Cardiovascular effects of brevetoxins in dogs.

In anesthetized spontaneously breathing dogs, brevetoxin caused dose-dependent periods of apnea and, at high doses, respiratory arrest. In artificially ventilated dogs, i.v. brevetoxin caused complex dose-related cardiovascular changes consisting of: (1) bradycardia; (2) triphasic blood pressure changes, sequentially characterized by depressor/pressor/depressor phases; (3) cardiac arrhythmias including ventricular fibrillation; (4) muscle fasciculations. Prevention of bradycardia by atropine, vagotomy or ganglionic blockage unmasked a tachycardic action of the toxin. Ganglionic blockade, but not atropine or vagotomy, reduced the initial depressor effect of toxin. Phentolamine prevented the toxin-induced initial hypotension and secondary hypertension. Propranolol prevented the tachycardic and late depressor effects of toxin. In reserpinized dogs, low doses of toxin caused muscle fasciculations but none of the above cardiovascular effects; large doses caused bradycardia preventable by atropine, but not by vagotomy or chlorisondamine. These results suggest that brevetoxin: elicits the Bezold-Jarisch effect, i.e. initial hypotension, bradycardia and apnea; releases catecholamines, probably adrenal epinephrine, causing tachycardic, secondary pressor and late depressor effects; in large doses, releases vagal acetylcholine; -induced catecholamine and acetylcholine release is not nicotinic; produces effects, like those reported for veratridine, attributable to a common action on excitable membranes.