INCREASED SURVIVAL IN EXPERIMENTAL RAT HEATSTROKE BY CONTINUOUS PERFUSION OF INTERLEUKIN-1 RECEPTOR ANTAGONIST

In order to assess the possible therapeutical value of interleukin-1 r eceptor antagonist (IL-1 ra) in the treatment of heatstroke, we evalua ted the effects of heatstroke on survival time (interval between onset of heatstroke and death), systemic and striatal hemodynamic changes, and extent of striatal neuronal damage in rats treated with saline or IL-1 ra. The survival time of the heatstroke rats which received norma l saline (single injection or continuous perfusion) was about 17 min. The heatstroke-induced ischemic damage to striatal neurons was due to systemic arterial hypotension, intracranial hypertension, decreased ce rebral perfusion, and striatal dopamine (DA) accumulation (275%). Rats treated with a single injection of IL-1 ra (200 mu g/kg, i.v.) immedi ately after the onset of heatstroke survived much longer (91 min) than the controls. The prolongation of survival induced by IL-1 ra was bro ught about by attenuation of the arterial hypotension, intracranial hy pertension, decreased cerebral perfusion, ischemic damage to striatal neurons, and striatal DA release value (204%). Furthermore, after cont inuous perfusion of IL-1 ra (200 mu g/kg per h, i.v.) immediately afte r the onset of heatstroke, the striatal DA release value of the rats w as further reduced to 140% while the survival time of the rats was pro longed to up to 10 h from the onset of heatstroke. Thus, it appears th at continuous i.v. perfusion of IL-1 ra is a good choice for heatstrok e therapy