Abstract
We examined the hypothesis that an increase in the myocardial cyclic adenosine monophosphate (cAMP) by a phosphodiesterase III inhibitor, E-1020, may ameliorate the hemodynamic and biochemical changes in rabbit hearts after cardioplegic arrest, and that this enzyme-mediated process is temperature-sensitive. Sixty-one male Japanese white rabbits weighing 2.8 to 3.5 kg were used. Isolated hearts were prepared for modified Langendorff circulation using modified Krebs-Henseleit bicarbonate Solution bubbled with a 95% O2- 5% C2 gas mixture. Thirty or sixty minutes of cardioplegia at 37°C, or thirty minutes of cardioplegia at 15°C was followed by normothermic reperfusion for 60 minutes. E-1020, 0.1 mmol/L was added to the cardioplegic Solution (Bretschneider's HTK Solution). The left-ventricular function was measured with a latex balloon placed in the leftventricular cavity. The myocardial cAMP was higher, the total myocardial calcium was lower in hearts with E-1020 than in hearts with HTK alone (p < 0.05). E-1020 at 0.1 mmol/L did increase the myocardial concentration of cAMP and the functional recovery, and prevented the increase in the myocardial total calcium. Temperature affected the myocardium to preserve myocardial concentrations of adenine nucleotide Compounds and cAMP. Our results suggest that a 0.1 mmol/L E-1020 adjunct to HTK Solution at 37°C completely prevents left-ventricular functional depression during 30 min of cardioplegia induced with non-oxygenated HTK, but decreases its potential efficacy at 15°C. The protective effects disappear if the ischemic period lasts 60 min at 37°C.
Key words
Phosphodiesterase inhibitor - Cardioplegia - Temperature - Reperfusion - Cyclic nucleotide
