Temporal inhomogeneity in brachial artery blood flow during forearm exercise.

The purpose of this study was to measure the influences of muscle contraction and exercise intensity on brachial artery blood flow during incremental forearm wrist flexion exercise to fatigue. Twelve subjects performed incremental forearm exercise (increments of 0.1 W every 5 min) with their nondominant arms. Doppler waveforms and two-dimensional images of the brachial artery were recorded during the last 2 min of each stage. Exercise intensities were expressed as a percent of the maximal workload achieved (%WLmax). Blood flow was calculated during each of the concentric (CP), eccentric (EP), and recovery phases (RP) of the contraction cycle. Blood flow during the CP of the contraction did not increase above resting values (25.0 +/- 10.5 mL.min-1) at any intensity (100%WLmax = 21.6 +/- 6.5 mL.min-1). Conversely, blood flow during the EP and RP increased from 25.6 +/- 3.0 to 169.1 +/- 12.8 (P < 0.05), and from 24.7 +/- 3.1 to 137.9 +/- 19.5 mL.min-1 (P < 0.05), respectively from rest to maximal exercise. Time averaged blood flow increased linearly from rest to maximal exercise (75.3 +/- 26.3 to 334.6 +/- 141.6 mL.min-1, P < 0.05). Thus, a significant impairment in blood flow occurs with concentric contractions during forearm dynamic exercise. The implications of a temporal disparity in blood flow to oxygen delivery and skeletal metabolism during exercise are discussed.

Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia.

Acute mountain sickness (AMS) strikes those in the mountains who go too high too fast. Although AMS has been long assumed to be due solely to the hypoxia of high altitude, recent evidence suggests that hypobaria may also make a significant contribution to the pathophysiology of AMS. We studied nine healthy men exposed to simulated altitude, normobaric hypoxia, and normoxic hypobaria in an environmental chamber for 9 h on separate occasions. To simulate altitude, the barometric pressure was lowered to 432 +/- 2 (SE) mmHg (simulated terrestrial altitude 4,564 m). Normobaric hypoxia resulted from adding nitrogen to the chamber (maintained near normobaric conditions) to match the inspired PO2 of the altitude exposure. By lowering the barometric pressure and adding oxygen, we achieved normoxic hypobaria with the same inspired PO2 as in our laboratory at normal pressure. AMS symptom scores (average scores from 6 and 9 h of exposure) were higher during simulated altitude (3.7 +/- 0.8) compared with either normobaric hypoxia (2.0 +/- 0.8; P < 0.01) or normoxic hypobaria (0.4 +/- 0.2; P < 0.01). In conclusion, simulated altitude induces AMS to a greater extent than does either normobaric hypoxia or normoxic hypobaria, although normobaric hypoxia induced some AMS.

Insulin resistance limits glucose utilization and exercise tolerance in myophosphorylase deficiency and NIDDM.

Myophosphorylase deficiency [McArdle's disease (MD)] produces a defect in muscle glycogenolysis in which muscular work is limited by delivery of external sources of substrate, primarily glucose and nonesterified fatty acids, to meet energy demands associated with exercise. In the present study, we evaluated an unusual patient with both MD and non-insulin-dependent diabetes mellitus. We hypothesized that insulin resistance would limit transport of extracellular glucose to skeletal muscle during exercise, resulting in impaired exercise performance that was reversible by insulin infusion. The effect of a hyperinsulinemic "euglycemic" clamp on exercise tolerance was evaluated by in vivo 31P-magnetic resonance spectroscopy as well as total work performed. We observed that insulin infusion significantly increased the rate of systemic glucose utilization (P < 0.01) and also significantly decreased the ratio of inorganic phosphate to phosphocreatine (P < 0.001) during forearm exercise compared with the control study. Insulin clamp was also associated with an increase in total work performed (56%) during exercise. Our findings demonstrate that resistance to the biological actions of insulin, as occurs in type II diabetes mellitus, leads to a defect in glucose transport that limits the availability of extracellular glucose to exercising muscle. In our subject with a substrate-limited skeletal muscle metabolism (MD), reversal of this defect in insulin-dependent glucose transport by a hyperinsulinemic euglycemic clamp was associated with significant improvement in magnetic resonance spectroscopy parameters of skeletal muscle metabolism as well as exercise performance.

Changes in muscle proton transverse relaxation times and acidosis during exercise and recovery.

We studied changes in muscle proton (1H) transverse relaxation times (T2) by magnetic resonance imaging during exercise and compared these changes with alterations in muscle metabolism measured by phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Eleven subjects completed two trials of intermittent incremental forearm wrist flexion exercise requiring 30 contractions/min for 5 min, 7 min of recovery between stages, and 5-N load increments/stage. Between stages of the first trial, T2 images of muscle 1H were obtained. Muscle T2 increased from 27.3 +/- 1.1 (SD) ms at rest to 35.8 +/- 3.6 ms after volitional fatigue (P < 0.05), whereas less active wrist extensor muscle T2 remained unchanged (26.8 +/- 0.9 to 28.8 +/- 1.6 ms; P > 0.05). After localizing the predominant muscle recruited from the T2 images, subjects completed an identical trial at least 1 wk later but involving surface coil 31P-MRS of the T2-enhanced muscle to measure the H+ concentration ([H+]). Intramuscular [H+] of T2-enhancing muscle increased from 1.1 +/- 0.1 x 10(-7) M at rest to 4.1 +/- 2.0 x 10(-7) M after volitional fatigue. Both muscle T2 and intramuscular [H+] increased in a bimodal manner, with T2 increasing before muscle [H+] (P < 0.05). The correlation coefficient between the percent change in T2 and muscle [H+] during exercise was +0.74 (range 0.48-0.98; P < 0.05) and +0.47 during recovery. After 12 min of recovery, muscle [H+] decreased to 1.4 +/- 0.3 x 10(-7) M (P < 0.05), and T2 remained close to postexercise values (32.2 +/- 3.1 ms, P > 0.05). The data indicate that 1) the T2 increases during increases in exercise intensity are nonlinear, 2) the T2 increases during exercise are significantly correlated with increases in [H+], and 3) the slow recovery of T2 compared with [H+] indicates that [H+] has a minor contribution to the recovery in T2.

Prevalence estimates of alcohol problems in a Veterans Administration outpatient population: AUDIT vs. MAST.

Prior reports have indicated that the prevalence of alcohol-related problems in VA patients is significantly higher than that found in the general population. Prevalence rates, however, are likely to be affected by the screening instrument employed. A sample of 722 VA outpatients awaiting general medical and urgent care treatment was asked to complete two screening questionnaires: the World Health Organization's AUDIT and the brief MAST. Of 508 completed AUDITs, 55 (11%) scored above the cut-offs of 11 for harmful consumption, and 85 (17%) above the more liberal cut-off score of 8; whereas of 501 completed MASTs, 104 (21%) scored above the cut-off. Differences in identification rates are discussed.

A comparison of the effects of nifedipine and verapamil on exercise performance in patients with mild to moderate hypertension.

Twenty-four patients completed a double-blind, randomized clinical trial comparing the effects of nifedipine GITS (N) and verapamil SR (V) on blood pressure (BP) control and exercise performance. After a 2-week placebo phase, all subjects had measurements of VO2max, maximal workload, and endurance time. They were then randomized to either N (30 to 90 mg/day) or V (240 to 480 mg/day) and retested when BPs had stabilized. At rest, N lowered systolic (S) BP by 12 mm Hg (P = .02 compared to baseline) and diastolic (D) BP by 11 mm Hg (P = .001). V lowered SBP by 8 mm Hg (P = .013) and DBP by 11 mm Hg (P = .002). Neither drug affected resting heart rate. V significantly decreased resting epinephrine (P = .05) and there was a tendency for V to reduce norepinephrine (P = .07) and dopamine (P = .08). N tended to increase plasma renin activity (P = .07). During graded cycle ergometry N, compared with placebo, significantly lowered DBP at all exercise levels (P = .011), but had no significant effect on heart rate (HR), SBP, or heart rate pressure product (HRPP). Pulse pressure (PP) was significantly increased (P = .045), which was most noticeable at high exercise levels. Compared with placebo, V caused a marked reduction of exercise HR (P < .001), which was more pronounced at high levels, SBP (P = .004), DBP (P = .004), mean arterial pressure (MAP) (P = .001), and HRPP (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

A weighted least-squares method for nuclear magnetic resonance velocity imaging.

The phase method for velocity measurements in NMR imaging with more than two velocity encoding steps is discussed. The weighted least-squares method takes into account the variation in the accuracy of phase calculations at a voxel with the size of the velocity encoding gradients. We choose the weights so that the method is equivalent to the method of maximum-likelihood for high signal-to-noise ratios. We propose a method of implementation to minimize the problem of phase wrapping. We also discuss the number of velocity encoding steps, the choice of step size, and signal averaging, to improve the reproducibility of velocity measurements. Standard deviation images for the velocity have been calculated and used to reduce velocity noise by thresholding the velocity image.

Skeletal muscle response to exercise training in congestive heart failure.

To examine the ability of the skeletal muscle of congestive heart failure (CHF) patients to adapt to chronic exercise, five patients performed localized nondominant wrist flexor training for 28 d. Inorganic phosphate (Pi) and phosphocreatine (PCr) were monitored by magnetic resonance spectroscopy in both forearms at rest and during submaximal wrist flexion exercise at 6, 12, 24, and 36 J.min-1 before and after exercise training. Simultaneous measurements of limb blood flow were made by plethysmography at 12, 24, and 36 J.min-1. Forearm muscle mass and endurance were measured by magnetic resonance imaging and wrist flexion exercise before and after training. The Pi/PCr ratio and pH were calculated from the measured Pi and PCr. Exercise cardiac output, heart rate, plasma norepinephrine, and lactate measured during training were not elevated above resting values, confirming that training was localized to the forearm flexor muscles. After training, muscle bioenergetics, as assessed by the slope of the regression line relating Pi/PCr to submaximal workloads, were improved in the trained forearm of each patient, although muscle mass, limb blood flow, and pH were unchanged. Forearm endurance increased by greater than 260% after training. In the dominant untrained forearm, none of the measured indices were affected. We conclude that localized forearm exercise training in CHF patients improves muscle energetics at submaximal workloads in the trained muscle, an effect which is independent of muscle mass, limb blood flow, or a central cardiovascular response during training. These findings indicate that peripheral muscle metabolic and functional abnormalities in CHF can be improved without altering cardiac performance.

Training-induced skeletal muscle adaptations are independent of systemic adaptations.

To isolate the peripheral adaptations to training, five normal subjects exercised the nondominant (ND) wrist flexors for 41 +/- 11 days, maintaining an exercise intensity below the threshold required for cardiovascular adaptations. Before and after training, intracellular pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) were measured by 31P magnetic resonance spectroscopy. Also maximal O2 consumption (VO2 max), muscle mass, and forearm blood flow were determined by graded systemic exercise, magnetic resonance imaging, and venous occlusion plethysmography, respectively. Blood flow, Pi/PCr, and pH were measured in both forearms at rest and during submaximal wrist flexion at 5, 23, and 46 J/min. Training did not affect VO2 max, exercise blood flow, or muscle mass. Resting pH, Pi/PCr, and blood flow were also unchanged. After training, the ND forearm demonstrated significantly lower Pi/PCr at 23 and 46 J/min. Endurance, measured as the number of contractions to exhaustion, also was increased significantly (63%) after training in the ND forearm. We conclude that 1) forearm training results in a lower Pi/PCr at identical submaximal work loads; 2) this improvement is independent of changes in VO2 max, muscle mass, or limb blood flow; and 3) these differences are associated with improved endurance and may reflect improved oxidative capacity of skeletal muscle.

Forearm metabolic asymmetry detected by 31P-NMR during submaximal exercise.

This study evaluated the relationship of skeletal muscle energy metabolism to forearm blood flow and muscle mass in the dominant (D) and nondominant (ND) forearms of normal subjects. 31P-Magnetic resonance spectroscopy was used to determine intracellular pH and the ratio of inorganic phosphate to phosphocreatine (Pi/PCr), an index of energy metabolism. Forearm blood flow and muscle mass were measured by venous occlusion plethysmography and magnetic resonance imaging, respectively. Metabolic measurements and flow were determined at rest and during submaximal exercise in both forearms. After a warm-up period, six normal right-handed male subjects performed 7.5 min of wrist flexion exercise in the magnet (1 contraction every 5 s), first with the ND forearm and then with the D forearm, at 23, 46, and 69 J/min. At rest, there were no differences between forearms in Pi/PCr or pH. However, at each work load the D forearm demonstrated significantly lower Pi/PCr and higher pH than the ND forearm. Blood flow was not significantly different between the forearms at rest or during exercise. Because these subjects were not engaged in unilateral arm training, we conclude that 1) Pi/PCr is lower and pH is higher in the D compared with the ND forearm in normal subjects during submaximal exercise, 2) these differences are independent of muscle mass and blood flow, and 3) the cumulative effect of long-term, low-level daily activity provides an adequate training stimulus for muscular metabolic adaptations.

Effects of pentoxifylline on pulmonary hemodynamics during acute hypoxia in anesthetized dogs.

The effects of pentoxifylline on pulmonary hemodynamics were studied in anesthetized dogs during acute alveolar hypoxia. In Series A, 7 dogs received pentoxifylline orally (18 mg/kg/day) for 11 wk and 7 untreated dogs served as control animals. During anesthesia and controlled ventilation, acute alveolar hypoxia was induced (10 to 13% inspired O2) and pulmonary and systemic hemodynamic and blood rheologic measurements were compared with normoxia. In control dogs, cardiac index did not change during hypoxia, but pulmonary vascular resistance index (PVRI) increased 79%, erythrocyte filterability decreased significantly (p less than 0.05), and relative viscosity of blood corrected for hematocrit did not change. In the pentoxifylline-treated dogs, cardiac index increased 28% and PVRI increased only 20%; in contrast to the control dogs, relative viscosity of blood was decreased by 18% and no significant changes in filterability were observed. The increase in PVRI in relation to the drop in arterial O2 saturation was significantly larger (p less than 0.05) in the control dogs. Pentoxifylline also increased P50 by 2.8 mm Hg (p less than 0.05). In Series B, hemodynamic measurements were made during variations in blood flow (induced by restricting venous return) in 3 treated (26 mg/kg/day for 3 wk) and 3 control dogs. In these experiments, pulmonary artery pressure was significantly lower at comparable flows during both normoxia and hypoxia. In both studies, the hemodynamic effects of the drug on the systemic circulation were less than on the pulmonary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)