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C. B. Templeton , M. A. Poli and R. Solow . Prophylactic and therapeutic use of an anti-brevetoxin (PbTx-2) antibody in conscious rats. Toxicon27, 1389–1395, 1989.—A polyclonal antiserum was investigated for prophylactic and therapeutic use in the treatment of brevetoxin intoxication. Conscious, tethered male rats were pre-treated with 1 ml of anti-brevetoxin IgG (PbAb) or control IgG by a 10 min infusion, then given brevetoxin (25 μg/kg) by a 1 hr infusion. Rats pre-treated with control IgG demonstrated signs of brevetoxin intoxication; these signs were absent in rats pre-treated with PbAb. In therapy studies, rats were infused for 1 hr with 100 μg/kg brevetoxin, followed immediately by 2 ml of either PbAb or control IgG. During toxin infusion, both groups showed signs of brevetoxin intoxication. Rats treated with control antibody died within 6 hr. In rats treated with PbAb, respiratory rates began to return toward baseline almost immediately, and fewer neurological signs developed. After 24 hr, nearly all neurological signs had disappeared and both core and peripheral temperatures had returned to normal. There was a time differential between two groups of signs, suggesting high and low accessibility compartments for the antibody. These compartments probably represent central and peripheral nervous system. All animals treated with PbAb survived at least 8 days. These results suggest that PbAb has both therapeutic and prophylactic potential in the treatment of brevetoxin intoxication. Further, because of the differential in efficacy in reversing central and peripheral nervous system signs of brevetoxin intoxication, it provides useful new information on the mechanism of action of this toxin.

The cardiorespiratory effects of various doses of brevetoxin (0-100 micrograms PbTx-2/kg) were studied in conscious, tethered rats, After surgical preparation and a 24 hr recovery, toxin or vehicle was infused into the tethered, awake rats for 1 hr. They were then monitored for 6 hr or until death. Toxin-infused rats had decreased core and peripheral temperatures and decreased respiratory rates; these values were all low in the 100 micrograms/kg group at the time of death. Blood gas values remained within normal limits, except terminally. Electrocardiographic (ECG) disturbances, noted in all groups given greater than or equal to 25 micrograms/kg, included heart block, premature ventricular contractions and idioventricular rhythms. It was concluded that brevetoxin causes changes in cardiac conduction and multiple changes in nervous system function.