Myocyte cytochrome oxidase activity and neuromuscular conduction associated with metabolic alkalemia |
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| Authors: | R M Millis C K Anonye M Reynolds |
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| Affiliation: | 1. Animal Physiology Laboratory, Department of Zoology, Graduate School of Arts and Sciences, College of Medicine, Howard University, Washington, D.C. 20059 USA;2. Department of Neurology, Graduate School of Arts and Sciences, College of Medicine, Howard University, Washington, D.C. 20059 USA;1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi''an, 710032, PR China;2. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, PR China;3. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310006, China;4. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Periodontology, College of Stomatology, Xi''an Jiaotong University, Xi''an, PR China;1. Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT;2. Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute at University of Utah, Salt Lake City, UT |
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| Abstract: | 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. |
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