HYPERTHERMIA NULLIFIES THE AMELIORATING EFFECT OF DIZOCILPINE MALEATE(MK-801) IN FOCAL CEREBRAL-ISCHEMIA

The present study was inspired by two previous findings from the labor atory. The first was that dizocilpine maleate (MK-801) fails to reduce infarct size when the middle cerebral artery (MCA) is permanently occ luded by an intraluminal filament technique in rats. In seeking the re asons for this we measured temperature and found that the body tempera ture of occluded animals increases to 39.0-39.5 degrees C during the f irst 2-3 h. In order to explore whether the rise in temperature was re sponsible for the lack of effect of MK-801, two groups of animals were studied, both containing animals which were subjected to 2 h of trans ient MCA occlusion and given MK-801 15 min before, as well as 6 and 24 h after ischemia. In one group, temperature was allowed to rise spont aneously during ischemia (39.0-39.5 degrees C). In the other, body tem perature was maintained close to normal during ischemia, and for the f irst 6 h postischemically, by cooling of the ambient air. Infarct volu me was assessed by triphenyltetrazolium chloride staining after 48 h o f recovery. The results showed that MK-801 failed to reduce infarct si ze in animals whose body temperature rose during ischemia. In contrast , the drug markedly reduced infarct volume in temperature-controlled a nimals; in fact, 5/8 animals had no infarcts but selective neuronal da mage only. The results suggest that amelioration of focal ischemic dam age cannot be expected if body and brain temperature is allowed to ris e above normal.