Preischemic hyperglycemia leads to delayed postischemic hyperthermia.
OBJECTIVE
Temperature alterations are known to influence the outcome of transient ischemia, even when instituted in the postischemic period. Since preischemic hyperglycemia aggravates ischemic brain damage, the question of whether hyperglycemic animals become hyperthermic arose. To explore this possibility, we measured body temperature telemetrically in normoglycemic and hyperglycemic rats subjected to 10 minutes of forebrain ischemia at a body (and brain) temperature of 37 degrees C.


METHODS
Isoflurane-anesthetized animals were subjected to 10 minutes of forebrain ischemia under normoglycemic or hyperglycemic conditions. Temperature changes after ischemia were measured by means of a telemetric temperature coil.


RESULTS
In normoglycemic animals, temperature decreased to 35.6 +/- 1.1 degrees C (mean +/- SD) during the first 4 hours of recovery, after which it gradually increased to normal values (38 degrees C). Hyperglycemic animals behaved differently in that they remained normothermic for approximately 10 hours during recovery and later became hyperthermic, with core temperatures rising above 39 degrees C. The rise in temperature was not due to the osmotic load of the glucose administered because infusion of mannitol, which gave a comparable increase in plasma osmolality, failed to cause delayed postischemic hyperthermia. Excessive hypercapnia during ischemia in normoglycemic animals, which produces cerebral acidosis of a magnitude similar to that of hyperglycemia and is known to aggravate ischemic lesions, likewise failed to induce hyperthermia. When post-ischemic seizures ensued in hyperglycemic subjects, temperature was 39.8 +/- 0.6 degrees C. Animals with seizures invariably died. To evaluate the influence of postischemic hyperthermia on the outcome, an additional series of experiments was performed in which delayed hyperthermia was avoided by gentle cooling (n = 6) or by acetaminophen administration (n = 5). Although these procedures prevented delayed hyperthermia, they neither blocked seizure induction nor affected the fatal outcome. Postischemic seizures developed when the core temperatures of animals were 37.9 +/- 0.1 degrees C and 37.8 +/- 0.2 degrees C in the cooled and acetaminophen-treated groups, respectively.


CONCLUSIONS
The results suggest that both delayed hyperthermia and delayed seizures in hyperglycemic animals are caused by the aggravated damage incurred by these animals during or immediately after the ischemic insult.
Uchino
H
H
Laboratory for Experimental Brain Research, University of Lund, Sweden.
Lundgren
J
J
Smith
M L
ML
Siesjö
B K
BK
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D002545:Brain Ischemia / Q000503:physiopathology*; D005334:Fever; D005947:Glucose / Q000008:administration & dosage; D006935:Hypercapnia / Q000503:physiopathology; D006943:Hyperglycemia / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D016548:Prosencephalon / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology; D013997:Time Factors
D000082:Acetaminophen; D008353:Mannitol; D005947:Glucose