Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia assessed by contrast ultrasound

Abstract

. Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia assessed by contrast ultrasound. Am J Physiol Endocrinol Metab 282: E714-E720, 2002. First published November 13; 10.1152/ ajpendo.00373.2001.-The purpose of this study was to noninvasively quantify the effects of insulin on capillary blood volume (capBV) and RBC velocity (V RBC) in skeletal muscle in vivo with the use of contrast-enhanced ultrasound. We performed contrast ultrasound of the rat hindlimb adductor muscles at baseline and after 2-h infusions of either insulin (3 or 40 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or saline. Saline-treated animals were also studied during contractile exercise. V RBC and capBV were calculated from the relation between pulsing interval and video intensity. Femoral artery blood flow, measured by a flow probe, increased with both contractile exercise and insulin. Contractile exercise increased capBV more than twofold and V RBC fivefold. Insulin also increased capBV more than twofold in a dose-dependent fashion but did not significantly alter V RBC. Saline infusion did not significantly alter capBV, V RBC, or femoral artery blood flow. We conclude that physiological changes in skeletal muscle capillary perfusion can be assessed in vivo with the use of contrastenhanced ultrasound. Exercise increases both V RBC and capBV, whereas hyperinsulinemia selectively increases only capBV, which may enhance skeletal muscle glucose uptake. blood volume; capillaries; insulin THE NUMBER OF PERFUSED CAPILLARIES (N cap ) in skeletal muscle can change in response to various physiological stimuli. Increases in N cap during skeletal muscle exercise are thought to enhance capillary surface area for oxygen exchange and to decrease oxygen diffusion distance (4, 6, 7). Similarly, it has been proposed that insulin increases N cap , thereby enhancing glucose delivery to skeletal muscle by augmenting surface area for diffusion. Experimental evidence for insulin-mediated changes in microvascular perfusion in humans has been based largely on increases in limb blood flow and skeletal muscle blood volume that occur in response to hyperinsulinemia (1,3,12,14,17). The extent of capillary recruitment in skeletal muscle remains uncertain because previous studies have used techniques that provide a measure of total blood volume, most of which resides in larger conduit and resistance vessels (16). Hence, capillary responses to various physiological stimuli have been difficult to assess in intact skeletal muscle due to a paucity of noninvasive methods capable of quantifying capillary blood volume (capBV).Recently, changes in myocardial and renal capBV have been measured with the use of contrast-enhanced ultrasound imaging (2,22,23). This technique also provides information on microbubble velocity within capillaries by measuring their reappearance rate in tissue after their destruction with acoustic energy (2,22). Because the microvascular rheology of microbubbles is similar to that of red blood cells (8), this method can be used to study microvascular re...

Contrast-enhanced ultrasound measurement of microvascular perfusion relevant to nutrient and hormone delivery in skeletal muscle: A model study in vitro

“…Thus a four-fold increase in flow gave identical measures of microvascular volume. The implications of this are that when applied in vivo, the increase in microvascular volume (capillary recruitment) as has been reported for muscle contraction (Dawson et al, 2002) and for insulin action (Coggins et al, 2001;Rattigan et al, 1997) could not have been influenced by the accompanying increase in bulk flow. Independence has been assumed but not directly shown previously.…”

“…Impairments associated with vascular dysfunction can contribute to the metabolic syndrome and insulin resistance. Recently, using an ultrasound imaging technique, we reported that insulin action and muscle contraction each resulted in a marked increase in microvascular perfusion (capillary recruitment) of hind leg muscles of the rat (Dawson et al, 2002;Rattigan et al, 1997) and of human forearm (Coggins et al, 2001). We also observed that insulin's control of this process was impaired in insulin resistant states Wallis et al, 2002).…”

“…These studies can not be conducted in vivo and only one previous modeling study of this kind has been reported (Wei et al, 1998) where bulk flow was shown to correlate well with measured filling rate, but capillary volume was not determined. Accordingly, in the present study, CEU is used with constructed capillary tubing models in vitro to assess the effect of bulk flow and its potential for discriminating between different flow patterns within muscle that might explain capillary recruitment reported in vivo (Dawson et al, 2002;Rattigan et al, 1997;Vincent et al, 2006).…”

Skeletal Muscle Microvascular Recruitment by Physiological Hyperinsulinemia Precedes Increases in Total Blood Flow

“…Most recently, we have used ultrasound during albumin microbubble infusion to estimate microvascular volume (MV) in rat skeletal muscle in vivo (11). Using contrastenhanced ultrasound (CEU), we observed that exercise, a known stimulus for microvascular recruitment in muscle, enhanced MV.…”

“…To date, the best indicator that we have that 1-MX metabolism reflects microvascular perfusion comes from studies of the effect of electrical stimulation of muscle (11,17). We have shown that 1-MX metabolism increases in response to electrical stimulation (a known stimulus for capillary recruitment) in rat hindlimb both in vivo (11) and in a perfused preparation (17). In the perfused rat hindlimb preparation, total blood flow is held constant (17), yet 1-MX conversion to 1-MU is increased, suggesting that microvascular perfusion can be affected independently of total flow.…”