Positive inotropic and toxic effects of brevetoxin-B on rat and guinea pig heart.
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 X 10(-8) and 1.87 X 10(-7) M. The toxin (10(-7) M) 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 (beta 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.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D035964:Oxocins; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D000095702:Polyether Toxins
D008387:Marine Toxins; D035964:Oxocins; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013779:Tetrodotoxin; C043466:brevetoxin B; D000095702:Polyether Toxins