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Biomedical subjects

M A Vincent

Publications and source records attributed to M A Vincent.

17 recordsLinked to original sources
PubMed2003

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin.

We examined the effects of inhibiting nitric oxide synthase with Nomega-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU.min-1.kg-1) significantly increased hindlimb total blood flow (0.69 +/- 0.02 to 1.22 +/- 0.11 ml/min, P < 0.05), glucose uptake (0.27 +/- 0.05 to 0.95 +/- 0.08 micromol/min, P < 0.05), 1-MX uptake (5.0 +/- 0.5 to 8.5 +/- 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 +/- 1.6 to 15.0 +/- 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% (P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.

Animals↗
PubMed2002

Skeletal muscle microvascular recruitment by physiological hyperinsulinemia precedes increases in total blood flow.

Supraphysiological doses of insulin enhance total limb blood flow and recruit capillaries in skeletal muscle. Whether these processes change in response to physiological hyperinsulinemia is uncertain. To examine this, we infused either saline (n = 6) or insulin (euglycemic clamp, 3.0 mU x min(-1) x kg(-1), n = 9) into anesthetized rats for 120 min. Femoral artery flow was monitored continuously using a Doppler flow probe, and muscle microvascular recruitment was assessed by metabolism of infused 1-methylxanthine (1-MX) and by contrast-enhanced ultrasound (CEU). Insulin infusion raised plasma insulin concentrations by approximately 10-fold. Compared with saline, physiological hyperinsulinemia increased femoral artery flow (1.02 +/- 0.10 vs. 0.68 +/- 0.09 ml/min; P < 0.05), microvascular recruitment (measured by 1-MX metabolism [6.6 +/- 0.5 vs. 4.5 +/- 0.48 nmol/min; P < 0.05] as well as by CEU [167.0 +/- 39.8 vs. 28.2 +/- 13.8%; P < 0.01]), and microvascular flow velocity (beta, 0.14 +/- 0.02 vs. 0.09 +/- 0.02 s(-1)). Subsequently, we studied the time dependency of insulin's vascular action in a second group (n = 5) of animals. Using CEU, microvascular volume was measured at 0, 30, and 90 min of insulin infusion. Insulin augmented microvascular perfusion within 30 min (52.8 +/- 14.8%), and this persisted at 90 min (64.6 +/- 9.9%). Microvascular recruitment occurred without changes to femoral artery flow or beta. We conclude that insulin increases tissue perfusion by recruiting microvascular beds, and at physiological concentrations this precedes increases in total muscle blood flow by 60-90 min.

Animals↗
PubMed2001

Spatial distribution of nutritive and nonnutritive vascular routes in perfused rat hindlimb muscle using microspheres.

Skeletal muscle appears to have two vascular flow routes, nutritive and nonnutritive, where the balance of flow is controlled by vasoconstrictors. In the present study, spatial distributions of the two flow routes in muscles of the perfused rat hindlimb were attempted using fluorescent microspheres (15 microm in diameter). Microspheres were injected during steady-state perfusion with norepinephrine (proposed recruiter of nutritive flow), serotonin (proposed recruiter of nonnutritive flow), or vehicle. The three-dimensional location of individual microspheres in representative muscles was determined using a Fluorescent Imaging CryoMicrotome. Norepinephrine and serotonin each increased perfusion pressure (P < 0.05) but stimulated and inhibited oxygen consumption (P < 0.05), respectively. The distribution of microspheres lodged in muscle was independent of the agent used. Spatial perfusion indices for norepinephrine, serotonin, and vehicle did not differ from each other. Similarly, there was no difference in these indices for a theoretical distribution where microspheres were deliberately positioned in muscle bundle capillaries or interfibrillar connective tissue vessels. We conclude that the nutritive and nonnutritive flow routes are distributed throughout muscle sections consistent with their locations in muscle bundle capillaries and interfibrillar connective tissue, respectively.

Animals↗
PubMed2001

Size-dependent effects of microspheres on vasoconstrictor-mediated change in oxygen uptake by perfused rat hindlimb.

There are two vascular flow routes in skeletal muscle that can be accessed by different vasoconstrictors acting at selective sites in the vascular tree. Thus, angiotensin II (AII) and serotonin (5-HT), which stimulate and inhibit metabolism, do so by directing flow to nutritive and nonnutritive routes, respectively. In the present study the association between vascular flow route recruitment and metabolism was assessed by embolism with microspheres of different sizes. Latex microspheres (MS) of four sizes, 5.4 (MS5), 11.8 (MS12), 23.4 (MS23), and 93.6 microm (MS94), were injected during AII- or 5-HT-mediated constriction or under basal conditions and the effects on hindlimb oxygen uptake (VO2), perfusion pressure, and venous flow rate were determined. MS5 or MS12 partially reversed 5-HT-mediated inhibition of VO2 by 39 and 55%, respectively (P < 0.05), fully reversed AII-mediated stimulation of VO2 (P < 0.05), stimulated basal VO2 (P < 0.05), and increased pressure while only marginally (<10%) decreasing venous flow. MS23 or MS94 dose-dependently increased pressure and inhibited VO2, during basal or 5HT- and AII-mediated constriction, while only marginally decreasing venous flow. In conclusion, microspheres of less than 12 microm when injected into the constant flow perfused rat hindlimb can alter metabolism by altering flow distribution between nutritive and nonnutritive routes. Larger MS (> or =24 microm) are nondiscriminating possibly because they exceed the size of vessels in which branch points to the two vascular routes are located. Overall the findings provide further evidence for two microvascular routes in muscle, one nutritive and the other nonnutritive.

Angiotensin II↗
PubMed2000

Functional and desensitizing effects of the novel synthetic vanilloid-like agent 12-phenylacetate 13-acetate 20-homovanillate (PPAHV) in the perfused rat hindlimb.

1. In the present study, the effects of the novel vanilloid agonist, 12-phenylacetate 13-acetate 20-homovanillate (PPAHV), on oxygen consumption (VO(2)) and vascular resistance (perfusion pressure, PP) were investigated in the constant flow, perfused rat hindlimb. The acute desensitizing properties of this novel synthetic agent were also examined. 2. Maximum stimulation of VO(2) was produced by 0.2 microM PPAHV (delta VO(2), 0.83+/-0.06 micromol g(-1) h(-1)) and was accompanied by mild vasoconstriction (increase in PP; 8.0+/-1.1 mmHg). The highest concentration of PPAHV tested (2 microM) caused inhibition of VO(2) (delta VO(2), -2.73+/-0.51 micromol g(-1) h(-1)) and strong vasoconstriction (delta PP, 42.0+/-1.2 mmHg). 3. Capsazepine (10 microM) caused a parallel shift to the right of both VO(2) and PP concentration-response curves for PPAHV (pK(b)=5.00), indicative of competitive binding to vanilloid receptors. 4. The stimulation of VO(2) produced by 0.2 microM PPAHV decreased, but was not completely abolished, after repeated infusion of PPAHV (change in VO(2), first infusion, 0.66+/-0.18 micromol g(-1) h(-1); sixth infusion, 0.29+/-0. 08 micromol g(-1) h(-1), P<0.05), an acute tachyphylactic response not previously seen with the repeated infusion of other vanilloid analogues. Conversely, the PP response to repeated PPAHV infusion increased (delta PP, first infusion, 5.8+/-0.7 mmHg; sixth infusion, 9.0+/-0.6 mmHg, P<0.05). 5. In conclusion, PPAHV produces vasoconstriction and a biphasic effect on VO(2) in the perfused rat hindlimb very similar to that induced by naturally occurring vanilloids. Both effects are blocked by the competitive antagonist capsazepine. Since, the metabolic response to low concentrations of PPAHV (stimulation of VO(2)) undergoes tachyphylaxis, the present data suggest that PPAHV desensitizes putative vanilloid receptors in the hindlimb.

Animals↗
PubMed2000

Nutritive and non-nutritive blood flow: rest and exercise.

There is growing evidence to support the notion of two vascular routes within, or closely associated with skeletal muscle. One route is in intimate contact with muscle cells (hence is known as 'nutritive') and the other functions as a vascular shunt (and has had the interesting misnomer of 'non-nutritive'). Recent findings suggest that the 'non-nutritive' route may, in part, be those vessels in closely associated (interlacing?) connective tissue that nourishes attached fat cells, and may form the basis of 'marbling' of muscle in obesity. In addition, embolism studies using various size microspheres indicate that the 'non-nutritive' vessels are likely to be capillaries fed by terminal arterioles that branch from the same transverse arterioles as those supplying terminal arterioles of the muscle capillaries (i.e. two vascular systems operating in parallel). The proportion of flow distributed between the two routes is tightly regulated and controls muscle metabolism and contraction by regulating hormone and substrate delivery as well as product removal. Because a high proportion of nutritive flow may elevate the set point for basal metabolism, a low proportion of nutritive flow in muscle at rest confers an evolutionary advantage, particularly when food is scarce. In addition, the proportion of flow that is carried by the non-nutritive routes at rest affords a flow reserve that can be switched to the nutritive route to amplify nutrient supply during exercise. Alternatively the non-nutritive route may allow flow to escape when active muscle contraction compresses its nutritive capillaries. Thus rhythmic oscillation of blood flow between the non-nutritive and nutritive networks may aid the muscle pump.

Animals↗
PubMed1999

Factorial validity of the Bulimia Test-Revised in adolescent boys and girls.

The present study examined the psychometric properties and principal components structure of the Bulimia Test Revised (BULIT-R; [Thelen, M.H., Farmer, J., Wonderlich, S. & Smith, M. (1991). A revision of the Bulimia Test: the BULIT-R. Psychological Assessment, 3, 119-124.]) using a sample of early adolescent males and females. Three hundred and six girls (mean age = 13.66; S.D. = 1.12) and 297 boys (mean age = 13.89: S.D. = 1.13) from grades 7-10 completed the BULIT-R as part of a larger study investigating disordered eating in early adolescence. In comparison to the 5 factors identified in adult female samples, the factor analysis identified four similar factors for adolescent boys and girls: bingeing, control, normative weight loss (dieting and exercise) and extreme weight loss behaviors (vomiting, diuretics and laxatives). The findings highlight similarities between boys and girls and differences in the factorial nature of the BULIT-R for adult and adolescent samples. The BULIT-R also demonstrated good reliability with adolescent samples and adequate concurrent validity with the DFT, DEBQ and binge eating as defined by the DSM-IV criteria. The emergence of bingeing and control as two distinct factors is an important distinction that needs to be considered when attempting to provide accurate incidence rates of binge eating and bulimic symptomatology in adolescents.

Adolescent↗
PubMed1999

Increased metabolism of infused 1-methylxanthine by working muscle.

Exogenous substrates for capillary endothelial enzymes have potential as markers for changes in capillary recruitment (albeit nutritive flow). The metabolism of infused 1-methylxanthine (1-MX) to 1-methylurate (1-MU) by capillary endothelial xanthine oxidase of the constant-flow perfused rat hindlimb was shown previously to decrease with oxygen uptake (VO2) when nutritive flow was decreased. In the present study, the metabolism of 1-MX was investigated under conditions when VO2 and nutritive flow are known to increase during muscle contraction. The constant-flow red blood cell-perfused rat hindlimb at 37 degrees C was used with sciatic nerve stimulation, and perfusate samples from whole hindlimb and working muscles taken for analysis of oxygen, lactate, 1-MX and 1-MU. Flow to muscle was assessed separately using fluorescent microspheres and was found to increase 2.3-fold to the working muscles while flow to the non-working leg muscles decreased to compensate. The activity of xanthine oxidase of whole muscle extracts was not altered by contraction. Samples from the vein draining the working muscles, and microsphere measurements of flow, indicated increased VO2 (5.5-fold to 249.2 +/- 43.1 micromol h-1 g-1, P < 0.001), and 1-MX conversion (2.5-fold to 1.87 +/- 0.25 micromol h-1 g-1, P < 0.01) (SEM are shown). It is concluded that as 1-MX metabolism parallels VO2, this substrate may be a useful indicator of changes in capillary (nutritive) surface area in muscle.

Algorithms↗
PubMed1998

Microsphere infusion reverses vasoconstrictor-mediated change in hindlimb oxygen uptake and energy status.

The vasoconstrictors, angiotensin II (AII) and serotonin (5-HT) produce opposing metabolic effects and appear to control different flow routes in the constant-flow perfused rat hindlimb. In the present study the association between vascular flow route recruitment and metabolism was assessed by selective microsphere embolism of either route. Microspheres (MS, 11.9 +/- 0.1 microns, mean +/- SE diameter) were injected during AII, 5-HT or vehicle infusions (basal conditions) and the effects on hindlimb (4.7 +/- 0.1 g muscle) oxygen uptake (VO2) and indices of energy status CrP/Cr, CrP/ATP and energy charge (EC) of the calf muscle group assessed. MS (1.5 x 10(6)) injected during vehicle, or 5-HT infusion increased VO2 (P < 0.05) but did not affect energy status. During AII, MS decreased VO2. Change in VO2 correlated positively with CrP/Cr (r = 0.68, P < 0.0001) and CrP/ATP (r = 0.51, P < 0.001) but not EC (r = 0.08, P = 0.59). MS (1.5 x 10(6)) increased pressure but did not affect the flow rate. The metabolic changes resulting from 1.5 x 10(6) microspheres were intensified by a second injection of 1.5 x 10(6) microspheres but further injection (> 3.0 x 10(6) microspheres) began to inhibit flow. It is concluded that a finite number (< or = 3.0 x 10(6)) of microspheres of 11.9 microns diameter has opposite effects on VO2 depending on the vasoconstrictor present and that these effects result from the occlusion of the different vascular route accessed by each vasoconstrictor. The data support the proposal that hindlimb metabolism can be controlled by vasoconstrictors as a result of selective vascular recruitment.

Angiotensin II↗
PubMedDate not supplied

[Nephretic colic in patients with arrhythmia (author's transl)].

The authors relate one case of obstruction by emboly in the renal artery. The diagnosis were too late for conservative surgery. In this case, they insist on the particulary signs of that nephretic colic and they show the diagnosis measures which are able to permit a conservative surgery in urgency.

Colic↗