Direct and reflex cardiovascular effects of trichothecene mycotoxins

Intravenous injection of T-2 toxin or roridin-A (2 mg/kg) into pentobarbital-anesthetized (30 mg/kg) dogs produced, respectively, decreased systolic pressure within 30 min and atrio-ventricular block within 60 min. Within 45 +/- 15 min after injection of each toxin heart rate increased and remained elevated for at least 4 hr. The increase in sinus rate was reduced by 50% when dogs were pretreated with i.v. propranolol--HCl (5 mg/kg); pretreatment with atropine sulphate (5 mg/kg) did not alter the effect of the trichothecenes. Upon administration of T-2 toxin or roridin-A (30 mg/l) to isolated arterially perfused canine right atria, sinus rate decreased by 12% and 28%, respectively, and sinus node cell diastolic potentials became more negative by 7% and 10%, respectively. Sino-atrial block observed in 50% of the isolated atrial preparations perfused with roridin-A disappeared when toxin perfusion was discontinued. Perfusion with T-2 toxin or roridin-A produced no significant effects on atrial muscle cell action potentials. The cardiovascular response to systemic trichothecenes was hypotension followed by propranolol-sensitive tachycardia. The direct effects on conduction system cells may contribute to the overall deleterious action on the cardiovascular system.