Mandal Maloy B, Sahu Manoj K, Mandal Sanchayan, Gupta P K
Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005.
Indian J Physiol Pharmacol. 2009 Apr-Jun;53(2):155-62.
The present study examined the interactions of local anesthetics (LA) and calcium channel blockers (CCBs) on rhythmicity of heart using in vivo and in vitro experiments. ECG recordings were made from the anesthetized rats for in vivo preparations and spontaneously beating isolated rat right atrial potential for the in vitro experiments. The in vivo experiments with LA showed dose-dependent bradycardia with lignocaine (LIG, 100-500 microg/kg) and bupivacaine (BUP, 10-100 microg/kg). BUP was 4-5 times more potent than LIG. Verapamil (VML) and diltiazem (DTZ), CCBs also produced dose (10-100 microg/kg) -dependent bradycardia. However, none of them affected the PR/QT interval or QRS complex. Further, LA-induced bradycardia was potentiated by CCBs. In addition, flattening of P-wave in ECG was observed with doses (10-25 microg/kg) of LA in the presence of CCBs. Similarly, the in vitro experiments demonstrated a concentration-dependent decrease in atrial rate by BUP or VML. The BUP-induced decrease was potentiated in the presence of VML. Thus, the results suggest that CCBs potentiate the LA-induced bradycardia by involving pacemaker activity. Further, the flattening of P-wave in ECG serves as an early indicator of the cardiotoxicity produced by these drugs.
本研究通过体内和体外实验，考察了局部麻醉药（LA）与钙通道阻滞剂（CCB）对心脏节律性的相互作用。体内实验采用麻醉大鼠进行心电图记录，体外实验则使用自发搏动的离体大鼠右心房电位。体内给予LA的实验显示，利多卡因（LIG，100 - 500微克/千克）和布比卡因（BUP，10 - 100微克/千克）可引起剂量依赖性心动过缓。BUP的效力比LIG强4 - 5倍。CCB中的维拉帕米（VML）和地尔硫䓬（DTZ）也产生剂量（10 - 100微克/千克）依赖性心动过缓。然而，它们均不影响PR/QT间期或QRS波群。此外，CCB可增强LA诱导的心动过缓。另外，在给予CCB的情况下，使用剂量为10 - 25微克/千克的LA时，心电图中P波出现低平。同样，体外实验表明，BUP或VML可使心房率呈浓度依赖性降低。在VML存在的情况下，BUP诱导的降低作用增强。因此，结果表明CCB通过影响起搏活动增强LA诱导的心动过缓。此外，心电图中P波低平可作为这些药物产生心脏毒性的早期指标。
