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The Endogenous Digoxin-like Factor Enhances Bupivacaine Toxicity in Rats

Background and Objectives. The influence of the immunoreactive endogenous digoxin-like factor (IEDLF) on the systemic toxic effects of bupivacaine was studied in a rodent model. Methods. During 5 weeks, IEDLF secretion was promoted in 10 Wistar male rats by allowing them to drink saline 0.5% in place of water. Ten other animals drank desionized water (control). At the time of experimentation, the two groups of rats were mixed to allow blind observation. Anesthesia was induced with barbiturate, and controlled ventilation was started. A blood sample was drawn for IEDLF assessment just before bupivacaine was infused at a constant rate of 2 mg/kg per minute. Data were analyzed for statistical significance using Student's t -test. A p value less than 0.05 was considered significant. Results. Two rats in the saline group died during the induction of anesthesia. An IEDLF activity was found in the eight remaining rats in this group. Threshold doses of bupivacaine's toxic effects (first ventricular arrhythmia, first seizure activity, 25% fall of baseline heart rate, 25% of baseline mean arterial blood pressure, isoelectric electroen-cephalogram) were significantly lower for the rats with an endogenous digoxin-like activity. There were, however, no significant differences in the lethal dose of bupivacaine. Conclusion. In hyperoxic nonacidotic male rats, IEDLF increases the cardiac and central nervous system toxicity of bupivacaine.