Impaired Nutritive Skeletal Muscle Blood Flow in Patients with Chronic Renal Failure

1990 ◽  
Vol 79 (3) ◽  
pp. 239-245 ◽  
Author(s):  
John R. Bradley ◽  
Janice R. Anderson ◽  
David B. Evans ◽  
Alan J. Cowley

1. The possibility that abnormalities of skeletal muscle may limit the exercise tolerance of patients with chronic renal failure was investigated in patients undergoing regular haemodialysis. 2. Blood flow to the calf, a vascular bed consisting predominantly of skeletal muscle, was measured in six patients before and after exercise and compared with values obtained from 12 control subjects. 3. The patients were limited on exertion and had an abnormal response of calf blood flow to bicycle exercise. Resting calf blood flow was similar in patients and control subjects, but the mean increase in calf blood flow in response to submaximal exercise was 0.55 (sem 0.12) ml min−-1 100 ml−-1 in the patients and 1.43 (sem 0.17) ml min−-1 100 ml−-1 in the control subjects. The increase after symptom-limited maximal exercise was 1.50 (sem 0.80) ml min−-1 100 ml−-1 in the patients and 4.20 (sem 0.40) ml min−-1 100 ml−-1 in the control subjects. 4. Skeletal muscle biopsies from eight haemodialysis patients were studied by histochemistry and electron microscopy. 5. Oxidative enzyme activity was increased and there were large subsarcolemmal aggregates of structurally normal mitochondria. Necrotic capillaries were observed as empty basement membrane tubes containing fragments of degenerating endothelium. 6. The changes were compatible with a response to a chronic reduction in skeletal muscle blood flow.

2000 ◽  
Vol 99 (5) ◽  
pp. 383-392 ◽  
Author(s):  
R. Andrew P. SKYRME-JONES ◽  
Richard C. O'BRIEN ◽  
Ian T. MEREDITH

We and others have previously documented increased resting and exercise-induced skeletal muscle blood flow in young subjects with Type I (insulin-dependent) diabetes mellitus compared with healthy controls. Both NO and prostanoids are important regulators of vascular tone and may therefore contribute to this hyperaemia. The aim of the present study was to determine the contribution of NO and vasodilator prostanoids to this skeletal muscle hyperaemia in diabetes. We assessed the effects of infusion into the intrabrachial artery of the cyclo-oxygenase inhibitor acetylsalicylic acid (ASA; aspirin) and of the L-arginine analogue NG-monomethyl-L-arginine (L-NMMA) on skeletal muscle blood flow in subjects with Type I diabetes mellitus (DM subjects) and control subjects. Blood flow was measured by venous occlusion plethysmography. Isotonic forearm exercise involved 2 min of wrist flexion and extension. Resting flow (forearm blood flow; FBF) was augmented in DM subjects, as was peak exercise-related blood flow (PFBF) and the volume repaid to the forearm 5 min after exercise (AUC 5, where AUC is area under the flow–time curve) (P < 0.05), even when accounting for differences in basal flow. Infusion of L-NMMA reduced resting flow by 48% in controls (P < 0.005) and by 12% in DM subjects (not significant). L-NMMA reduced PFBF and AUC 5 by 29% (P < 0.05) and 39% (P < 0.0005) respectively in controls, but had no significant effect on these parameters in DM subjects. Infusion of ASA reduced FBF, PFBF and AUC 5 in both DM (P < 0.05) and control (P < 0.05) subjects, but the magnitude of this reduction was greater in DM than in control subjects (ANOVA, P < 0.05), even when differences in resting FBF were accounted for. Indeed, ASA eliminated the differences in FBF, PFBF and AUC 5 between DM and control subjects. Thus increased release of vasodilator prostanoids, rather than of NO, appears to account for skeletal muscle hyperaemia in Type I diabetes.


2000 ◽  
Vol 278 (1) ◽  
pp. H239-H248 ◽  
Author(s):  
Søren Galatius ◽  
Henrik Wroblewski ◽  
Vibeke B. Sørensen ◽  
Peter Bie ◽  
Henrik Arendrup ◽  
...  

In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief head-up tilt that appears to normalize after transplantation (HTX) may be present during prolonged observation also. Therefore, we studied the effect of prolonged (30 min) 50° head-up tilt on calf skeletal muscle blood flow measured by the local133Xe washout method in CHF and after HTX and in patients with the presence vs. absence of native right atrium (+PNA and −PNA, respectively). During brief head-up tilt, skeletal muscle blood flow increased 13 ± 42% in 9 severe CHF patients in contrast to a −28 ± 22% decrease ( P < 0.01) in 11 control subjects, −24 ± 30% decrease in 15 moderate CHF patients ( P < 0.05), −25 ± 14% decrease in 12 patients with recent HTX ( P < 0.01), and −21 ± 24% decrease in 8 patients with distant HTX ( P = 0.06). However, during sustained tilt, blood flow declined to similar levels of that in the other groups in severe CHF. HTX −PNA vs. +PNA showed blunted skeletal muscle vasomotor control ( P < 0.05) and a higher systolic blood pressure (139 ± 14 vs. 125 ± 15 mmHg, P < 0.05) and heart rate (92 ± 10 vs. 83 ± 8 beats/min, P < 0.05). Thus paradox vasodilatation of calf skeletal muscle in severe CHF is present only during brief but not prolonged tilt. This may be one explanation of the rare presence of orthostatic intolerance in CHF and implies only a minor possible role for the abnormality in edema pathogenesis. Removal of all right atrium in HTX has an important hemodynamic impact that may possibly affect later clinical outcome.


1997 ◽  
Vol 273 (1) ◽  
pp. H405-H410 ◽  
Author(s):  
R. C. Hickner ◽  
J. S. Fisher ◽  
A. A. Ehsani ◽  
W. M. Kohrt

The role of nitric oxide at rest and in the active hyperemic response within skeletal muscle was investigated in eight physically active men. Three microdialysis probes were inserted into the vastus lateralis of the quadriceps femoris muscle group in each subject. Microdialysis probes were perfused with a Ringer solution containing 5.0 mM ethanol, 2.5 mM glucose, and either 10 mg/ml of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) monoacetate salt, 30 mg/ml of the nitric oxide precursor L-arginine, or no additional substance (control probe). Subjects performed one-legged cycling exercise at work rates ranging from 25 to 100 W. Dialysate and perfusate ethanol concentrations were presented as the ratio of [ethanol]dialysate to [ethanol]perfusate (ethanol outflow-to-inflow ratio), an indicator that is inversely related to blood flow. The ethanol outflow-to-inflow ratios at rest were 0.614 +/- 0.032, 0.523 +/- 0.023, and 0.578 +/- 0.039 in the L-NMMA, L-arginine, and control probes, respectively. Calculated resting blood flows were therefore 8.7 +/- 4.1, 20.5 +/- 4.6, and 14.0 +/- 4.7 ml.min-1.100 g-1 around the L-NMMA, L-arginine, and control probes, respectively. The ethanol outflow-to-inflow ratios were significantly higher at all exercise intensities in the L-NMMA probe than in the control and L-arginine probes, resulting in calculated blood flows of 195 +/- 55, 407 +/- 47, and 352 +/- 60 ml.min-1.100 g-1 at 25 W and 268 +/- 65, 602 +/- 129, and 519 +/- 113 ml.min-1.100 g-1 at 100 W around the L-NMMA, L-arginine, and control probes, respectively. Skeletal muscle blood flow was therefore reduced both at rest and during continuous, dynamic exercise by the action of L-NMMA, whereas blood flow was increased only at rest by L-arginine.


2004 ◽  
Vol 97 (3) ◽  
pp. 1130-1137 ◽  
Author(s):  
Csongor Csekő ◽  
Zsolt Bagi ◽  
Akos Koller

We hypothesized that hydrogen peroxide (H2O2) has a role in the local regulation of skeletal muscle blood flow, thus significantly affecting the myogenic tone of arterioles. In our study, we investigated the effects of exogenous H2O2 on the diameter of isolated, pressurized (at 80 mmHg) rat gracilis skeletal muscle arterioles (diameter of ∼150 μm). Lower concentrations of H2O2 (10−6–3 × 10−5 M) elicited constrictions, whereas higher concentrations of H2O2 (6 × 10−5–3 × 10−4 M), after initial constrictions, caused dilations of arterioles (at 10−4 M H2O2, −19 ± 1% constriction and 66 ± 4% dilation). Endothelium removal reduced both constrictions (to −10 ± 1%) and dilations (to 33 ± 3%) due to H2O2. Constrictions due to H2O2 were completely abolished by indomethacin and the prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor antagonist SQ-29548. Dilations due to H2O2 were significantly reduced by inhibition of nitric oxide synthase (to 38 ± 7%) but were unaffected by clotrimazole or sulfaphenazole (inhibitors of cytochrome P-450 enzymes), indomethacin, or SQ-29548. In endothelium-denuded arterioles, clotrimazole had no effect, whereas H2O2-induced dilations were significantly reduced by charybdotoxin plus apamin, inhibitors of Ca2+-activated K+ channels (to 24 ± 3%), the selective blocker of ATP-sensitive K+ channels glybenclamide (to 14 ± 2%), and the nonselective K+-channel inhibitor tetrabutylammonium (to −1 ± 1%). Thus exogenous administration of H2O2 elicits 1) release of PGH2/TxA2 from both endothelium and smooth muscle, 2) release of nitric oxide from the endothelium, and 3) activation of K+ channels, such as Ca2+-activated and ATP-sensitive K+ channels in the smooth muscle resulting in biphasic changes of arteriolar diameter. Because H2O2 at low micromolar concentrations activates several intrinsic mechanisms, we suggest that H2O2 contributes to the local regulation of skeletal muscle blood flow in various physiological and pathophysiological conditions.


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Zachary Barrett‐O'Keefe ◽  
Stephen J. Ives ◽  
Joel D. Trinity ◽  
Melissa A.H. Witman ◽  
Matthew J. Rossman ◽  
...  

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Ilkka Heinonen ◽  
Kari Kalliokoski ◽  
Vesa Oikonen ◽  
Christopher Mawhinney ◽  
Warren Gregson ◽  
...  

Objective Skeletal muscle is unique among organs in that its blood flow, thus oxygen supply that is critical for muscular function, can change over a remarkably large range. Compared to the rest, muscle blood flow can increase over 20-fold during intense exercise. Positron emission tomography (PET) and [15O]-H2O tracer provide a unique tool for the direct measurement of muscle blood flow in specific muscle regions. Quantification of PET blood flow requires knowledge of the arterial input function, which is usually provided by arterial blood sampling. However, arterial sampling is an invasive approach requiring arterial cannulation. In the current study, we aimed to explore the analysis and error estimation based on non-invasive, PET image-based input function for skeletal muscle blood flow in PET [15O]-labeled radiowater study. Methods Thirty healthy untrained men volunteered to participate in this study. [15O]-labeled radio water PET perfusion scans were performed at rest and right after cycling exercise. GE Discovery PET-CT scanner was used for image acquisition. The 15O isotope was produced with a Cyclone 3 cyclotron (IBA Molecular, Belgium). After 455 MBq of 15O-H2O was injected intravenously and after 20 seconds, dynamic scanning images were performed in following frames: 6x5 seconds, 12x10 seconds, 7x30 seconds and 12x10 seconds. Arterial blood was sampled continuously from radial artery during imaging for radioactivity with a detector during PET scanning. All the data analysis was performed using all in-house developed programs. Arterial input function was preprocessed with delay correction. Image-based input function was defined based on sum image of dynamic images. Blood flow was calculated using the 1-tissue compartment model, k1 is considered as blood flow without any further correction. All data analysis was performed by Carimas software (http://www.turkupetcentre.fi/carimas). Data analysis was performed in five parts: 1) Modelling data using input function from artery. 2) By defining femoral artery Volume Of Interest (VOI) on PET images. 3) Modelling data using image-based input function. 4) Calculating the correlation for blood flow between artery (blood) input function and image-based input function. 5) Predicted true blood flow was calculated based on correlation based on the initial linear relationship between blood and image-based input functions. Results Skeletal muscle blood flow had a good linear relationship calculated by femoral artery VOI and by arterial (blood) input function (y = 2,9587x - 0,096, R² = 0,8852, p<0.0001). Further, by using the prediction equation obtained by the linear relationship between VOI-determined (femoral) artery blood flow and direct gold standard (radial) artery input function determined blood flow, image-based input function determined blood flow was well predicted using this non-invasive approach (y = 1,1812x + 0,1219, R² = 0,9259, p<0.0001). Conclusions It is concluded that there is a strong linear correlation between gold standard invasive approach and non-invasive image-based approach to measure skeletal muscle blood flow by PET, but if no further corrections are made, image-based approach overestimates correct blood flow. However, this can be corrected by linear prediction equation, suggesting that invasive arterial input function may not always be needed in the future when measuring skeletal muscle blood flow by PET. This will be of benefit particularly for exercise studies.


Author(s):  
Miles F. Bartlett ◽  
Scott M. Jordan ◽  
Dennis M. Hueber ◽  
Michael D. Nelson

Near-infrared diffuse correlation spectroscopy (DCS) is increasingly utilized to study relative changes in skeletal muscle blood flow. However, most diffuse correlation spectrometers assume that tissue optical properties- such as absorption (μa) and reduced scattering (μ's) coefficients- remain constant during physiological provocations, which is untrue for skeletal muscle. Here, we interrogate how changes in tissue μa and μ's affect DCS calculations of blood flow index (BFI). We recalculated BFI using raw autocorrelation curves and μa/μ's values recorded during a reactive hyperemia protocol in 16 healthy young individuals. First, we show that incorrectly assuming baseline μa and μ's substantially affects peak BFI and BFI slope when expressed in absolute terms (cm2/s, p<0.01) but these differences are abolished when expressed in relative terms (% baseline). Next, to evaluate the impact of physiologic changes in μa and μ's, we compared peak BFI and BFI slope when μa and μ's were held constant throughout the reactive hyperemia protocol versus integrated from a 3s-rolling average. Regardless of approach, group means for peak BFI and BFI slope did not differ. Group means for peak BFI and BFI slope were also similar following ad absurdum analyses, where we simulated supraphysiologic changes in μa/μ's. In both cases, however, we identified individual cases where peak BFI and BFI slope were indeed affected, with this result being driven by relative changes in μa over μ's. Overall, these results provide support for past reports in which μa/μ's were held constant but also advocate for real-time incorporation of μa and μ's moving forward.


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