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.