Respiratory acid-base changes and myocardial contractility: Interaction between calcium and hydrogen ions

Abstract

The mechanism whereby respiratory acid-base changes alter myocardial contractility is poorly understood. Accordingly, 46 cat right ventricular papillary muscles contracting isometrically at 30°C were studied while varying both the pH and [Ca 2+] of the bathing medium. The pH changes were induced by varying the PCO 2 of the gassing mixture. A decrease in pH from 7.45 to 7.10 in the presence of 2.5 m m Ca 2+ caused a rapid fall in active force and rate of force development ( dF dt ) to levels 76% of control followed by a gradual recovery to approximately 89% of control during a 60 min observation period despite continued acidosis. Increasing the [Ca 2+] to 5.0 m m markedly attenuated the negative inotropic effects of hypercarbic acidosis. Increasing the pH from either 7.10 to 7.45 or 7.45 to 7.75 caused a rapid 15% increase in active force and dF dt followed by a return to near control levels after 60 min. The biphasic contractile response to either respiratory acidosis or alkalosis was not influenced by pretreating the muscles with 1 × 10 −6 m propranolol. In 10 additional muscles series elastic load-extension relations at varying pH levels were determined using standard quick-release techniques. Respiratory acid-base changes did not alter the measured series elastic properties. These findings indicate that the contractile effects produced by carbon dioxide-induced pH alterations are exerted at the level of the contractile element and that the muscle has the intrinsic capacity to attenuate these inotropic effects with time. Furthermore, our results suggest that the contractile effects produced by changing [H +] may involve an interaction with Ca 2+ at a sarcolemmal or intracellular binding site.