British Journal of Anaesthesia, 1994, Vol. 73, No. 3 357-363
© 1994 The Board of Management and Trustees of the British Journal of Anaesthesia
research-article |
Functional interaction between local anaesthetics and calcium antagonists in guineapig myocardium: 1. Cardiodepressant effects in isolated organs
Department of Pharmacology, Hospital of the Christian-Albrechts University Arnold-Heller-Strasse 7, D24105 Kiel, Germany
Department of Anaesthesiology and Intensive Care Medicine, Hospital of the Christian-Albrechts University Arnold-Heller-Strasse 7, D24105 Kiel, Germany
Correspondence to H. W.
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 107 mol litre1 (n = 78 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 108 mol litre1. 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 106 mol litre1 alone com pared with 1.1 (0.22) x 106 mol litre1 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.