In resting muscle, blood flow is regulated to meet the demand for O2 by the tissue. A modified ischemia (I)/reperfusion(R) investigation was systematically run and PISFO2, PaO2, Q and VO2 were observed. Twenty-nine spinotrapezius muscles from male Sprague-Dawley rats (284±20 grams) were surgically exteriorized for intravital microscopy to test a model relating blood flow, O2 supply and O2 demand. The model can aid in the understanding of the regulation of tissue PO2. The interstitial PO2 (PISFO2) and perivascular PO2 (PaO2) measurements were made using phosphorescence quenching microscopy (PQM). O2 consumption (VO2) values were obtained with a quasi-continuous, flash-synchronized, pressurized airbag to initiate ischemia and sample the rate of O¬2 change (dPO2/dt). Centerline red blood cell velocity was measured with an Optical Doppler Velocimeter and converted to flow using vessel diameter. 5-, 15-, 30-, 60-, 300- and 600-second ischemic durations were used to observe changes in PISFO2, Q, and VO2. A critical point was observed following 30 seconds of (I) where dPISFO2/dt during recovery was the fastest (4.25±0.72 mmHg/s) and was 1.00±0.16 mmHg/s following 600 seconds. Flow recovery, dQ/dt, peaked to 3.88±0.64 (µl•min-1)/s after 60 seconds of (I) but significantly dropped to 2.83±0.55 (µl•min-1)/s following 300 seconds of (I) but increased to 2.92±0.45 (µl•min-1)/s following 600 seconds. This gives evidence to a no-reflow phenomenon occurring in the extended periods of ischemia. A peak in VO¬2 to 309.2±45.0 nl O2/cm3•s with a time course of 160 seconds occurred following 600 seconds of ischemia. As the ischemic duration decreased, the time course and peak VO2 also decreased. VO2 following 300 seconds of (I) was significantly higher than 5-60 seconds of (I) (p <0.05) but was not significantly different from 600 seconds of (I). The information collected during the Q and VO2 studies can be incorporated into a factor, M, that relates VO2, Q and ∆PO2. M calculated for the recovery of 5- through 60-second (I) groups reasonably relates the three variables due to consistency and little variability. However, recovery in 600- and especially 300-second (I) groups showed higher variability in M which requires more consideration.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) is a condition in which peripheral skeletal muscle undergoes myopathic changes which impair muscle function, limit physical performance, and can lead to significant disability. While the etiology of the dysfunction is unknown, this study was conducted to test the hypothesis that chronic hypoxemia leads to alterations in oxygen transport and muscle function. A primary objective was to validate elastase-induced emphysema in rats as an animal model of skeletal muscle dysfunction in COPD.Arterial blood gases were used to determine the severity of hypoxemia and sodium dodecyl sulfate- polyacrylamide gel electrophoresis was used to determine the proportions of myosin heavy chain isoforms I, IIa, IIx, and IIb. Measures of microvascular oxygenation and blood flow in the spinotrapezius muscle allowed for determination of both convective and diffusive oxygen supply to the muscle, as well as calculation of muscle oxygen consumption at rest and during electrically stimulated three-minute muscle contractions. Muscle performance measures included peak force, force-time integral, and fatigue index. Due to a presumed rat respiratory virus, which likely resulted in the control group being nearly as hypoxemic as the elastase-induced emphysema group, this study was not able to definitively test the hypothesis that chronic hypoxemia leads to both a diminished supply and demand of oxygen in skeletal muscle. Although many of the results of the present study were not statistically significant, they exhibited consistent trends over time and are likely of physiological significance. All measures of muscle performance were lower in the emphysema group. In addition, spinotrapezius muscle oxygen consumption and blood flow were lower in the emphysema group. The addition of supplemental oxygen during isolated, small-muscle mass exercise did increase the force-time integral by ~18% in both groups, suggesting that muscle work in these hypoxemic animals may be limited by oxygen supply. Thus, the data on muscle fiber type, oxygen consumption and muscle performance suggest that elastase-induced emphysema in rats leads to a similar skeletal muscle dysfunction that is observed in humans with COPD, and indicates that it is a valid animal model of skeletal muscle dysfunction in COPD.