Induction of hypothermia

Rosomoff H. L. (1957) Hypothermia and cerebral vascular lesions. II. Experimental middle cerebral artery interruption followed by induction of hypothermia. AMA Arch. Neurol. Psychiatry 78,454 -64. 

Schwab et al. used mild hypothermia (33-34°C) in 20 patients with acute severe middle cerebral artery (MCA) infarction for 48-72 h and found mild hypothermia to be safe and feasible (38). Schwab subsequently reported a series of 25 patients with severe MCA infarction treated with the same protocol (39). Intracranial pressure (ICP) was monitored for 3-7 d, and was found to decrease with initiation of hypothermia. ICP increased during re warming in several patients, but not to the levels seen prior to induction of hypothermia. Pneumonia was seen in 40% of patients treated with hypothermia in this trial, which is within the expected range of occurrence in patients with prolonged ventilation (40). Shimizu et al. used mild hypothermia (33°C) in five patients with embolic infarctions involving the internal carotid artery and MCA territories. The hypothermia was maintained for 3-7 d (41). It was found to be safe, but the number of patients was too small to report any efficacy. Another acute stroke trial using convection air to induce mild hypothermia without anesthesia was found to be feasible (42). Temperatures in this trial were reduced only to 35.5°C, and shivering... 

Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001 344 556-563. 

One endeavor of risk assessment i.s to identify the threshold for a toxicological effect such as hypothermia. It seems that the threshold AChE inhibition for induction of hypothermia would be lowered if the animals were subjected to colder temperatures and more sensitive methods were used to monitor core temperature (i.e., telemetry). Must rodent. studies arc performed at ambient temperatures that are comfortable for humans (-22 °C) but are approximately 6 C below the rat. s lower critical temperature. Our database on threshold doses to achieve physiological responses to anti-ChEs as well as other toxicants could change significantly if the choice of temperatures to house and test rodents was reconsidered. 

Webster, W.S., Gemain, M.A., Edwards, M.J. (1985). The induction of microphthalmia, encephalo-cele, and other heat defects following hypothermia during the gastrulation process in the rat Teratology 31, 73-82. 

Piepgras A., Roth H., Schurer L., et al. (1998) Rapid active internal core cooling for induction of moderate hypothermia in head injury by use of an extracorporeal heat exchanger. Neurosurgery 42, 311-317 discussion 317-318. 

We recently carried out a study (40) to determine the effects of delaying induction of mild hypothermia after transient focal cerebral ischemia and to ascertain whether the neuroprotective effects of mild hypothermia induced during the ischemic period are sustained over... 

In addition to the neurotransmitter and hydroxyl radical consequences, postinjury temperature modification has been shown to affect the induction of immediate early genes/protooncogenes and influence upregulated cytokine expression. For example, hypothermia was... 

Inderbitzen B., Yon S., Lasheras J., Dobak J., Perl J., and Steinberg G. K. (2002) Safety and performance of a novel intravascular catheter for induction and reversal of hypothermia in a porcine model. Neurosurgery 50, 364—370. 

In the other study (56), 275 patients were randomized to normother-mia or hypothermia (32-34°C) over 24 h, with a median interval between restoration of circulation and hypothermic induction of 1.75 h. At 6 mo postinsult, the likelihood of a favorable outcome was significantly better in the hypothermia group (55%) compared to the normothermia group (39%, confidence interval 1.08-1.81). Mortality rates were similarly improved in the hypothermia group. 

Jeevaratnam, K., Vijayraghavan, R., Kaushik, M.P., Vaidyanathan, C.S. (1992c). Acute toxicity of methyl isocyanate in mammals. II. Induction of hyperglycemia, lactic acidosis, uraemia and hypothermia in rats. Arch. Environ. Contam. Toxicol. 19 314-18. 

Tolerance and abstinence may develop with any of the barbiturates. It has been reported that abrupt withdrawal of secobarbital (given 0.8-2.2 g/d for 6 weeks) causes both minor symptoms (tremors, anorexia, insomnia, and apprehension) and major symptoms (seizures, delirium, and hypothermia) that can persist for up to 2 weeks after discontinuation. Tolerance to barbiturates can develop within 2 weeks of treatment because of induction of hepatic microsomal enzymes (2). 

Restoration of blood flow following cardiac arrest can lead to several chemical cascades and destructive enzymatic reactions that can result in cerebral injury. These reactions include free-radical production, excitatory amino acid release, and calcium shifts, leading to mitochondrial damage and apoptosis (programmed cell death). Hypothermia can protect from cerebral injury by suppressing these chemical reactions, thereby reducing the production of free radicals. Various animal models have demonstrated improved functional recovery and reduced cerebral deflcits with the induction of mild therapeutic hypothermia. Recently, there have been two clinical trials in humans evaluating this technique. ... 

Dixon SR, Whitboum RJ, Dae MW, et al. Induction of mild systenuc hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol 2002 40 1928-1934. 

Based on the available evidence, it is considered that this classification still stands and that phenol should still be regarded as a somatic cell mutagen. It is noted that although the high dose positive micronuclei results being secondary to phenol-induced hypothermia is a plausible hypothesis, no definite conclusions about this mechanism can be drawn due to the limited nature of the available data (abstract form and lackof a confirmatory test showing that prevention of hypothermia by maintaining the animals body heat also prevents the induction of micronuclei). 

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