Myocyte cytochrome oxidase activity and neuromuscular conduction associated with metabolic alkalemia.
Many studies have shown increased affinity of hemoglobin for oxygen during metabolic alkalemia and dependence of intramitochondrial cytochrome oxidase activity on arterial oxyhemoglobin saturation. The present studies tested the hypothesis that metabolic alkalemia produces tissue hypoxia independent of arterial oxygen desaturation. Neuromuscular conduction latency was used as an indicator of functional impairment, and was measured following electrostimulation of the sciatic nerve and recording of the electromyogram from the gastrocnemius muscle of rats anesthetized with pentobarbital sodium. To increase the affinity of hemoglobin for oxygen, sodium bicarbonate was administered in graded doses every 15 min. Statistical significance of changes was estimated by the paired Student's t test. Arterial bicarbonate ion concentration increased from 25 +/- 1.3 to 39.0 +/- 3.0 mM while arterial pH increased from 7.30 +/- 0.02 to 7.50 +/- 0.03 (P less than 0.01). Neuromuscular conduction latency increased from 1.9 +/- 0.13 to 2.7 +/- 0.18 ms (P less than 0.01). Tissue hypoxia was suggested by a greater decrease in mass spectrometric determinations of gastrocnemius muscle oxygen tension (PO2) in separate groups of control (arterial pH 7.38 +/- 0.04) and experimental (arterial pH 7.48 +/- 0.03) rats. These changes were accompanied by markedly decreased uptake of 3.3'-diaminobenzidine (DAB) by gastrocnemius muscle mitochondria, suggesting decreased intracellular activity of cytochrome oxidase and intracellular oxygen availability to myocytes in the absence of arterial oxygen desaturation.
D000471:Alkalosis / Q000201:enzymology / Q000503:physiopathology*; D000818:Animals; D001831:Body Temperature; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology*; D009469:Neuromuscular Junction / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission
D003576:Electron Transport Complex IV