Objective To study the possible mechanisms of the protective effect of ginsenoside-Rd injection, a preparation of Chinese herbal medincine, on the central nervous system(CNS) and cardiac toxicities of bupivacaine in rats. Methods Thirty male Sprague-Dawley rats, weighing 280 to 320 g, were randomly assigned to three groups: control group (C), ginsenoside-Rd group (R), and solvent group (S) (n=10 each). Animals in group R received ginsenoside-Rd injection 30 mg/kg intraperitoneally 30 min before intravenous infusion of bupivacaine whereas rats in group C and S received an equal volume of saline injection or ginsenoside-Rd solvent (propylene glycol) ,respectively. Lead II in the electrocardiogram (EEG) was continuously monitored. The femoral artery was cannulated for direct measurement of arterial blood pressure and for collection of blood samples. After the basic parameters (arterial blood pressure, heart rate, and arterial blood gases) were recorded, 0.5% bupivacaine was infused intravenously at a rate of 2 mg/(kg·min) into both groups until asystole. The time of bupivacaine-produced convulsions, arrhythmia (QRS prolongation in ECG), circulation collapse (MAP≤40 mmHg) ,and asystole were determined before the cumulative dose of bupivacaine was calculated at the corresponding time points. During bupivacaine infusion, bupivacaine-produced convulsions, and circulation collapse (MAP≤40 mmHg), 1 ml blood sample was drawn and the NO and NOS activities were tested. Results In the ginsenoside-Rd group, the cumulative doses of bupivacaine that produced convulsion, arrhythmia and circulation collapse were significantly higher than those in the control group. The NOS activity was significantly decreased and the NO activity was significantly increased after the onset of convulsion in both groups. The NOS and NO activities in group R were both significantly higher than those in group C and group S during convulsion and circulation collapse. Conclusion Pretreatment with ginsenoside-Rd injection can remarkably reduce the toxicity of bupivacaine to the central nervous and cardiac systems in rats probably by increasing the NO and NOS activity.
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