THE INFLUENCE OF BODY-TEMPERATURE ON INFARCT VOLUME AND THROMBOLYTIC THERAPY IN A RAT EMBOLIC STROKE MODEL

The effect of body temperature on cerebral infarcts and thrombolytic t herapy was investigated in 91 rats embolized in the right carotid terr itory. Hypothermia of 32 degrees C for 2 h with preembolic onset (n = 15) or hyperthermia of 39 degrees C for 2 h with postembolic onset (n = 22) was compared to normothermic controls (n = 17). After 48 h of su rvival, neuropathological evaluation with measurement of infarct volum e was performed. Median infarct volume in percent of affected hemisphe re volume was 11% (9-21, quartiles) in rats treated with hypothermia a lone, compared to 46% (14-59, quartiles) in normothermic controls (P = 0.04). Hyperthermia for 2 h increased median infarct volume to 65% (3 7-75, quartiles). There was a positive and significant correlation bet ween infarct volume and body temperature (R = 0.53, P = 0:0002, n = 54 ). Mortality rate was significantly higher among rats treated with hyp erthermia compared to normothermic controls (P = 0.005). A subset of 3 7 rats exposed to the same temperature regimen were treated with tissu e plasminogen activator (20 mg/kg i.v. during 45 min)2 h after emboliz ation. Judged by posttreatment carotid angiography, hyperthermic rats (n = 11) had the best degree of recanalization (P = 0.03) compared to controls (n = 17), but median infarct volume in this group was (58% (2 7-67, quartiles)) significantly larger (P < 0.02) than normothermic (2 1% (15-39, quartiles), n = 14) and hypothermic (13% (7-31, quartiles), n = 12) rats treated with thrombolytic therapy. Thrombolytic therapy following 2 h of hypothermia, could not improve the effect of hypother mia alone. We conclude, that the size of infarcts in our embolic strok e model is dependent on the body temperature during the initial phase of infarct development. Hyperthermia had a detrimental effect when com bined with thrombolytic therapy and should be avoided in clinical tria ls of this treatment.