Neurological analysis of respiratory, cardiovascular and neuromuscular effects of brevetoxin in cats

Abstract

Effects of brevetoxin were evaluated in cats anesthetized with pentobarbital under conditions of controlled end-expiratory pCO2 and constant body temperature. Recordings were made of arterial blood pressure, heart rate, respiratory pattern, diaphragm EMG, evoked tibialis muscle twitch and evoked contraction of the nictitating membrane. Electrical stimulation was employed for periodic excitation of the medullary respiratory center, the phrenic nerve, the peroneal nerve and the cervical sympathetic nerve. Brevetoxin was prepared at a concentration of 1.0 mg/ml in an aqueous medium of 2.5% ethanol plus 2.5% Emulphor 620 (General Aniline and Film Corp., New York). Small i.v. bolus injections of the toxin (40 micrograms/kg) evoked, without tachyphylaxis, the Bezold-Jarisch reflex triad of bradycardia, hypotension and bradypnea. This effect was essentially abolished by vagotomy. Continued injections then resulted in pressor reactions and tachycardia, along with the development of respiratory dysrhythmia. Large doses of brevetoxin (160 micrograms/kg i.v.) caused somatomotor seizures accompanied by severe hypertension, that occurred even after decerebration and cervical spinal cord transection. Cranial intra-arterial and intra-cerebroventricular injections of brevetoxin produced hypertension and respiratory depression more effectively than did i.v. injections. Systemic cumulation of the toxin, with the respiration supported artificially, caused death from cardiovascular collapse, without significant blockade of neuromuscular and ganglionic transmission. It is concluded that brevetoxin exerts its major toxic effects on the circulation and respiration through reflex and central actions, largely sparing peripheral motor mechanisms.