Improved Recovery of Cardiac Function After 24 h of Hypothermic Arrest in the Isolated Rat Heart: Comparison of a Prostacyclin Analogue (ZK 36 374) and a Calcium Entry Blocker (Diltiazem)

Abstract

The effects of a stable prostacyclin analogue (ZK 36 374; 4 nM) and a calcium entry blocker (diltiazem; 50 nM) on the recovery of cardiac function after 24 h of hypothermic (10 degrees C) cardiac arrest were studied in the isolated rat heart. Recovery of the pressure-rate index of treated hearts was significantly better [59 +/- 10% for diltiazem (p less than 0.05) and 51 +/- 7% for ZK 36 374 (p less than 0.05)] than in untreated hearts (27 +/- 9%). Untreated hearts had second- and higher-degree atrioventricular block, with an average ventricular rate of 60 +/- 6% of control. All drug-treated hearts, however, were in sinus rhythm at their initial frequency without a significant alteration in PQ interval. Moreover, the incidence of severe arrhythmias was significantly reduced by ZK 36 374 (p less than 0.02) and diltiazem (p less than 0.01). ZK 36 374 reduced total purine overflow upon reperfusion (503 +/- 51 vs. 223 +/- 22 nmol min-1 g dry weight-1; p less than 0.0005). The delayed overflow of adenosine, a proposed marker of reperfusion damage, was not affected by ZK 36 374 treatment. In contrast, diltiazem had no effect on total purine overflow upon reperfusion, but nearly abolished delayed adenosine overflow. It is concluded from these results that both ZK 36 374 and diltiazem improve myocardial recovery after 24 h of hypothermic cardiac arrest.