Intracellular acidosis and contractility in the normal and ischemic heart as examined by ³¹P NMR

³¹P was used to investigate correlations between intracellular pH (pH_i) and myocardial contractility in the normal and ischemic isolated, perfused isovolumic rabbit heart. Intracellular pH was calculated from the chemical shift of Pi in hearts perfused with phosphate-free buffer. Normal intracellular pH was 7.22 ± 0.02 (n = 15). To calibrate the relationship between pH_i and left ventricular developed pressure (LVDP), respiratory acidosis was induced by mixing 65% O₂: 30% N₂: 5% CO₂ with 65% O₂: 35% CO₂ using Krebs buffer containing 24 mm HCO₃^-. The results show that a 0.22 pH unit acidification correlates with a 50% reduction in LVDP. The correlation between pH_i and LVDP was also studied in two models of ischemia: total global ischemia and steady state partial ischemia (50% reduction of LVDP). In both ischemic conditions, a 50% lowering in LVDP correlated with only a 0.09 pH unit acidification. Thus, while intracellular acidosis may account for 40 to 50% of the depression of LVDP oberved during the early phases of ischemia, other factor must also play a role. Mass spectrometry was used to examine the potential regulatory role of tissue oxygen (P_mO₂). The model of steady-state partial ischemia was employed. Changes in LVDP and MVO₂ correlated quite closely with reductions in coronary flow. However, up to a 50% reduction in flow, pH_i remained near normal, and tissue P_mO₂ was normal or slightly elevated. These latter results suggest that an efficient autoregulatory mechanism controls both function and MVO₂ in close parallel to changes in flow. As a result, the metabolic supply/demand balance is maintained. However, beyond a 50% reduction in flow, this mechanism fails and metabolic indicies of ischemia are expressed.