Insulin Facilitates the Recovery of Myocardial Contractility and Conduction during Cardiac Compression in Rabbits with Bupivacaine-Induced Cardiovascular Collapse

Bupivacaine inhibits cardiac conduction and contractility. Insulin enhances cardiac repolarization and myocardial contractility. We hypothesizes that insulin therapy would be effective in resuscitating bupivacaine-induced cardiac toxicity in rabbits. Twelve rabbits were tracheally intubated and midline sternotomy was performed under general anesthesia. Cardiovascular collapse (CVC) was induced by an IV bolus injection of bupivacaine 10？mg/kg. The rabbits were treated with either saline (control) or insulin injection, administered as a 2？U/kg bolus. Internal cardiac massage was performed until the return of spontaneous circulation (ROSC) and the time to the return of sinus rhythm (ROSR) was also noted in both groups. Arterial blood pressure, and electrocardiography were continuously monitored for 30？min and plasma bupivacaine concentrations at every 5？min. The ROSC, ROSR and normalization of QRS duration were attained faster in the insulin-treated group than in the control group. At the ROSC, there was a significant difference in bupivacaine concentration between two groups. Insulin facilitates the return of myocardial contractility and conduction from bupivacaine-induced CVC in rabbits. However, recovery of cardiac conduction is dependent mainly on the change of plasma bupivacaine concentrations. 1. Introduction Resuscitation following bupivacaine-induced cardiovascular collapse (CVC) is difficult and often resistant to conventional treatment [1]. Bupivacaine blocks cardiac Na+ channel [2, 3] and transient outward K+ currents [4]. Increased ECG intervals [5] and decreased R-wave amplitude in lead II [6] are shown by the bupivacaine infusion. Bupivacaine also decreases the maximal rate of depolarization in Purkinje fibers [7]. Alteration of Ca++ recruitment from sarcoplasmic reticulum [8] and mitochondrial ATP production [9] are related to the deterioration of myocardial contractility by bupivacaine. Previous experiments have shown that insulin might be effective in reversing bupivacaine-induced cardiac depression probably by enhancing transient outward K+ current, Ca++ transport activity of sarcoplasmic reticulum, and improving myocardial energetics [5, 10]. In contrast, Stehr et al. demonstrate that insulin has a significant positive inotropic effect without affecting electrophysiologic parameters at a fixed bupivacaine concentration in an in vitro study [11]. Because bupivacaine impairs ventricular conduction in a dose-dependent manner and QRS widening has been shown as a function of bupivacaine concentration in an isolated rabbit heart model [12], we