Search

Experiments were performed on pentobarbital-anesthetized cats to test the hypothesis that hypovolemia rather than cardiac failure is responsible for the acute lethal toxicity of the trichothecene mycotoxin, T-2 toxin (T2T). Measurements were made on mean arterial blood pressure (MAP), arterial pulse pressure (PP), and heart rate (HR) in eight otherwise untreated cats given T2T (2 mg/kg iv) and in three cats similarly injected with T2T but then transfused with plasma and blood. The transfusions to their available extent significantly delayed or counteracted the development of mycotoxic shock (i.e., depressed MAP and PP) and prevented or reversed a rise in the hematocrit. HR remained stable under all conditions. Plasmapheresis followed by whole-blood removal was found best to simulate mechanistically the mycotoxic shock syndrome in six blood donor cats free of T2T. It is concluded that hypovolemia with polycythemia resulting from plasma leakage and internal bleeding accounts for acute lethal T-2 mycotoxicosis.

T-2 toxin, a trichothecene mycotoxin, was injected iv or ip in the single lethal dose of 2 mg/kg. Vomiting was elicited in normal and decerebrate cats with an average onset time of 26.6 min. Chronic ablation of the area postrema significantly delayed the emetic latency to 304 min. Polygraph recording revealed a steady decline in mean arterial blood pressure and pulse pressure to an extreme shock level resulting in death after 5 to 15 hr. Heart rate varied unremarkably throughout the course of circulatory failure, and the cardiac beat persisted after respiratory arrest. No protection against the lethal response was afforded by midbrain decerebration, area postrema ablation, section of the carotid sinus and vagus nerves, and high spinal cord transection supported with artificial ventilation. Effects of T-2 toxin on central and reflex control of breathing were evaluated through changes in VT/FACO2 and f/VT relationships generated by delivery of CO2 enriched gas for inhalation. Central CO2 responsiveness was well maintained under all tested neurological conditions up to the stage of terminal collapse with late decreases in delta VT/delta FACO2 gain and FACO2 setpoint. A toxin-induced progressive increase in resting frequency and an associated decrease in delta f/delta VT gain was found in unanesthetized decerebrate cats, though resting f did not change remarkably in the anesthetized brain-intact cats. In vagotomized brain-intact cats, the delta f/delta VT gain was sustained at zero. These findings indicate that T-2 toxin exercised minimal influence on the brain stem CO2-VT regulator but it caused an acceleration of the central respiratory oscillator after interruption of forebrain connections.