Role of O₂ in regulating tissue respiration in dog muscle working in situ

This study was designed to investigate the role of tissue oxygenation in some of the factors that are thought to regulate muscle respiration and metabolism. Tissue oxygenation was altered by reductions in O₂ delivery (muscle blood flow x arterial O₂ content), induced by decreases in arterial PO₂ (Pa(O₂)). O₂ uptake (V̇O₂) was measured in isolated in situ canine gastrocnemius at rest and while working at two stimulation intensities (isometric tetanic contractions at 0.5 and 1 contractions/s) on three separate occasions, with only the level of Pa(O₂) (78, 30, and 21 Torr) being different for each occasion. Muscle blood flow was held constant (pump perfusion) at each work intensity for the three different levels of Pa(O₂). Muscle biopsies were obtained at the end of each rest and work period. Muscle V̇O₂ was significantly less (P < 0.05) at both stimulation intensities for the hypoxemic conditions, whereas [ATP] was reduced only during the highest work intensity during both hypoxemic conditions (31% reduction at 21 Torr Pa(O₂) and 17% at 30 Torr). For each level of Pa(O₂), the relationships between the changes that occurred in V̇O₂ and levels of phosphocreatine, ADP, and ATP/ADP · P(i) as the stimulation intensity was increased were significantly correlated; however, the slopes and intercepts of these lines were significantly different for each Pa(O₂). Thus a greater change in any of the proposed regulators of tissue respiration (e.g., phosphocreatine, ADP) was required to achieve a given V̇O₂ as Pa(O₂) was decreased. These results indicate that V̇O₂ can be dissociated from these proposed regulators of tissue respiration and that this is likely due to an interaction with tissue or mitochondrial O₂ tension, thereby demonstrating the importance of O₂ as a modulator of the regulators of tissue respiration.