Differential effects of L-propionylcarnitine on the electrical and mechanical properties of guinea pig ventricular muscle in normal and acidic conditions

Abstract

We studied the effects of L-propionylcarnitine (PC) on transmembrane action potentials and isometric contractile tension in isolated guinea pig ventricular papillary muscles. The effects of 5 concentrations of PC (10(-5), 10(-4), 10(-3), 10(-2) and 3 X 10(-2)M) were examined in both normal (pH 7.4) and acidic (pH 6.9) conditions. The concentrations of 10(-5) to 10(-2)M had no significant effect on action potential amplitude, maximum upstroke velocity of phase 0 and resting potential, in either condition. At pH 7.4, action potential duration (ADP) was significantly (P less than 0.05) or insignificantly shortened by the drug depending upon the concentration used. At pH 6.9, however, the APD was prolonged by moderate PC concentrations (10(-3) and 10(-2)M), in which the effective refractory period (ERP) was also lengthened, associated with an increased ERP/APD ratio. In both pH conditions, the highest concentration (3 X 10(-2)M) significantly (P less than 0.05) decreased all these action potential parameters. PC had a biphasic effect on the developed tension. In both pH conditions, low PC concentrations (10(-5) to 10(-3)M) produced an initial augmentation of the contraction, followed by subsequent reduction. The initial augmentation disappeared by pretreatment with reserpine or propranolol, suggesting the involvement of beta-adrenoceptors. In the steady state, all PC concentrations produced a negative inotropic effect at pH 7.4, while at pH 6.9 only high concentrations (10(-2)M and 3 X 10(-2)M) had this effect. These results suggest that the effects of PC in an acidic condition differ considerably from those in a normal pH condition and that limited concentrations of PC (10(-3) to 10(-2)M) may prevent re-entrant arrhythmias from developing under acidic conditions via lengthening of the ERP, without deleterious effects on the contractile force.