Brief hypothermia

Several studies using brief hypothermia have not found evidence of CA1 protection (18-22). However, such discordant findings are easily explained by a mismatch between the duration of hypothermia and the severity of the ischemic insult. For example, Chopp et al. (12) found that 2 h of postischemic hypothermia reduced CA1 loss against 8 but not 12 minofischemiainrats. Similarly, other experiments indicate thatthe duration of hypothermia is critical (14,17), as very brief cooling (e.g., 0.5 h) was ineffective while somewhat longer durations were (e.g., 5 h) protective, perhaps only transiently. 

A study by Dietrich et al. (23) found that 3 h of immediate postischemic hypothermia (30°C) reduced CA1 loss at short (i.e., 3 and 7 d) but not long survival times (2 mo) after 10 min 2-VO ischemia in rats. Because all of the aforementioned studies (e.g., refs. 10-14) used short survival times, it was argued that postischemic hypothermia was, by itself, of no long-term benefit. Other work has confirmed the ephemeral nature of CA1 protection afforded by brief hypothermia (24). Likewise, a slow maturation of CA1 neuronal loss occurs following short duration (e.g., 5 min) 4-VO (vertebral cauterization + bilateral carotid artery occlusion) ischemia (25). In the 4-VO model the a-amino-3-hydroxy-... 

In summary, the severity of ischemia has a critical impact on the amount of neuroprotection obtained with postischemic hypothermia (12,27). Brief hypothermic periods (e.g., <5 h) are not very efficacious and only delay cell death. Prolonged bouts (e.g., 24 -8 h) of hypothermia... 

Iwai T., Niwa M., Yamada H., Nozaki M., and Tsurumi K. (1993) Hypothermic prevention of the hippocampal damage following ischemia in Mongolian gerbils comparison between intraischemic and brief postischemic hypothermia. Life Sci. 52,1031-1038. 

Early reports of therapeutic hypothermia for severe traumatic brain injury can be traced back to the first half of the 20th century. It is only within the last two decades that clinical studies have demonstrated that therapeutic moderate hypothermia for brief durations can improve patient outcomes following brain injury. The historical background, recent clinical experience, and mechanisms of action of moderate hypothermia are reviewed. 

Several animal models suggest that the time to initiate cooling following TBI is brief. Some rat models suggest that the therapeutic window for treatment with hypothermia is approx 25 min (41,42). These data would seem quite discouraging, as most traumatic brain injury patients do not arrive at the hospital and receive complete evaluation until significantly more time has elapsed. Even with rapid transporta-... 

In ischemia models, hypothermia (32.5°C) was found to delay the depletion of ATP within the hippocampus. It is important to note that depletion of ATP stores was only retarded, but not prevented (33). Other investigators found reductions in ATP loss when animals were cooled (46,106). Delays in ATP depletion may provide early cerebral protection during brief ischemic insults or during the initial onset of brain injury. 

If rats, during a brief hexobarbitone anaesthesia, are intravenously injected with barely sublethal doses of organo-phosphorus cholinesterase inhibitors which are able to pass the blood-brain barrier, the animals produce a hypothermia of 4-6° in 2-3 h, followed by spontaneous recovery in 12-20 h. This phenomenon has also been demonstrated in mice but not in guinea pig or rabbit. A few clinical reports of human cases of organo-phosphate poisoning mention a severe drop in the body temperature of the victims. The anticholinesterase hypothermia in the rat can partly be prevented by systemic atropine, but not by atropine methyl nitrate (for details and references, see Meeter, 1971a). 

Acute poisoning with a tricyclic antidepressant often is clinically complex brief excitement and restlessness, sometimes with myoclonus, tonic-clonic seizures, or dystonia, followed by rapid development of coma, often with depressed respiration, hypoxia, depressed reflexes, hypothermia, and hypotension. Antidepressants with strong antimuscarinic potency commonly induce an atropine-like syndrome of mydriasis, flushed dry skin and dry mucosae, absent bowel sounds. 

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