Hogan, Michael C., L. Bruce Gladden, Bruno Grassi, Creed M. Stary, and Michele Samaja. Bioenergetics of contracting skeletal muscle after partial reduction of blood flow. J. Appl. Physiol. 84(6): 1882-1888, 1998.-The purpose of this study was to examine the bioenergetics and regulation of O 2 uptake (V O 2 ) and force production in contracting muscle when blood flow was moderately reduced during a steadystate contractile period. Canine gastrocnemius muscle (n ϭ 5) was isolated, and 3-min stimulation periods of isometric, tetanic contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5 contractions/s (Hz) immediately followed by a reduction of blood flow [ischemic (I) condition] to 46 Ϯ 3% of the value obtained at 0.5 Hz with normal blood flow. The V O 2 of the contracting muscle was significantly (P Ͻ 0.05) reduced during the I condition [6.5 Ϯ 0.8 (SE) ml · 100 g Ϫ1 · min Ϫ1 ] compared with the same stimulation frequency with normal flow (11.2 Ϯ 1.5 ml · 100 g Ϫ1 · min Ϫ1 ), as was the tension-time index (79 Ϯ 12 vs. 123 Ϯ 22 N·g Ϫ1 · min Ϫ1 , respectively). The ratio of V O 2 to tension-time index remained constant throughout all contraction periods. Muscle phosphocreatine concentration, ATP concentration, and lactate efflux were not significantly different during the I condition compared with the 0.5-Hz condition with normal blood flow. However, at comparable rates of V O 2 and tension-time index, muscle phosphocreatine concentration and ATP concentration were significantly less during the I condition compared with normal-flow conditions. These results demonstrate that, in this highly oxidative muscle, the normal balance of O 2 supply to force output was maintained during moderate ischemia by downregulation of force production. In addition, 1) the minimal disruption in intracellular homeostasis after the initiation of ischemia was likely a result of steady-state metabolic conditions having already been activated, and 2) the difference in intracellular conditions at comparable rates of V O 2 and tension-time index between the normal flow and I condition may have been due to altered intracellular O 2 tension. oxygen uptake; exercise; adenosine 5Ј-triphosphate; lactate; lactic acid; mitochondrial respiration; phosphocreatine; glycolysis IN MOST CONDITIONS of steady-state muscle contractile activity, ATP production related to the O 2 uptake (V O 2 ) of the contracting muscle is tightly coupled to the rate of ATP demand so that steady-state energy expenditure is maintained with minimal change in intracellular ATP concentration ([ATP]; e.g., see Ref. 12). When the supply of O 2 (and oxidative substrate) to the mitochondria is sufficient, increases in myofibril ATPase activity with higher energy demands result in changes in the concentration of several signals [phosphocreatine (PCr), ADP, P i , etc.] that are thought to regulate mitochondrial respiration (4,5,18,20,22) in a manner that causes oxidative phosphorylation to increase proportionally with ATPase activity. However, when the supply of O 2 to ...