Creatine phosphate: An additive myocardial protective and antiarrhythmic agent in cardioplegia

Abstract

The potential for enhancing myocardial protection by adding high-energy phosphates to cardioplegic solutions was investigated in a rat heart model of cardiopulmonary bypass and ischemic arrest. Creatine phosphate (CP) was evaluated as an additive to the St. Thomas' Hospital cardioplegic solution. Dose-response studies (CP 0 to 50 mmol/L) revealed 10.0 mmol/L as the optimal concentration which improved recovery of aortic flow and cardiac output after a 40 minute period of normothermic (37 degrees C) ischemic arrest from 21.2% +/- 5.4% and 32.8% +/- 4.6% in the CP-free control group to 82.5% +/- 3.7% and 82.6% +/- 4.2% (p less than 0.001), respectively. Creatine kinase (CK) leakage was reduced by 68.7% (p less than 0.001) in the CP group. With hypothermic (20 degrees C) ischemia (240 minutes) and multidose (every 30 minutes) cardioplegia, recoveries of aortic flow and cardiac output were improved from 33.1% +/- 8.4% and 42.2% +/- 7.7% in the CP-free control group to 77.9% +/- 4.2% and 79.6% +/- 4.3% (p less than 0.001), respectively, in the drug group. In addition to improving function and decreasing CK release, CP reduced reperfusion arrhythmias, significantly decreasing the time between cross-clamp removal and return of regular rhythm and also completely obviating the need for electrical defibrillation. 51Chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), an extracellular space marker, was used to study the disappearance of CP from the cardioplegic solution during its stasis in the heart. Upon reperfusion, two thirds of the infused dose appeared unchanged in the coronary effluent; the remainder was either degraded or accumulated by the myocardium. Despite its alleged inability to enter the myocardial cell, exogenous CP exerts potent protective and antiarrhythmic effects when added to the St. Thomas' Hospital cardioplegic solution. Although the mechanism of action remains to be elucidated, it may involve binding or uptake of the drug.