Acute toxicity of tedisamil, a new potassium channel blocking drug.

The acute intravenous toxicity of tedisamil, a new potassium channel blocker, was assessed by infusing it at various rates (1.5 to 10 mg/kg/min.) to ventilated or spontaneously breathing rats subjected to blockade of their peripheral somatic and autonomic nervous systems. The lethal doses for ventilated rats (including pithed animals) were 2-3 times higher than those for spontaneously breathing animals. In spontaneously breathing rats death appeared to be due to respiratory depression which was possibly of central origin since the lethality of tedisamil was not markedly altered by vagotomy, bilateral carotid artery ligation, nor by autonomic nervous system blockade. On the other hand, in all of the artificially ventilated groups, death occurred at higher doses and was related to direct cardiac actions, possibly involving blockade of cardiac potassium and sodium channels. The cardiovascular responses to infusions of tedisamil included tachyarrhythmias, bradycardia, blood pressure changes, increased QRS width and Q-T interval duration. Arrhythmias occurred at sublethal doses and were eliminated by autonomic blockade and pithing. However, the bradycardia, ECG and blood pressure changes induced by tedisamil infusions were unaltered by the various treatments. Thus tedisamil may induce arrhythmias by actions on the autonomic system.

Serum resistance and hemagglutination ability of marine vibrios pathogenic for fish.

Representative strains of marine vibrios pathogenic for fish were shown to be resistant to the bactericidal activity of normal (nonimmmune) rainbow trout (Salmo gairdneri) serum, and loss of this resistance coincided with a marked reduction in virulence. Thermal lability and a requirement for Mg2+, but not for Ca2+, suggested that a mechanism for serum killing was the alternative complement pathway. In the case of Vibrio anguillarum, serum resistance was not coded for by the virulence plasmid pJM1. Additional testing showed that these pathogenic vibrios were able to agglutinate a variety of eucaryotic cells and that selected strains agglutinated trout erythrocytes; however, a correlation between strain virulence and the ability to agglutinate fish erythrocytes was not apparent. Moreover, whereas mannose was found to inhibit the agglutinating activity of several strains, two of the high-virulence strains displayed a transient, mannose-resistant hemagglutinating activity. No relationship between the carriage of pJM1 by the V. anguillarum strains and hemagglutinating activity was demonstrable.