Functional interaction between local anaesthetics and calcium antagonists in guineapig myocardium: 1. Cardiodepressant effects in isolated organs.
Both local anaesthetics and calcium antagonists depress cardiac function. Therefore, we have studied the interaction of these compounds in the isolated myocardium of guineapigs. The negative inotropic effect of various local anaesthetics was investigated in left atria in the absence or presence of nitrendipine 10(-7) mol litre-1 (n = 7-8 in each group). In addition, the effect of bupivacaine was studied in the presence of several calcium antagonists. The factor by which the negative inotropic potency (EC50) of local anaesthetics was enhanced significantly in the presence of nitrendipine varied from mean 1.2 (SD 0.2) (benzocaine) to 3.0 (0.6) (bupivacaine). The EC50 of bupivacaine was lowered by all calcium antagonists. The potentiation factor varied from 1.4 (0.4) (verapamil) to 3.3 (0.6) (nifedipine). The effects of benzocaine (n = 12) and bupivacaine (n = 11) on the working heart were assessed either alone or after pretreatment with nifedipine 10(-8) mol litre-1. The effects of benzocaine on contractility remained unaltered in the presence of nifedipine, whereas the negative inotropic effect of bupivacaine increased significantly (for example, a 20% reduction in left ventricular maximum dP/dt occurred with bupivacaine 1.75 (0.16) x 10(-6) mol litre-1 alone compared with 1.1 (0.22) x 10(-6) mol litre-1 when combined with nifedipine). We conclude that the effects of some local anaesthetics, for example bupivacaine, on cardiac contractility are enhanced in the presence of calcium antagonists. The relevance of this interaction in patients remains to be determined.
Herzig
S
S
Department of Pharmacology, Hospital of the Christian-Albrechts University, Kiel, Germany.
Ruhnke
L
L
Wulf
H
H
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001566:Benzocaine / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D009568:Nitrendipine; D009543:Nifedipine; D001566:Benzocaine; D002045:Bupivacaine