Positive Inotropic and Toxic Effects of Brevetoxin-B on Rat and Guinea Pig Heart
Resource
Toxicol and Applied Pharmacology, v.76, p.296-305
Journal
Toxicol and Applied Pharmacology
Journal Volume
v.76
Pages
296-305
Date Issued
1985
Date
1985
Author(s)
Abstract
Brevetoxin-B (GbTX-B), a cyclic polyether purified from the marine dinoflagellate Gymnodinium breve, produced positive inotropic and arrhythmogenic effects on isolated rat and guinea pig cardiac preparations at concentrations between 1.25 × 10-8 and 1.87 × 10-7m. The toxin (10-7m) transiently increased left ventricular +dP dt, hydraulic work, and oxygen consumption of paced working rat hearts, then reduced these variables during continuous exposure. Brevetoxin-B exerted a much smaller positive inotropic effect on working guinea pig hearts, but produced a marked and sustained inotropic effect on guinea pig left atria. The toxin also produced arrhythmias in rat and guinea pig hearts, characterized by ventricular tachycardia and A-V blockade. Sympatholytic procedures (β blockade or reserpine pretreatment) partially blocked the positive inotropic effects, and eliminated the ventricular tachycardia, but not the A-V blockade. Tetrodotoxin markedly inhibited the positive inotropic effect of GbTX-B. Brevetoxin-B did not inhibit guinea pig cardiac Na,K-ATPase activities. The results show that GbTX-B is a potent cardiotoxin and suggest that GbTX-B exerts positive inotropic and arrhythmogenic effects by increasing sarcolemmal sodium permeability, and by releasing catecholamines from sympathetic nerve endings. © 1984.
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