LUSITROPIC CHANGES INDUCED BY ACID-BASE ALTERATIONS IN CAT PAPILLARY-MUSCLES

The present work investigates the effects of acid-base alterations upo n myocardial relaxation. Experiments were performed in cat papillary m uscles contracting isometrically at constant frequency (0.2 Hz) and te mperature (29-degrees-C). To induce intracellular alkalosis at constan t pH0, 20 mM NH4Cl were added to the perfusate. Alkalosis at variable pH0 was induced by switching from the control solution (5% CO2 -95% O2 , pH0 7.40) to a solution identical to the control one, equilibrated w ith 3% CO2 -97% O2. Acidosis was induced by switching the control perf usate to a solution equilibrated with 12% CO2 -88% O2 in which pH0 was either allowed to change or kept constant by manipulation of bicarbon ate concentration. Alkalosis produced a negative lusitropic effect eit her when pH0 was kept constant or when it was allowed to increase. For an increase in myocardial contractility of 30%, half relaxation time (T50) and time to peak tension (TTP) were prolonged 9.4 +/- 5% and 5.4 +/- 2% respectively at constant pH0 and 6.8 +/- 0.8 and 4.7 +/- 1% re spectively at variable pH0. It is suggested that this negative lusitro pic effect of alkalosis can be attributed to an increase in myofilamen t sensitivity to calcium. Either at constant or at variable pH0 acidos is decreased myocardial contractility by approximately 50%. This decre ase in contractility was accompanied by a positive lusitropic action o nly when pH0 was allowed to decrease, or when acidosis at constant pH0 was evoked in the presence of EIPA, a specific inhibitor of the Na+/H + exchanger. The results indicate that the positive inotropic effect o f a mild hypercapnic acidosis can be detected only if the degree of in tracellular acidosis was enhanced after inhibition of the Na+/H+ excha nger. Under these conditions, a decrease in myofilament sensitivity to calcium can account for the positive lusitropic effect observed.