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R C Hickner

Publications and source records attributed to R C Hickner.

32 records · Page 2Linked to original sources

Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic exercise in humans.

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.

Adult↗

Effect of endurance exercise training on muscle glycogen supercompensation in rats.

The purpose of this study was to test the hypothesis that the rate and extent of glycogen supercompensation in skeletal muscle are increased by endurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for an additional 2 wk. Glycogen repletion was measured in trained and untrained rats after a glycogen-depleting bout of exercise. The rats were given a rodent chow diet plus 5% sucrose in their drinking water and libitum during the recovery period. There were remarkable differences in both the rates of glycogen accumulation and the glycogen concentrations attained in the two groups. The concentration of glycogen in epitrochlearis muscle averaged 13.1 +/- 0.9 mg/g wet wt in the untrained group and 31.7 +/- 2.7 mg/g in the trained group (P < 0.001) 24 h after the exercise. This difference could not be explained by a training effect on glycogen synthase. The training induced approximately 50% increases in muscle GLUT-4 glucose transporter protein and in hexokinase activity in epitrochlearis muscles. We conclude that endurance exercise training results in increases in both the rate and magnitude of muscle glycogen supercompensation in rats.

Animals↗

Muscle glycogen accumulation after endurance exercise in trained and untrained individuals.

Muscle glycogen accumulation was determined in six trained cyclists (Trn) and six untrained subjects (UT) at 6 and either 48 or 72 h after 2 h of cycling exercise at approximately 75% peak O2 uptake (VO2 peak), which terminated with five 1-min sprints. Subjects ate 10 g carbohydrate . kg-1 . day-1 for 48-72 h postexercise. Muscle glycogen accumulation averaged 71 +/- 9 (SE) mmol/kg (Trn) and 31 +/- 9 mmol/kg (UT) during the first 6 h postexercise (P < 0.01) and 79 +/- 22 mmol/kg (Trn) and 60 +/- 9 mmol/kg (UT) between 6 and 48 or 72 h postexercise (not significant). Muscle glycogen concentration was 164 +/- 21 mmol/kg (Trn) and 99 +/- 16 mmol/kg (UT) 48-72 h postexercise (P < 0.05). Muscle GLUT-4 content immediately postexercise was threefold higher in Trn than in UT (P < 0.05) and correlated with glycogen accumulation rates (r = 0.66, P < 0.05). Glycogen synthase in the active I form was 2.5 +/- 0.5, 3.3 +/- 0.5, and 1.0 +/- 0.3 micromol . g-1 . min-1 in Trn at 0, 6, and 48 or 72 h postexercise, respectively; corresponding values were 1.2 +/- 0.3, 2.7 +/- 0.5, and 1.6 +/- 0.3 micromol . g-1 . min-1 in UT (P < 0.05 at 0 h). Plasma insulin and plasma C-peptide area under the curve were lower in Trn than in UT over the first 6 h postexercise (P < 0.05). Plasma creatine kinase concentrations were 125 +/- 25 IU/l (Trn) and 91 +/- 9 IU/l (UT) preexercise and 112 +/- 14 IU/l (Trn) and 144 +/- 22 IU/l (UT; P < 0.05 vs. preexercise) at 48-72 h postexercise (normal: 30-200 IU/l). We conclude that endurance exercise training results in an increased ability to accumulate muscle glycogen after exercise.

Adult↗

Muscle blood flow in cats: comparison of microdialysis ethanol technique with direct measurement.

A quantitative validation of the microdialysis ethanol technique was performed in cat gastrocnemius muscle. Six to eight microdialysis probes were inserted into the isolated muscle preparation and perfused (0.5-10.0 microliters/min) with Krebs-Henseleit buffer containing between 5 and 1,000 mmol/l ethanol. Skeletal muscle blood flow was held constant in the range of 4-99 ml.100 g-1.min-1 by a servo-controlled roller pump and was determined with the microdialysis ethanol technique as well as by timed collection of venous outflow. The ethanol concentration outflow-to-inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium) decreased in a nonlinear fashion when microdialysis perfusion flow rates of 0.5 and 1.0 microliter/min were employed. However, a linear decrease was found between 4 and approximately 45 ml.100 g-1.min-1 (r = -0.92 to -0.99). The lower outflow-to-inflow ratio was at 4 ml.100 g-1.min-1 (i.e., due to a low probe perfusion flow rate or a large dialysis membrane), the greater the sensitivity of the method was. It is concluded that this nonradioactive technique provides a simple and valid method for determining nutritive blood flow in skeletal muscle.

Animals↗

A mathematical model for measuring blood flow in skeletal muscle with the microdialysis ethanol technique.

A theoretical analysis of the microdialysis ethanol technique in skeletal muscle is presented, and a model governing the transport of ethanol from the microdialysis probe to the capillaries in the muscle tissue is proposed. The model is derived under the assumption of a steady-state situation, and an analytical solution is found for the outflow-to-inflow ratio of ethanol in the perfusate. Theoretically calculated results are compared with experiments, and for at least one of the two probe types used good agreement is achieved in a wide range of blood flow and perfusate flow rates. The main uncertainty factor in the theoretical calculations is the diffusivity of ethanol in muscle tissue, and the value for best agreement between theory and experiments has been used. Error estimates show that for a constant relative error in the outflow-to-inflow ratio of ethanol in the perfusate, low perfusate flow rates give better predictions of the blood flow.

Animals↗

Muscle blood flow during intermittent exercise: comparison of the microdialysis ethanol technique and 133Xe clearance.

1. Local skeletal muscle blood flow was monitored using the microdialysis ethanol technique and 133Xe clearance during intermittent isometric contractions (5 s on/10 s off) of the thigh at 0-60% of the maximal voluntary isometric contraction force. 2. A linear increase in blood flow over a 25-fold range was detected using both 133Xe clearance and the microdialysis ethanol technique. 3. The median correlation coefficient between percentage maximal voluntary isometric contraction force and the ethanol outflow/inflow ratio, a marker of blood flow, was r = -0.98 (-0.94 to -0.99) (median and range, n = 6). The corresponding correlation coefficient for 133Xe clearance was r = 0.97 (0.92-0.98), the correlation coefficient between the ethanol outflow/inflow ratio and 133Xe clearance being r = -0.92 (-0.89 to -0.94). 4. Dialysate glucose concentration, although affected by blood flow, was not always significantly correlated with blood flow changes (r = 0.70; 0.51-0.95). 5. It may be concluded that the ethanol technique provides a valid measure of changes in local skeletal muscle blood flow. The data furthermore show that a linear increase in thigh skeletal muscle blood flow exists during the studied protocol of intermittent isometric contractions.

Adult↗

Microdialysis of rat skeletal muscle and adipose tissue: dynamics of the interstitial glucose pool.

Microdialysis was evaluated as a method for studying glucose metabolism in skeletal muscle. Dialysis probes (0.5 x 10 mm) were perfused at 0.5 or 1.0 microliter min-1. Based upon perfusion with glucose, the muscle interstitial glucose concentration was estimated to be 6.9 +/- 0.3 mM (n = 14), which was not significantly different from the blood glucose level. With insulin infusion (1200 mU kg-1 body wt i.v.), the insulin-induced change in the glucose concentration of the interstitial space of muscle was of equal magnitude to that of blood and adipose tissue. In spite of this, when the perfusion medium was not supplemented with glucose, the glucose concentration decreased more in skeletal muscle dialysates (to 36.7 +/- 4.9% of the initial level) than in blood (to 29.7 +/- 5.0%) but less than in adipose tissue (to 17.7 +/- 4.9% of the initial level) (P < 0.05). The results indicate that these differences are due to tissue-specific differences in the dynamic balance between the supply to, and removal from, the interstitial glucose pool. This balance is revealed as a result of the constant glucose drainage by the microdialysis probe. The present results show that, in skeletal muscle, increases in glucose uptake occur with a concomitant increase in tissue blood flow as revealed by the microdialysis ethanol technique, whereas in adipose tissue the glucose uptake increases in the absence of a corresponding increase in blood flow.

Adipose Tissue↗

Regulation of skeletal muscle blood flow during acute insulin-induced hypoglycemia in the rat.

The mechanism behind hyperemia in skeletal muscle during insulin-induced hypoglycemia was investigated in 42 anesthetized male Wistar rats using the microdialysis ethanol technique of monitoring nutritive blood flow. Microdialysis probes were inserted bilaterally into the gastrocnemius muscle and perfused with a modified Krebs-Henseleit buffer containing 20 mmol/l ethanol and one or more of the following compounds: propranolol (10(-6) mol/l), phentolamine (10(-6) mol/l), and calyculin A (1.0 mumol/l). Muscle blood flow increased, as indicated by a decrease in the ethanol outflow:inflow ratio (P < 0.001, n = 6), during hypoglycemia induced by a bolus intravenous infusion of insulin (680 mU/kg body wt). This increase was not present during normoglycemia or during hypoglycemia and local beta-adrenergic blockade via propranolol. However, the hyperemic response was potentiated during hypoglycemia and local alpha-adrenergic blockade via phentolamine. A normal hyperemic response to hypoglycemia was detected during simultaneous alpha- and beta-adrenergic blockade. This response was eliminated on further supplementation of the microdialysis perfusion medium with calyculin A. Therefore, although stimulation of the alpha- and beta-adrenergic receptors does occur during insulin-induced hypoglycemia, it is not essential for the induction of hyperemia in this state. It may be concluded that hyperinsulinemia results in vasodilatation during hypoglycemia, although hyperinsulinemia does not have an effect on skeletal muscle blood flow under normoglycemic conditions.

Acute Disease↗

The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis.

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.

2-Chloroadenosine↗

Eccentric exercise induces transient insulin resistance in healthy individuals.

Euglycemic-hyperinsulinemic clamps were performed on six healthy untrained individuals to determine whether exercise that induces muscle damage also results in insulin resistance. Clamps were performed 48 h after bouts of predominantly 1) eccentric exercise [30 min, downhill running, -17% grade, 60 +/- 2% maximal O2 consumption (VO2max)], 2) concentric exercise (30 min, cycle ergometry, 60 +/- 2% VO2max), or 3) without prior exercise. During the clamps, euglycemia was maintained at 90 mg/dl while insulin was infused at 30 mU.m-2.min-1 for 120 min. Hepatic glucose output (HGO) was determined using [6,6-2H]glucose. Eccentric exercise caused marked muscle soreness and significantly elevated creatine kinase levels (273 +/- 73, 92 +/- 27, 87 +/- 25 IU/l for the eccentric, concentric, and control conditions, respectively) 48 h after exercise. Insulin-mediated glucose disposal rate was significantly impaired (P less than 0.05) during the clamp performed after eccentric exercise (3.47 +/- 0.51 mg.kg-1.min-1) compared with the clamps performed after concentric exercise (5.55 +/- 0.94 mg.kg-1.min-1) or control conditions (5.48 +/- 1.0 mg.kg-1.min-1). HGO was not significantly different among conditions (0.77 +/- 0.26, 0.65 +/- 0.27, and 0.66 +/- 0.64 mg.kg-1.min-1 for the eccentric, concentric, and control clamps, respectively). The insulin resistance observed after eccentric exercise could not be attributed to altered plasma cortisol, glucagon, or catecholamine concentrations. Likewise, no differences were observed in serum free fatty acids, glycerol, lactate, beta-hydroxybutyrate, or alanine. These results show that exercise that results in muscle damage, as reflected in muscle soreness and enzyme leakage, is followed by a period of insulin resistance.

Adult↗

Test development for the study of physical performance in wrestlers following weight loss.

This study was conducted to develop a testing protocol which would determine the extent of upper-body power output decrements in subjects following weight loss. Five athletes who had trained via upper-body exercise performed a 6-minute variable intensity arm crank test on an isokinetic ergometer before and after a 3-day, 4.5% body weight loss. Blood samples were drawn from a forearm vein pre- and 1, 3, and 5 min post-arm cranking for assessment of lactate, pH, hemoglobin, and hematocrit. The work performed pre-weight loss was significantly (paired t-test, p less than 0.05) greater than that performed post-weight loss. Repeated measures ANOVA yielded no significant differences in blood variables; however, pre-weight loss lactate values were higher and hemoglobin, hematocrit, and pH values were lower than post-weight loss values. It was concluded that a 4.5% body weight reduction resulted in performance decrements during this arm crank test. Survey information obtained from collegiate wrestlers (n = 14) subsequently tested under this protocol indicates the physical demands of this test approximate the physical demands of actual wrestling competition. It would therefore be appropriate to use this protocol during future testing of wrestlers in weight loss studies.

Adult↗

Reduced training maintains performance in distance runners.

This investigation examined endurance runners during a 3-week reduction in training volume and frequency. Ten well-conditioned runners were monitored for 4 weeks while training at their normal weekly training distance (mean +/- SE) (81 +/- 5 km/week, 6 days/week). This period was designated as baseline training (BT). Sixty km/week were run at approximately 75% VO2max, and the remainder (21 km/week) at approximately 95% VO2max in the form of intervals and races. The runners then reduced weekly training volume (RT) by 70% of BT to 24 +/- 2 km/week and frequency by 17% to 5 days/week for 3 weeks. During RT 17 km/week was performed at approximately 75% VO2max and the remainder (7 km/week) at approximately 95% VO2max (intervals and races). The runners were tested weekly and performed 5-km races on a 200-m indoor track during Bt and after 2 and 3 weeks of RT. Maximal heart rate (HR) increased (P less than 0.05) by approximately 4 beats/min at RT week 3, which may have been associated with a decrease in estimated plasma volume (P less than 0.01) of 5.62 +/- 0.43%. Time to exhaustion during the VO2max tests increased (P less than 0.05) by 9.5% at RT week 3. No significant (P greater than 0.05) changes occurred with RT in body weight, % body fat, overall 5 km race times, VO2max, muscular power (vertical leap and Margaria power test), and citrate synthase activity (at 2 weeks of RT). No alterations in venous lactate, energy expenditure, and HR were observed during submaximal running at two speeds (approximately 65% and 85% VO2max) with RT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Weight loss, dietary carbohydrate modifications, and high intensity, physical performance.

Well trained subjects (N = 12) were studied before and after losing approximately 6% of body weight to determine whether physical performance could be maintained while consuming a hypocaloric, high percentage carbohydrate diet. During a 4-d period of weight loss, subjects were randomly assigned to a high carbohydrate (HC) or low carbohydrate (LC) diet. A crossover design was used; subjects were measured before (PRE) and after (POST) weight loss on both diets for a 6-min bout of high intensity arm cranking, weight, skinfold thickness, and profile of mood states (POMS). Hemoglobin, hematocrit, and glycerol concentrations were analyzed for resting blood samples, while lactate, pH, and base excess were analyzed for blood samples drawn at rest and 1, 3, and 5 min after arm cranking. A three-way ANOVA of sprint work revealed a weight loss effect, a diet by weight loss interaction, and an order by diet by weight loss interaction (P less than 0.05). Total sprint work (mean +/- SE) PRE and POST HC was 37.7 +/- 2.1 kJ and 37.4 +/- 2.2 kJ, respectively. Sprint work was higher for PRE LC vs POST LC, with mean values of 37.4 +/- 2.1 kJ and 34.4 +/- 2.2 kJ, respectively. Post-arm cranking lactate was significantly higher PRE compared to POST for both HC and LC. Post-exercise blood pH was lower (P less than 0.05) at PRE vs POST, with no diet effect. Regardless of the diet, POMS variables tension, depression, anger, fatigue, and confusion were significantly elevated from PRE to POST; vigor was significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗