FUNCTIONAL INTERACTION BETWEEN LOCAL-ANESTHETICS AND CALCIUM-ANTAGONISTS IN GUINEAPIG MYOCARDIUM .2. ELECTROPHYSIOLOGICAL STUDIES WITH BUPIVACAINE AND NIFEDIPINE

The negative inotropic effect of local anaesthetics is potentiated by several calcium antagonists in guineapig myocardium [1]. Therefore, we studied which effects on cardiac ionic currents could be responsible for this interaction. Concentration response curves for bupivacaine were studied in isolated guineapig atria and papillary muscles (slow action potentials). Effects on action potentials were assessed in the absence (n = 7 atria, n = 8 papillary muscles) or presence of nifedipine (8 x 10(-8) mol litre(-1) in n = 8 atria, 10(-8) mol litre(-1) in n = 8 papillary muscles). The effect on the Ca2+ current was assessed directly using the patch-clamp technique in guineapig ventricular myocytes. Bupivacaine reduced contractile force and upstroke velocity of atrial action potentials. Only the negative inotropic effect was potentiated in the presence of nifedipine, Force and upstroke velocity of slow action potentials were diminished by bupivacaine. Both variables were affected at significantly smaller concentrations of bupivacaine when given in combination with nifedipine. The Ca2+ current was reduced significantly by bupivacaine 5 x 10(-5) mot litre(-1) (mean - 18 (SD 7) %, n = 9). Its effect was accentuated in the presence of nifedipine 10(-9) mol litre(-1) (-47 (4) %, n = 7). Bupivacaine 3 x 10(-4) mol litre(-1) given alone exerted a comparable effect (-53 (4) %, n = 4). Variables indicative of Ca2+ channel function (contractile force, upstroke of slow but not normal action potentials, Ca2+ inward current) revealed potentiation of the effects of bupivacaine by nifedipine.