Enalaprilat, an Angiotensin-converting Enzyme Inhibitor, Enhances Functional Preservation During Long-term Cardiac Preservation. Possible Involvement of Bradykinin and PKC

We investigated the effect of enalaprilat (ET) on long-term preservation of cardiac explant. Isolated rat hearts (n=7/group) were pretreated with 0 to 40 n ET and stored at 0°C for 16 h. Functional viability was assessed after 30-min working reperfusion without ET. Prestorage control function (mean± ) (n=7) included heart rate (HR), 291±12 bpm; aortic flow (AF), 49.8±1.9 ml/min; coronary flow (CF), 25.2±1.3 ml/min; cardiac output (CO), 75.0±1.2 ml/min; and work, 89.4±4.7 g-m/min. Post-storage function of untreated hearts was: AF, 61%; CF, 43%; CO, 55%; work, 48% of control. ET (20 n ) enhanced AF recovery to 85%; CF, 58%; CO, 76%; work, 73% of control (P<0.05vuntreated). Hoe 140 (D-Arg-[Hyp2, Thi5,8, D-Phe7]BK) (1 n ), a bradykinin receptor antagonist, inhibited ET effect; function returned to the untreated level. Protein kinase C (PKC) inhibitors staurosporine (15 n ) and bisindolylmaleimide I (0.5μm) also blocked ET effect. After 4 h of cold storage, membrane PKC activity changed little from the prestorage level in the untreated hearts, but was elevated significantly from 52.8±5.2 pmol/min/mg to 74.7±8.2 by 20 n ET (P<0.05vuntreated). Cytosol PKC did not change during 4 h cold storage with or without ET. Neither end-storage nor end-reperfusion myocardial ATP content was affected by 20 n ET treatment. In conclusion, ET improves cardiac preservation possibly via bradykinin receptor and PKC without affecting ATP metabolism.