Cardiovascular and lethal effects of cocaine in anesthetized dogs and guinea-pigs

Cardiovascular and lethal effects of i.v. cocaine infusion were studied in anesthetized mongrel dogs and Hartley guinea-pigs. Dogs were anesthetized with enflurane (2.25 vol%) or urethane (1500-1700 mg/kg i.v.) and guinea-pigs with urethane (1000 mg/kg i.p.). The rate of i.v. cocaine infusion was 0.91 mg/kg/min for dogs and 1.9 mg/kg/min for guinea-pigs. In spontaneously breathing dogs and guinea-pigs, death occurred by respiratory arrest, while in artificially ventilated dogs, the terminal stage of cocaine intoxication was peripheral vascular failure. Disturbances in cardiac rhythm (AV-dissociation, ectopic pacemaking activity or irregular rate) were not observed unless mean arterial blood pressure fell to levels inadequate for coronary perfusion. All animals showed an increase in the atrio-ventricular conduction interval (PR-interval). Cardiac arrest (fibrillation or standstill) was never the primary cause of death. Sympathomimetic actions of cocaine, as monitored by heart rate (HR) and mean arterial blood pressure (MAP), were not observed in dogs, while guinea-pigs exhibited only a consistent rise in MAP which was not accompanied by other signs of sympathetic activity. Changes in body temperature were not observed in either species. It is concluded that in anesthetized animals, the predominant cardiovascular and lethal effects of cocaine are the result of its local anesthetic (membrane-stabilizing) action, and that the contribution of its sympathomimetic effects, due to inhibition of neuronal uptake, is masked by its local anesthetic properties.