Carbon monoxide (CO)-induced hypoxia in mice: Evaluation as an experimental model of cerebral ischemia for drug screening.

Abstract

Abstract-An injection of 12.5 ml of carbon monoxide (CO) gas into an air-filled chamber (780 ml in volume) caused the death of the ICR or ddY mouse (6-8 weeks old) inside. The average survival time was 2.5 min for either sex of animals treated with nothing or saline and never exceeded 8 min. Pretreatment with pentobarbital Na (30 mg/kg, i.p.), hopantenate Ca (100 mg/kg, i.p.), vinpocetine (5 mg/kg, i.p. or 50 mg/kg, p.o.), flunarizine HCI (5 mg/kg, i.p.), glucose (6 g/kg, i.p.), pheno barbital (30 mg/kg, i.p.), phenytoin (20 mg/kg, i.p.), arginine HCI (100 mg/kg, i.p. or 1 g/kg, p.o.) and alanine (100 mg/kg, i.p. or 1 g/kg, p.o.) prolonged the survival time of male mice. Insofar as tested, female mice responded rather poorly to these pretreatments. Survival for longer than 8 min occurred in some of the drug-pretreated animals of either sex. To be noted is the finding that most of the animals which survived 8 min once were able to survive the second 8 min on the following day without any drug-treatment.Monitoring of the time course of carboxyhemoglobin formation revealed that the carboxyhemoglobin level reached a plateau of 70% saturation within 2 min and then gradually increased. The lethal level was about 72%. Pentobarbital decreased the formation rate but did not elevate the lethal level. The results indicate that the CO-induced hypoxia model of mice is usable for screening of drug candidates which may be effective for treatment of human ischemic diseases.

The Starving Cell: Metabolic Syndrome as an Adaptive Process

“…The once-in-vogue construct, in describing lung disease, of "blue bloaters" vs. "pink puffers" is also germane-the former reflects the relative association of hypoxemia and attendant cyanosis to development of larger body habitus. (Tobacco smoke exposure can reduce oxygen delivery 147 -and reduce mitochondrial function 148 and increase oxidative stress 149 -and is also linked to MetS 150 , despite an association to lower weight.) Ultra low calorie diets, fasting, and skipped or fewer meals should reduce MetS by the energy surfeit view.…”