CARDIOVASCULAR AND CENTRAL-NERVOUS-SYSTEM TOXICITY OF BUPIVACAINE IN HYPERTENSIVE AND VASOPRESSIN-DEFICIENT RATS

Background and Objectives. The authors compared the toxic profile of b upivacaine in Sprague-Dawley rats (normotensive, normal vasopressin tu rnover), spontaneously hypertensive rats (hypertensive, elevated vasop ressin turnover) and Brattleboro rats (normotensive, deficient vasopre ssin turnover). Methods. The animals were instrumented (ECG, EEG, arte rial and venous catheters, tracheostomy, and rectal thermoprobe) under 1%-1.5% halothane in oxygen. Rats were then paralyzed with pancuroniu m (1.0 mg/kg) intravenous and ventilated with 0.5% halothane, 30% oxyg en, and 70% nitrous oxide. After a 30 minute stabilization period, bup ivacaine was infused at 2 mg/kg/minute. The doses required to produce the following toxic endpoints were determined: arrhythmia, seizure, is oelectric EEG, and asystole. Systolic and diastolic blood pressure and heart rate were measured at baseline, and at each endpoint. Results. In spontaneously hypertensive rats, doses of bupivacaine producing sei zure, isoelectric EEG, and asystole were equal to or higher than for t he Sprague-Dawley rats. The only difference between these strains of r ats, suggesting enhanced sensitivity of spontaneously hypertensive rat s to bupivacaine toxicity, was a lower arrhythmic threshold and a dram atic fall in mean blood pressure in these animals during the first 5 m inutes of the infusion, as opposed to a slight pressor response in the Sprague-Dawley and Brattleboro rats. However, mean blood pressure rem ained at a higher level in spontaneously hypertensive rats and the Bra ttleboro rats than in Sprague-Dawley rats throughout the infusion. For arrhythmia, the Brattleboro rats and Sprague-Dawley rats required a s ignificantly higher dose than the spontaneously hypertensive rats. For seizure, the Brattleboro rats required a significantly higher dose th an the spontaneously hypertensive and the Sprague Dawley rats. For iso electric EEG, the spontaneously hypertensive rats required a higher do se than the Sprague-Dawley rats. For asystole, the doses of bupivacain e were not significantly different for the three strains. Conclusions. The percentage of infusion time spent in seizure activity (time of is oelectric EEG-time of seizure) during the infusion was significantly l onger in the spontaneously hypertensive rats than in the Brattleboro r ats and the Sprague-Dawley rats. These differences might be due, in pa rt, to lower brain turnover of the excitatory peptide, vasopressin, wh ich are high in the spontaneously hypertensive rats and near zero in t he Brattleboro rats.