Myocardial buffering capacity in ischemia preconditioned rat heads

Abstract

Brief episodes of ischemia prior to a prolonged ischemic episode, ischemic preconditioning (IPC), significantly reduce infarct size and improve postischemic functional and metabolic recovery. Although the precise mechanism of IPC has not been fully elucidated, IPC hearts consistently demonstrate less acidosis during ischemia than control hearts (Kida et al., 1991; Wolfe et al., 1993; Steenbergen et al., 1993; de Albuquerque et al., 1994). The importance of the attenuation of ischemiainduced acidosis in IPC is demonstrated by its close associati6n with infarct size reduction (Wolfe et al., 1993), and by studies wherein independent lowering of intracellular pH in preconditioned ischemic rat hearts diminishes the magnitude of metabolic and contractile improvement during postischemic recovery (de Albuquerque et al., 1994). The relatively higher intracellular pH during ischemia in ischemic preconditioned hearts could be due to reduced proton production and/or improved proton buffering capacity during ischemia. Some of the clearest evidence demonstrating reduced proton production in ischemic preconditioning comes from Murry et al. who reported lower lactate levels during ischemia in preconditioned dog hearts as compared with controls (Murry et al., 1990). Findings of reduced ischemic glycolytic proton production have been reported in other species following preconditioning, as well (Weiss et al., 1993). Kida et al., observed relatively higher intracellular pH in preconditioned hearts as compared with controls, but were the first to suggest that improved buffering capacity could also contribute to the attenuation of ischemic acidosis (Kida et al., 1991). They speculated that the increased creatine phosphate levels (creatine phosphate overshoot) following brief episodes of ischemia in preconditioned hearts could act as one of several potential proton buffers and help attenuate the extent of acidosis during subsequent ischemia. Although improved buffering capacity by this or any other mechanism could contribute to the relatively higher pH in IPC during ischemia, studies of buffering capacity in ischemic preconditioned hearts have not been reported before. Buffering .capacity is usually defined as the change in pH for a given amount of acid loading. In these studies, we used NMR spectroscopy to measure intracellular pH during both respiratory and metabolic acid loading as well as during ischemia to determine whether buffering capacity differed in ischemia preconditioned and control rat hearts.