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Effect of Various Mixtures of Diethylether, Halothane, Nitrous Oxide and Oxygen on Low Molecular Weight Iron Content and Mitochondrial Function of the Rat Myocardium
Authors:H. Van Jaarsveld   J. M. Kuyl  E. H. De Wet  D. W. Alberts  F. D. Van Der Westhuizen
Affiliation: a Department of Chemical Pathology, University of the Orange Free State, Bloemfontein, Republic of South Africab Department of Physiology, University of the Orange Free State, Bloemfontein, Republic of South Africa
Abstract:Anaesthetic drugs can induce reversible as well as irreversible changes in cell membranes and intracellular proteins as well as lipid peroxidation in the liver. Low molecular weight iron species (LMWI) can by their catalytic activity contribute to the generation of free radicals (hydroxyl radicals). Free radicals are a recognisable cause of intracellular damage. Impaired mitochondrial function is also a sign of intracellular damage, which is usually irreversible. Thus, an agent may be cytotoxic when it causes a significant increase in intracellular LMWI. Whether the LMWI arise from ferritin or is released from iron containing proteins, the same reaction occurs. As long as LMWI can undergo redox cycling, hydroxyl radicals can be formed. We investigated the effect of various mixtures of diethylether, halothane, nitrous oxide and oxygen on the intracellular LMWI content and mitochondrial function of the rat myocardium.

Hearts isolated from rats anaesthetised with diethylether showed an increase in the cytosolic LMWI compared to the control group. No increase in mitochondrial LMWI was demonstrated. Subsequent perfusion of the isolated hearts showed a further increase in the LMWI. On perfusion the mitochondrial LMWI increased in comparison with controls. Mitochondrial function was significantly impaired as measured by the QO2 (state 3), ADP/O ratio and oxidative phosphorylation rate (OPR).

Exposure of rats to 50% nitrous oxide for 15 minutes increased the myocardial LMWI, but had no effect on mitochondrial function. Exposure to room air for 30 minutes before isolating the hearts, still showed a significant increase in LMWI with no detectable change in mitochondrial function.

Halothane, on the other hand, did not have an effect on the myocardial LMWI and mitochondrial function in the experiment setup used. We therefore concluded that diethylether and nitrous oxide are potentially toxic to the myocardium and may potentiate the action of free radicals.
Keywords:Nitrous oxide  halothane  oxygen radicals  mitochondria  iron  diethylether
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