprotinin has been reported to have an anti-ischemic effect on left-ventricular myocardium in patients undergoing cardiopulmonary bypass operation. To examine the anti-ischemic properties beside its antifibrinolytic and inhibitory action on the kallikrein-bradykinin system, we investigated this substance in buffer-perfused rat hearts. Methods: 24 isolated isovolumically contracting rat hearts received a 10-minute infusion of either 10 000 units aprotinin or pure saline followed by 30 minutes of no-flow global ischemia and 45 minutes of reperfusion. Hemodynamics, high-energy phosphates, and troponin T as molecular marker of cardiac injury were studied. Results: During 15 minutes of reperfusion steady state function was identical in both groups, with a recovery of the developed left-ventricular pressure to 81.9±1.5% after protease inhibition and 83.0±2.6% in the controls. Coronary flow, myocardial oxygen consumption, and contractile reserve after maximum Ca++ Stimulation were also identical. High-energy phosphates were comparably reduced in both groups (adenine nucleotides: 3.1 ±0.3 μmol/g ww after aprotinin vs. controls 2.7 + 0.4 μmol/g ww and creatine phosphate: 6.5±0.9μmol/g ww vs. controls 4.7± 1.1 μmol/g ww). However, release of the cardiac specific marker troponin T was lower after ischemia at several measurements (p<0.05). The total release of troponin T was 44±10 ng in the aprotinin treated hearts vs. 90±17ng in the postischemic control hearts (p<0.05). Conclusions: The findings demonstrate that aprotinin in a moderate dose is effective in reducing postischemic troponin release in a non-blood perfused system. Measurement of myocardial high-energy phosphates after aprotinin use was performed for the first time and indicates that not a reduction in severity of direct myocardial ischemic intensity but a beneficial action on processes causing release of troponin is the mode of action of this effect.

Key words

Myocardial ischemia - Troponin T - Aprotinin