Lusitropic changes induced by acid base alterations in cat papillary muscles

The present work investigates the effects of acid-base alterations upon myocardial relaxation. Experiments were performed in cat papillary muscles contracting isometrically at constant frequency (0.2 Hz) and temperature (29°C). To induce intracellular alkalosis at constant pH_o, 20 mM NH₄CI were added to the perfusate. Alkalosis at variable pH₀ was induced by switching from the control solution (5% CO₂ -95% O₂, pH_o 7.40) to a solution identical to the control one, equilibrated with 3% CO₂ -97% O₂. Acidosis was induced by switching the control perfusate to a solution equilibrated with 12% CO₂ -88% O₂ in which pH_o was either allowed to change or kept constant by manipulation of bicarbonate concentration. Alkalosis produced a negative lusitropic effect either when pH_o was kept constant or when it was allowed to increase. For an increase in myocardial contractility of 30% half relaxation tme (T₅₀) and time to peak tension (TTP) were prolonged 9.4 ± 5% and 5.4 ± 2% respectively at constant pH_o and 6.8 ± 0.8 and 4.7 ± 1% respectively at variable pH_o. It is suggested that this negative lusitropic effect of alkalosis can be attributed to an increase in myofilament sensitivity to calcium. Either at constant or at variable pH_o acidosis decreased myocardial contractility by approximately 50% This decrease in contractility was accompanied by a positive lusitropic action only when pH_o was allowed to decrease, or when acidosis at constant pH_o was evoked in the presence of EIPA, a specific inhibitor of the Na⁺/H⁺ exchanger. The results indicate that the positive inotropic effect of a mild hypercapnic acidosis can be detected only if the degree of intracellular acidosis was enhanced after inhibition of the Na⁺/H⁺ exchanger. Under these conditions, a decrease in myofilament sensitivity to calcium can account for the positive lusitropic effect observed.