. Muscle capillary blood flow kinetics estimated from pulmonary O2 uptake and near-infrared spectroscopy. J Appl Physiol 98: 1820 -1828, 2005. First published January 7, 2005 doi:10.1152/japplphysiol.00907.2004.-The near-infrared spectroscopy (NIRS) signal (deoxyhemoglobin concentration; [HHb]) reflects the dynamic balance between muscle capillary blood flow (Q cap) and muscle O2 uptake (V O2m) in the microcirculation. The purposes of the present study were to estimate the time course of Q cap from the kinetics of the primary component of pulmonary O2 uptake (V O2p) and [HHb] . However, there was no significant difference between MRT of Q cap and P-V O2 for both intensities (P ϭ 0.99), and these parameters were significantly correlated (M and H; r ϭ 0.99; P Ͻ 0.001). In conclusion, we have proposed a new method to noninvasively approximate Q cap kinetics in humans during exercise. The resulting overall Q cap kinetics appeared to be tightly coupled to the temporal profile of V O2m. exercise; skeletal muscle; oxygenation INSIGHTS ON THE CONTROL OF exercising muscle blood flow (Q m ) can be gained from the investigation of its response in the transitional phase (i.e., kinetics) (21, 27), but because of methodological constraints the kinetics of Q m in humans have been studied primarily in larger vessels (1,16,22,31,37,42,44).The difficulty in obtaining measurements with a time resolution that allows reliable kinetic analysis during large muscle mass exercise (e.g., cycling or running) has led to a predominant use of knee extensor or forearm exercise with measurements of blood flow made by Doppler ultrasound (11,22,31,37,42,44). These investigations have shown that the Q m response is biphasic with an initial fast phase determined by the combined effects of muscle contraction (muscle pump) (41) and possibly rapid vasodilation (48) followed by a second slower phase that appears to match O 2 delivery and utilization (43).Several studies have addressed the relationship between Q m and muscle O 2 uptake (V O 2m ) kinetic response after the onset of exercise (5,12,14,16,22,31 (27). To date, for technical and ethical reasons, assessing the kinetics of muscle capillary blood flow (Q cap ) in humans has been problematic. Resolution of this discrepancy in Q m kinetics relative to those of V O 2m is crucial to advancing our understanding of the mechanisms that govern the control of both Q m and V O 2m in health and disease.Near-infrared spectroscopy (NIRS) provides a noninvasive measure of muscle oxygenation (or O 2 extraction) in the microcirculation. Although distinction between hemoglobin (Hb) and myoglobin (Mb) with regard to absorption of the near-infrared light cannot be made, the deoxygenated Hb/Mb (deoxy-Hb/Mb) signal obtained by NIRS has been used as an index of local O 2 extraction reflecting the V O 2m -to-Q m ratio in the capillaries (9, 15). The time course of deoxy-Hb/Mb after the onset of exercise resembles qualitatively and quantitatively the arteriovenous O 2 difference [(a-v)O 2 ] observed in separate...

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were significantly (P < 0.05) different from each other. We conclude that for moderate intensity knee extension exercise, conduit artery blood flow (Q FA ) kinetics may not be a reasonable approximation of blood flow kinetics in the microcirculation (Q cap ), the site of gas exchange. This temporal dissociation suggests that blood flow may be controlled differently at the conduit artery level than in the microcirculation.

To test for evidence of a muscle pump effect during steady-state upright submaximal knee extension exercise, seven male subjects performed seven discontinuous, incremental exercise stages (3 min/stage) at 40 contractions/min, at work rates ranging to 60-75% peak aerobic work rate. Cardiac cycle-averaged muscle blood flow (MBF) responses and contraction-averaged blood flow responses were calculated from continuous Doppler sonography of the femoral artery. Net contribution of the muscle pump was estimated by the difference between mean exercise blood flow (MBFM) and early recovery blood flow (MBFR). MBFM rose in proportion with increases in power output with no significant difference between the two methods of calculating MBF. For stages 1 and 5, MBFM was greater than MBFR; for all others, MBFM was similar to MBFR. For the lighter work rates (stages 1-4), there was no significant difference between exercise and early recovery mean arterial pressure (MAP). During stages 5-7, MAP was significantly higher during exercise and fell significantly early in recovery. From these results we conclude that 1) at the lightest work rate, the muscle pump had a net positive effect on MBFM, 2) during steady-state moderate exercise (stages 2-4) the net effect of rhythmic muscle contraction was neutral (i.e., the impedance due to muscle contraction was exactly offset by the potential enhancement during relaxation), and 3) at the three higher work rates tested (stages 5-7), any enhancement to flow during relaxation was insufficient to fully compensate for the contraction-induced impedance to muscle perfusion. This necessitated a higher MAP to achieve the MBFM.

An increase in muscle contraction frequency could limit muscle blood flow QM compromising the matching of QM and muscle oxygen uptake VO2M. This study examined the effects of pedal cadence on skeletal muscle oxygenation at low, moderate and peak exercise. Nine healthy subjects [24.7+/-6.3 years (SD)] performed incremental cycling exercise at 60 and 100 rpm. Pulmonary VO2(VO2P) was measured breath-by-breath and vastus lateralis oxygenation was determined by near-infrared spectroscopy (NIRS). The deoxyhemoglobin signal ([HHb]) from NIRS was used to estimate microvascular O2 extraction (i.e., [HHb] proportional, variant VO2M/QM). The VO2P and [HHb] for low, moderate and at peak exercise were determined. The VO2P at 60 rpm (low=0.64+/-0.13, moderate=2.03+/-0.38 and peak=3.39+/-0.84 l/min) were lower (P<0.01) than at 100 rpm (1.29+/-0.23, 2.14+/-0.39 and 3.54+/-0.88 l/min, respectively). There was a progressive increase in [HHb] from low to peak exercise. However, there was no significant difference (ANOVA, P=0.94) for the 60 (in microM, low=24.0+/-9.5, moderate=30.5+/-13.8 and peak=36.7+/-16.5) and 100 contractions/min (in microM, low=25.7+/-11.6, moderate=32.1+/-14.0 and peak=35.4+/-16.5). We conclude that vastus lateralis O2 extraction was similar at 60 and 100 cpm, suggesting that the VO2M/QM in the microcirculation was not altered and, presumably, no impairment of QM occurred with the increase in pedal frequency.

The kinetic characteristics of muscle capillary blood flow (Q cap ) during recovery from exercise are controversial (e.g. one versus two phases). Furthermore, it is not clear how the overallQ cap kinetics are temporally associated with muscle oxygen uptake (V O 2 m ) kinetics. To address these issues, we examined the kinetics ofQ cap estimated from the rearrangement of the Fick equation

During post-occlusive reactive hyperemia (PORH) there is a temporary increase in the total hemoglobin + myoglobin (T[Hb+Mb]) signal as measured by near-infrared spectroscopy (NIRS). This transient increase predicts differences in the kinetic responses of deoxy[Hb+Mb] and oxy[Hb+Mb] during PORH. The purpose of this study was to determine whether sigmoidal (Gompertz or logistic) or exponential functions better describe these response curves during PORH. The fit of the three functions (exponential, Gompertz and logistic) to the NIRS responses, as determined from residual sum of squares, was compared using repeated measures ANOVA on Ranks. The Gompertz function provided a better fit to the oxy[Hb+Mb] response curve than did either the exponential or logistic function (χ (2) = 21.7, df = 2, p < 0.001). The logistic function provided a better fit for the deoxy[Hb+Mb] response (χ (2) = 22.9, df = 2, p < 0.001) than did either the Gompertz or exponential functions. For both NIRS signals, the better fitting sigmoidal functions fit the data well, with an average r value of 0.99 or greater. Adipose tissue thickness was correlated with parameters related to signal strength (amplitude, r = 0.86-0.89; baseline, r = 0.67-0.75; all p < 0.001) but was not related to kinetic parameters (time constant and inflection point; p > 0.05 for all comparisons). These results suggest that during PORH distinct sigmoidal mathematical functions best describe the responses of the oxy[Hb+Mb] (Gompertz) and deoxy[Hb+Mb] (logistic) as measured by NIRS. Further, differences in both the kinetic and amplitude aspects for the responses of oxy[Hb+Mb] and deoxy[Hb+Mb] predict the observed transient change in T[Hb+Mb]. Our methods provide a technique to evaluate and quantify NIRS responses during PORH, which may have clinical utility.

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