Neural factors in acute emetic, cardiovascular, and respiratory effects of T-2 toxin in cats.
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.
Borison
H L
HL
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Goodheart
M L
ML
D000818:Animals; D001665:Binding Sites; D001933:Brain Stem / Q000033:anatomy & histology / Q000187:drug effects; D002245:Carbon Dioxide; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D002415:Cats; D002552:Cerebral Ventricles / Q000033:anatomy & histology / Q000187:drug effects* / Q000601:surgery; D003655:Decerebrate State / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D012119:Respiration / Q000187:drug effects* / Q000502:physiology; D012717:Sesquiterpenes / Q000633:toxicity*; D013605:T-2 Toxin / Q000633:toxicity*; D013990:Tidal Volume; D014839:Vomiting / Q000139:chemically induced*
D012717:Sesquiterpenes; D002245:Carbon Dioxide; D013605:T-2 Toxin