title: Relationship between intracellular oxygenation and neuromuscular conduction during hypoxic hypoxia.
abstract: Previous studies have shown that high-altitude hypoxic hypoxia is associated with reduced ventilatory capacity that may be related to skeletal muscle weakness. In the present investigation, ascent to high altitude (4,000 m) was simulated experimentally by exposure of male rats (Sprague-Dawley, 250-350 g), anesthetized with thiopental sodium (25 mg/kg, i.p.), to a breathing gas mixture of 12% oxygen diluted in 88% nitrogen (FiO2 = 0.12). Determinations of oxygen saturation on microsamples (250 ul) of arterial and central venous blood were made spectrophotometrically. Neuromuscular conduction latency was measured following electrostimulation of the sciatic nerve (1-5 V, 0.5 msec duration, 1-40 Hz) and recording of the electromyogram from the gastrocnemius muscle. Experimental hypoxia (FiO2 = 0.12) produced a highly significant increase in conduction latency from a control value (mean +/- SEM) of 3.06 +/- 0.16 msec to 4.02 +/- 0.31 msec (n = 10, P less than 0.001). Conduction latency increased with decreasing arterial oxygen saturation from a control value of 92.9% +/- 0.18% to 83.2% +/- 0.76% (P less than 0.001) in the absence of statistically significant changes in central venous oxygen saturation, central venous pressure, arterial and central venous pH, and heart rate. A significant decrement in the mean arterial blood pressure from a control value of 85 +/- 1.5 mm Hg to 69 +/- 1.5 mm Hg suggests that local ischemia may be a component of this model. These responses were accompanied by marked reduction in uptake of 3,3'-diaminobenzidine (DAB) by gastrocnemius muscle mitochondria, suggesting decreased intracellular activity of cytochrome oxidase. It was concluded that exposure of rodents to hypoxic gas mixtures may provide a suitable model for studying the mechanism of skeletal muscle weakness associated with ascent to high altitude and of other conditions wherein the supply of oxygen to tissues is limited.
mesh_terms: D015100:3,3'-Diaminobenzidine / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002496:Central Venous Pressure; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission
chemical_list: D010108:Oxyhemoglobins; D015100:3,3'-Diaminobenzidine; D010100:Oxygen