The use of a nondepolarizing cardioplegic solution for cardiac preservation has a beneficial effect on the left ventricular diastolic function.

Abstract

We have developed a nondepolarizing solution (NDS) that retards myocardial calcium accumulation during cardioplegia. This study compares 1) the membrane resting potential (Em) in Purkinje fibers during cardioplegia induced by NDS or University of Wisconsin solution (UW) at normothermia and hypothermia for 6 h, 2) left ventricular (LV) diastolic function of isolated canine hearts preserved with NDS or UW for 6- and 12 h in hypothermia to elucidate the relationship between diastolic function and myocyte physiology (n = 8, each group), and 3) the effect of Non-depolarizing solution (NDS) compared with Bretschneider's HTK solution on LV diastolic function in isolated rabbit hearts using the Langendorff model in normothermia (n = 10, each group). The membrane resting potential (Em) was as follows: NDS in normothermia, -71 mV (2 min), -65 mV (30 min), and -52 mV (60 min); NDS in hypothermia, -40 mV (1 h) and -32 mV (6 h), while UW in hypothermia 0 mV (6 h). Myocardial calcium accumulation during reperfusion in the NDS groups was minimal and significantly lower than in the UW groups after the 6- and 12 h preservations. Postreperfusion myocardial cyclic adenosin monophosphate (cAMP) and adenosin triphosphate (ATP) concentrations in the NDS groups were closer to normal than in the UW groups after the 6- and 12 h preservations. The postreperfusion myocardial Ca concentration correlated with the cAMP (r = -0.68, n = 25, P = 0.003) and cyclic guanosine monophosphate (cGMP) concentrations (r = -0.69, n = 25, P = 0.003). The left ventricular end-diastolic pressure (LVEDP) after reperfusion correlated with myocardial ATP (r = -0.65, n = 25, P = 0.003) and Ca concentrations (r = -0.68, n = 25, P = 0005). However, the parameter indicating LV elasticity (max LV -dp/dt) correlated with neither the Ca or ATP concentration following reperfusion. NDS prevented stiffness (increased LVEDP) better than HTK during normethermic cardioplegia for 30 min. These results in vitro suggest that NDS prevents myocardial Ca accumulation, depletion of ATP and cAMP, and preserves LV diastolic function, particularly stiffness after reperfusion, for up to 12 h. Furthermore, the myocardial Ca concentration is inversely correlated with the cAMP and cGMP concentrations.