Influence of intracellular acidosis on contractile function in the working rat heart

The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. We developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and otpimal O₂ delivery. Intracellular pH and high-energy phosphates were monitored by ³¹P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH₄Cl (extracellular pH, 7.4). The subsequent washout of NH₃ from the cytosol generated a slight acidosis (from intracellular pH 7.0 to 6.8) which was associated with little change in the determinants of O₂ consumption (rate-pressure product) and O₂ delivery (coronary flow). Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. Results were qualitatively similar at different external [Ca²⁺] (1.75, 2.5, 3.15 mM) and preload (12 or 21 cmH₂O) but were most prominent at the lowest external [Ca²⁺] and left atrial pressure. In contrast to this model of isolated intracellular acidosis, hearts subject to a respiratory (extracellular plus intracellular) acidosis showed a marked reduction in pressure development. It was concluded that 1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular achidosis, and 2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.