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

Date Published: April 11, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Solmon Yang, Tserendorj Uugangerel, In-ki Jang, Hyung-chul Lee, Jong Min Kim, Byeong-Cheol Kang, Chong Soo Kim, Kook-Hyun Lee.


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.

Partial Text

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.

This study was approved by the Institutional Animal Care and Use Committee of Seoul National University Hospital (07-0167). Twelve New Zealand white rabbits (about 3 kg) were sedated with ketamine 15 mg/kg and xylazine 10 mg/kg intramuscularly. A 22-gauge venous catheter was placed into the marginal ear vein. The trachea was intubated with a 3.0 mm cuffed tube; thereafter, vecuronium 0.2 mg/kg was injected IV, followed by 0.02 mg/kg at 30 min intervals. The animals were placed in a supine position and mechanical ventilation was accomplished with a Servo 900C ventilator (SIEMENS, Erlangen, Germany) to maintain normocarbia at a fraction of inspired oxygen (FIO2) of 0.3. Anesthesia was maintained with a continuous infusion of sodium pentobarbital 5 mg/kg/hr. Ringer’s lactate solution was infused at a rate of 10 mL/kg/hr. Rectal temperature was maintained at 38-39°C with a heating pad. The carotid artery was cannulated for arterial pressure monitoring and blood gas sampling and the jugular vein for central venous pressure (CVP) monitoring and drug administration. Lead II of the electrocardiogram (ECG) was recorded continuously. The heart was exposed through the midline sternotomy for internal cardiac massage.

The two groups were comparable with respect to baseline hemodynamic variables (Table 1) and hemoglobin concentration (11.4 ± 0.8 mg/dL of C group 10.4 ± 1.4 mg/dL of I group). The time needed to CVC was 13 ± 6 sec in the C group, and 17 ± 12 sec in the I group. All animals survived by the internal cardiac massage delivered at the onset of CVC till the time of ROSC.

We designed this study to observe the insulin effect on the recovery of cardiac hemodynamics and conduction during resuscitation after a bolus injection of bupivacaine in rabbits. The results showed that the recovery of ventricular contraction and conduction was enhanced after the insulin administration as compared with the control group during cardiac compression.