Jack K. Barclay

Blood flow and pressure relationships which determine VO2max

The role of O2 delivery in regulating VO2max has been studied in an isolated gastrocnemius-plantaris muscle preparation contracting in situ; recent data addressing this issue are presented. VO2 increases nonlinearly with stimulation frequency reaching a peak at 5 twitches.s-1 or 1 tet.s-1 (200 ms trains, 50 imp.s-1). Further increases in stimulation frequency result in a lower VO2. Measured VO2 maxima are less than predicted VO2 capacity, and peak VO2 during tetanic contractions is greater than that during twitches. Above 150 imp.min-1, VO2 is directly related to the level of blood flow attained as VO2/Q (arterial-venous O2 difference) is fixed by some unknown mechanism. Increasing blood flow, with a pump, during 1.s-1 tetanic contractions increases O2 diffusive conductance and peak VO2. When O2 delivery is reduced, ischemic hypoxia appears to result in more rapid reductions in muscle performance than hypoxic hypoxia because of decreases in perfusion pressure and Q. 31P-NMR studies reveal that reductions in creatine phosphate and energy charge are similar between ischemia and hypoxia suggesting a common regulator, O2. We conclude that VO2max is limited by O2 delivery as a result of a limited and uneven distribution of muscle blood flow. These limitations appear secondary to mechanical restraints imposed by contraction duty cycle and vascular compression.

Metabolic factors from exercising muscle and the proliferation of endothelial cells.

In order to identify factors that may be involved in angiogenesis in mammalian skeletal muscle after endurance exercise, the growth of cultured vascular endothelial cells derived from the canine hindlimb was measured in response to hypoxia and changes in temperature and concentrations of hydrogen ion and adenosine. Endothelial cells were freed from vessels of exsanguinated canine hindlimbs using collagenase. Cultures were grown on plastic culture dishes at 37 degrees C and 40 torr CO2 in air. Primary cultures reached confluency by 21 days. Cell number in secondary cultures was significantly increased in 7 days by exposure to 35 torr oxygen for 1 h daily, but cell growth rate was unaffected by 65 torr oxygen. Cell growth was inhibited when hydrogen ion concentration was increased by adding lactic acid daily (5 mmol X l-1). Exposing cell cultures for 1 h daily to an elevated PCO2 (70 torr) or to an environmental temperature of 41 degrees C, adding sodium lactate (5 mmol X l-1), or adenosine (10 or 100 mumol X l-1) daily did not affect cell growth rate. Thus, hypoxia increased the growth rate of cultured vascular endothelial cells and may play a role in blood vessel growth in vivo.

Polycythemia decreases fatigue in tetanic contractions of canine skeletal muscle.

PURPOSE The effects of an acute polycythemia on muscle fatigue development were investigated in the self-perfused canine gastrocnemius in situ. METHODS Following isolation of the gastrocnemius, dogs (N = 5) were made polycythemic through a bolus injection of packed erythrocytes (hematocrit (Hct) = 90-92%) to raise systemic Hct to 63.5 +/- 0.5%. Subsequently, the gastrocnemius was stimulated, through the sciatic nerve, to perform 20 min of isotonic tetanic contractions (60 x min(-1), 200 ms, 50Hz). Control (normocythemic) animals (N = 5) underwent an identical contraction regimen. RESULTS Although blood flow to the gastrocnemius was not different at any time, oxygen delivery was significantly increased during polycythemia (peak = 33.7 +/- 2.2 mL x 100 g(-1) x min-1) over control (peak = 25.1 +/- 2.1 mL x 100 g(-1)x min(-1)) at all times during contraction. Oxygen uptake by the gastrocnemius, although consistently increased, was not significantly different between the normocythemic and polycythemic conditions at any time. The rate of fatigue was significantly decreased over the first 6 min of contraction in polycythemic animals (3.5 +/- 0.6% x min(-1)) when compared with controls (5.8 +/- 0.7% x min(-1)). Subsequent fatigue development was not different between groups. As a result of the early rate differences in fatigue, however, the work production in polycythemic animals was significantly greater than in normocythemic dogs for the duration of the contraction period. CONCLUSION We conclude that during high metabolic rate isotonic tetanic contractions, muscle fatigue development is diminished by polycythemia, but the ergogenic effect appears to be transient.