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Biomedical subjects

E E Wolfel

Publications and source records attributed to E E Wolfel.

At least 19 recordsLinked to original sources
PubMed2001

Predicting response to carvedilol for the treatment of heart failure: a multivariate retrospective analysis.

BACKGROUND: Carvedilol has been shown to decrease the progression of heart failure and improve left ventricular function and survival in patients with a left ventricular ejection fraction (LVEF) less than 35%. However, not all patients respond uniformly to this therapy. We proposed to identify variables that could, potentially, be used to predict response to carvedilol therapy as measured by the change in LVEF after treatment (Delta LVEF), and to identify pretreatment variables associated with hospitalization for heart failure after carvedilol therapy. METHODS AND RESULTS: A retrospective analysis of 98 patients treated with open-label carvedilol for a mean period of 16 months was performed by using bivariate and step-wise multivariate analyses. Bivariate analysis showed a positive correlation of Delta LVEF with heart rate at baseline (P =.001). There was a negative correlation of Delta LVEF with baseline LVEF (P <.01), diabetes mellitus (P =.04), and ischemic cardiomyopathy (P =.0002). Multivariate analysis showed a positive correlation of Delta LVEF with heart rate at baseline (P =.01) and a negative correlation with initial LVEF (P =.02) and ischemic cardiomyopathy (P =.006). Variables associated with hospitalization after initiation of carvedilol therapy were New York Heart Association (NYHA) classification (P =.001), lower extremity edema (P =.001), presence of an S3 (P =.02), hyponatremia (P =.02), elevated blood urea nitrogen (BUN) (P =.002), atrial fibrillation (P =.001), diabetes mellitus (P =.02), and obstructive sleep apnea (P =.009). CONCLUSIONS: Heart failure patients with the lowest LVEF or the highest heart rate at baseline had the greatest gain in LVEF after treatment with carvedilol. Patients with ischemic cardiomyopathy derived less benefit. Patients with clinical evidence of decompensated heart failure were at greater risk for hospitalization after initiation of carvedilol therapy.

Adolescent↗
PubMed2001

Catecholamine responses to alpha-adrenergic blockade during exercise in women acutely exposed to altitude.

We have previously documented the importance of the sympathetic nervous system in acclimatizing to high altitude in men. The purpose of this investigation was to determine the extent to which alpha-adrenergic blockade affects the sympathoadrenal responses to exercise during acute high-altitude exposure in women. Twelve eumenorrheic women (24.7 +/- 1.3 yr, 70.6 +/- 2.6 kg) were studied at sea level and on day 2 of high-altitude exposure (4,300-m hypobaric chamber) in either their follicular or luteal phase. Subjects performed two graded-exercise tests at sea level (on separate days) on a bicycle ergometer after 3 days of taking either a placebo or an alpha-blocker (3 mg/day prazosin). Subjects also performed two similar exercise tests while at altitude. Effectiveness of blockade was determined by phenylephrine challenge. At sea level, plasma norepinephrine levels during exercise were 48% greater when subjects were alpha-blocked compared with their placebo trial. This difference was only 25% when subjects were studied at altitude. Plasma norepinephrine values were significantly elevated at altitude compared with sea level but to a greater extent for the placebo ( upward arrow 59%) vs. blocked ( upward arrow 35%) trial. A more dramatic effect of both altitude ( upward arrow 104% placebo vs. 95% blocked) and blockade ( upward arrow 50% sea level vs. 44% altitude) was observed for plasma epinephrine levels during exercise. No phase differences were observed across any condition studied. It was concluded that alpha-adrenergic blockade 1) resulted in a compensatory sympathoadrenal response during exercise at sea level and altitude, and 2) this effect was more pronounced for plasma epinephrine.

Adrenergic alpha-Agonists↗
PubMed2000

Sympathoadrenal responses to submaximal exercise in women after acclimatization to 4,300 meters.

The purpose of this investigation was to determine the sympathoadrenal response to exercise in women after acclimatization to high altitude. Sixteen eumenorrheic women (age, 23.6 +/- 1.2 years; weight, 56.2 +/- 4.3 kg) were studied at sea level and after 10 days of high-altitude exposure (4,300 m) in either the follicular (n = 11) or luteal (n = 5) phase. Subjects performed two 45-minute submaximal steady-state exercise tests (50% and 65% peak O2 consumption [VO2 peak]) at sea level on a bicycle ergometer. Exercise tests were also performed on day 10 of altitude exposure (50% VO2 peak at sea level). As compared with rest, plasma epinephrine levels increased 36% in response to exercise at 50% VO2 peak at sea level, with no differences found between cycle phases. This increase was significantly greater (increase 44%) during exercise at 65% VO2 peak. At altitude, the epinephrine response was identical to that found for 65% VO2 peak exercise at sea level (increase 44%), with no differences found between phase assignments. The plasma norepinephrine response differed from that for epinephrine such that the increase with exercise at altitude (increase 61%) was significantly greater compared with 65% Vo2 peak exercise at sea level (increase 49%). Again, no phase differences were observed. It is concluded that the sympathoadrenal response to exercise (1) did not differ between cycle phases across any condition and (2) was similar to that found previously in men, and (3) the relative exercise intensity is the primary factor responsible for the epinephrine response to exercise, whereas altitude had an additive effect on the norepinephrine response to exercise.

Adrenal Glands↗
PubMed2000

Endurance training increases gluconeogenesis during rest and exercise in men.

The hypothesis that endurance training increases gluconeogenesis (GNG) during rest and exercise was evaluated. We determined glucose turnover with [6,6-(2)H]glucose and lactate incorporation into glucose by use of [3-(13)C]lactate during 1 h of cycle ergometry at two intensities [45 and 65% peak O(2) consumption (VO(2 peak))] before and after training [65% pretraining VO(2 peak)], same absolute workload (ABT), and 65% posttraining VO(2 peak), same relative intensity (RLT). Nine males (178.1 +/- 2.5 cm, 81.8 +/- 3.3 kg, 27.4 +/- 2.0 yr) trained for 9 wk on a cycle ergometer 5 times/wk for 1 h at 75% VO(2 peak). The power output that elicited 66.0 +/- 1.1% of VO(2 peak) pretraining elicited 54.0 +/- 1.7% posttraining. Rest and exercise arterial glucose concentrations were similar before and after training, regardless of exercise intensity. Arterial lactate concentration during exercise was significantly greater than at rest before and after training. Compared with 65% pretraining, arterial lactate concentration decreased at ABT (4.75 +/- 0.4 mM, 65% pretraining; 2.78 +/- 0.3 mM, ABT) and RLT (3.76 +/- 0.46 mM) (P < 0.05). At rest after training, the percentage of glucose rate of appearance (R(a)) from GNG more than doubled (1.98 +/- 0.5% pretraining; 5.45 +/- 1.3% posttraining), as did the rate of GNG (0.11 +/- 0.03 mg x kg(-1) x min(-1) pretraining, 0.24 +/- 0.06 mg x kg(-1) x min(-1) posttraining). During exercise after training, %glucose R(a) from GNG increased significantly at ABT (2.3 +/- 0.8% at 65% pre- vs. 7.6 +/- 2.1% posttraining) and RLT (6.1 +/- 1.5%), whereas GNG increased almost threefold (P < 0.05) at ABT (0.24 +/- 0.08 mg x kg(-1) x min(-1) 65% pre-, and 0.71 +/- 0.18 mg x kg(-1) x min(-1) posttraining) and RLT (0.75 +/- 0.26 mg x kg(-1) x min(-1)). We conclude that endurance training increases gluconeogenesis twofold at rest and threefold during exercise at given absolute and relative exercise intensities.

Adult↗
PubMed2000

Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle.

To evaluate the effects of endurance training on the expression of monocarboxylate transporters (MCT) in human vastus lateralis muscle, we compared the amounts of MCT1 and MCT4 in total muscle preparations (MU) and sarcolemma-enriched (SL) and mitochondria-enriched (MI) fractions before and after training. To determine if changes in muscle lactate release and oxidation were associated with training-induced changes in MCT expression, we correlated band densities in Western blots to lactate kinetics determined in vivo. Nine weeks of leg cycle endurance training [75% peak oxygen consumption (VO(2 peak))] increased muscle citrate synthase activity (+75%, P < 0.05) and percentage of type I myosin heavy chain (+50%, P < 0.05); percentage of MU lactate dehydrogenase-5 (M4) isozyme decreased (-12%, P < 0.05). MCT1 was detected in SL and MI fractions, and MCT4 was localized to the SL. Muscle MCT1 contents were consistent among subjects both before and after training; in contrast, MCT4 contents showed large interindividual variations. MCT1 amounts significantly increased in MU, SL, and MI after training (+90%, +60%, and +78%, respectively), whereas SL but not MU MCT4 content increased after training (+47%, P < 0.05). Mitochondrial MCT1 content was negatively correlated to net leg lactate release at rest (r = -0.85, P < 0.02). Sarcolemmal MCT1 and MCT4 contents correlated positively to net leg lactate release at 5 min of exercise at 65% VO(2 peak) (r = 0.76, P < 0.03 and r = 0. 86, P < 0.01, respectively). Results support the conclusions that 1) endurance training increases expression of MCT1 in muscle because of insertion of MCT1 into both sarcolemmal and mitochondrial membranes, 2) training has variable effects on sarcolemmal MCT4, and 3) both MCT1 and MCT4 participate in the cell-cell lactate shuttle, whereas MCT1 facilitates operation of the intracellular lactate shuttle.

Adult↗
PubMed1999

Evaluation of exercise and training on muscle lipid metabolism.

To evaluate the hypothesis that endurance training increases intramuscular triglyceride (IMTG) oxidation, we studied leg net free fatty acid (FFA) and glycerol exchange during 1 h of cycle ergometry at two intensities before training [45 and 65% of peak rate of oxygen consumption (V(O2) peak)] and after training [65% pretraining V(O2) peak, same absolute workload (ABT), and 65% posttraining V(O2) peak, same relative intensity (RLT)]. Nine male subjects (178.1 +/- 2.5 cm, 81.8 +/- 3.3 kg, 27.4 +/- 2.0 yr) were tested before and after 9 wk of cycle ergometer training, five times per week at 75% V(O2) peak. The power output that elicited 66.1 +/- 1.1% of V(O2) peak before training elicited 54.0 +/- 1.7% after training due to a 14.6 +/- 3.1% increase in V(O2) peak. Training significantly (P < 0.05) decreased pulmonary respiratory exchange ratio (RER) values at ABT (0.96 +/- 0.01 at 65% pre- vs. 0.93 +/- 0.01 posttraining) but not RLT (0.95 +/- 0.01). After training, leg respiratory quotient (RQ) was not significantly different at either ABT (0.98 +/- 0.02 pre- vs. 0.98 +/- 0.03 posttraining) or RLT (1.01 +/- 0.02). Net FFA uptake was increased at RLT but not ABT after training. FFA fractional extraction was not significantly different after training or at any exercise intensity. Net glycerol release, and therefore IMTG lipolysis calculated from three times net glycerol release, did not change from rest to exercise or at ABT but decreased at the same RLT after training. Muscle biopsies revealed minor muscle triglyceride changes during exercise. Simultaneous measurements of leg RQ, net FFA uptake, and glycerol release by working legs indicated no change in leg FFA oxidation, FFA uptake, or IMTG lipolysis during leg cycling exercise that elicits 65% pre- and 54% posttraining V(O2) peak. Training increases working muscle FFA uptake at 65% V(O2) peak, but high RER and RQ values at all work intensities indicate that FFA and IMTG are of secondary importance as fuels in moderate and greater-intensity exercise.

Adult↗
PubMed1999

Muscle net glucose uptake and glucose kinetics after endurance training in men.

We evaluated the hypotheses that alterations in glucose disposal rate (R(d)) due to endurance training are the result of changed net glucose uptake by active muscle and that blood glucose is shunted to working muscle during exercise requiring high relative power output. We studied leg net glucose uptake during 1 h of cycle ergometry at two intensities before training [45 and 65% of peak rate of oxygen consumption (VO(2 peak))] and after training [65% pretraining VO(2 peak), same absolute workload (ABT), and 65% posttraining VO(2 peak), same relative workload (RLT)]. Nine male subjects (178.1 +/- 2.5 cm, 81.8 +/- 3.3 kg, 27.4 +/- 2.0 yr) were tested before and after 9 wk of cycle ergometer training, five times a week at 75% VO(2 peak). The power output that elicited 66.0 +/- 1.1% of VO(2 peak) before training elicited 54.0 +/- 1.7% after training. Whole body glucose R(d) decreased posttraining at ABT (5.45 +/- 0.31 mg. kg(-1). min(-1) at 65% pretraining to 4.36 +/- 0.44 mg. kg(-1). min(-1)) but not at RLT (5.94 +/- 0.47 mg. kg(-1). min(-1)). Net glucose uptake was attenuated posttraining at ABT (1.87 +/- 0.42 mmol/min at 65% pretraining and 0.54 +/- 0.33 mmol/min) but not at RLT (2.25 +/- 0. 81 mmol/min). The decrease in leg net glucose uptake at ABT was of similar magnitude as the drop in glucose R(d) and thus could explain dampened glucose flux after training. Glycogen degradation also decreased posttraining at ABT but not RLT. Leg net glucose uptake accounted for 61% of blood glucose flux before training and 81% after training at the same relative (65% VO(2 peak)) workload and only 38% after training at ABT. We conclude that 1) alterations in active muscle glucose uptake with training determine changes in whole body glucose kinetics; 2) muscle glucose uptake decreases for a given, moderate intensity task after training; and 3) hard exercise (65% VO(2 peak)) promotes a glucose shunt from inactive tissues to active muscle.

Adult↗
PubMed1999

Active muscle and whole body lactate kinetics after endurance training in men.

We evaluated the hypotheses that endurance training decreases arterial lactate concentration ([lactate](a)) during continuous exercise by decreasing net lactate release () and appearance rates (R(a)) and increasing metabolic clearance rate (MCR). Measurements were made at two intensities before [45 and 65% peak O(2) consumption (VO(2 peak))] and after training [65% pretraining VO(2 peak), same absolute workload (ABT), and 65% posttraining VO(2 peak), same relative intensity (RLT)]. Nine men (27.4 +/- 2.0 yr) trained for 9 wk on a cycle ergometer, 5 times/wk at 75% VO(2 peak). Compared with the 65% VO(2 peak) pretraining condition (4.75 +/- 0.4 mM), [lactate](a) decreased at ABT (41%) and RLT (21%) (P < 0.05). decreased at ABT but not at RLT. Leg lactate uptake and oxidation were unchanged at ABT but increased at RLT. MCR was unchanged at ABT but increased at RLT. We conclude that 1) active skeletal muscle is not solely responsible for elevated [lactate](a); and 2) training increases leg lactate clearance, decreases whole body and leg lactate production at a given moderate-intensity power output, and increases both whole body and leg lactate clearance at a high relative power output.

Adult↗
PubMed1998

Beta-adrenergic blockade does not prevent polycythemia or decrease in plasma volume in men at 4300 m altitude.

When humans ascend to high altitude (ALT) their plasma volume (PV) and total blood volume (BV) decrease during the first few days. With continued residence over several weeks, the hypoxia-induced stimulation of erythropoietin increases red cell production which tends to restore BV. Because hypoxia also activates the beta-adrenergic system, which stimulates red blood cell production, we investigated the effect of adrenergic beta-receptor inhibition with propranolol on fluid volumes and the polycythemic response in 11 healthy unacclimatized men (21-33 years old exposed to an ALT of 4300 m (barometric pressure 460 Torr) for 3 weeks on Pikes Peak, Colorado. PV was determined by the Evans blue dye method (PVEB), BV by the carbon monoxide method (BVCO), red cell volume (RCV) was calculated from hematocrit (Hct) and BVCO, and serum erythropoietin concentration ([EPO]) and reticulocyte count, were also determined. All determinations were made at sea level and after 9-11 (ALT-10) and 19-20 (ALT-20) days at ALT. At sea level and ALT, six men received propranolol (pro, 240 mg x day[-1]), and five received a placebo (pla). Effective beta-blockade did not modify the mean (SE) maximal values of [EPO] [pla: 24.9 (3.5) vs pro: 24.5 (1.5) mU x ml(-1)] or reticulocyte count [pla: 2.7 (0.7) vs pro: 2.2 (0.5)%]; nor changes in PVEB [pla: -15.8 (3.8) vs pro: -19.9 (2.8)%], RCVCO [pla: +7.0 (6.7) vs pro: + 10.1 (6.1)%], or BVCO [pla: -7.3 (2.3) vs pro: -7.1 (3.9)%]. In the absence of weight loss, a redistribution of body water with no net loss is implied. Hence, activation of the beta-adrenergic system did not appear to affect the hypovolemic or polycythemic responses that occurred during 3 weeks at 4300 m ALT in these subjects.

Adrenergic beta-Antagonists↗
PubMed1998

Poor relationship between arterial [lactate] and leg net release during exercise at 4,300 m altitude.

We evaluated the hypotheses that on acute exposure to hypobaric hypoxia, sympathetic stimulation leads to augmented muscle lactate production and circulating [lactate] through a beta-adrenergic mechanism and that beta-adrenergic adaptation to chronic hypoxia is responsible for the blunted exercise lactate response after acclimatization to altitude. Five control and 6 beta-blocked men were studied during rest and exercise at sea level (SL), on acute exposure to 4,300 m (A1), and after a 3-wk sojourn at altitude (A2). Exercise was by leg cycling at 49% of SL peak O2 consumption (VO2 peak) (65% of altitude VO2 peak or 87 +/- 2.6 W); beta-blockade was by propranolol (80 mg 3x daily), femoral arterial and venous blood was sampled; leg blood flow (Q) was measured by thermodilution, leg lactate net release [ = (2) (1-leg Q) venous-arterial concentrationL] was calculated, and vastus lateralis needle biopsies were obtained. Muscle [lactate] increased with exercise and acute altitude exposure but regressed to SL values with acclimatization; beta-blockade had no effect on muscle [lactate]. Arterial [lactate] rose during exercise at SL (0.9 +/- 0.1 to 1.5 +/- 0.3 mM); exercise at A1 produced the greatest arterial [lactate] (4.4 +/- 0.8 mM), and exercise at A2 an intermediate response (2.1 +/- 0.6 mM). beta-Blockade reduced circulating [lactate] approximately 45% during exercise under all altitude conditions. increased transiently at exercise onset but then declined over time under all conditions. Blood and muscle "lactate paradoxes" occurred independent of beta-adrenergic influences, and the hypotheses relating the blood lactate response at altitude to beta-adrenergic mechanisms are rejected. During exercise at altitude, arterial [lactate] is determined by factors in addition to hypoxemia, circulating epinephrine, and net lactate release from active muscle beds.

Acclimatization↗
PubMed1998

Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus.

Persons with type II diabetes mellitus (DM), even without cardiovascular complications have a decreased maximal oxygen consumption (VO2 max) and submaximal oxygen consumption (VO2) during graded exercise compared with healthy controls. We evaluated the hypothesis that change in the rate of VO2 in response to the onset of constant-load exercise (measured by VO2-uptake kinetics) was slowed in persons with type II DM. Ten premenopausal women with uncomplicated type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had a VO2 max test. On two separate occasions, subjects performed 7-min bouts of constant-load bicycle exercise at workloads below and above the lactate threshold to enable measurements of VO2 kinetics and heart rate kinetics (measuring rate of heart rate rise). VO2 max was reduced in subjects with type II DM compared with both lean and overweight controls (P < 0.05). Subjects with type II DM had slower VO2 and heart rate kinetics than did controls at constant workloads below the lactate threshold. The data suggest a notable abnormality in the cardiopulmonary response at the onset of exercise in people with type II DM. The findings may reflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.

Adult↗
PubMed1998

O2 extraction maintains O2 uptake during submaximal exercise with beta-adrenergic blockade at 4,300 m.

Whole body O2 uptake (VO2) during maximal and submaximal exercise has been shown to be preserved in the setting of beta-adrenergic blockade at high altitude, despite marked reductions in heart rate during exercise. An increase in stroke volume at high altitude has been suggested as the mechanism that preserves systemic O2 delivery (blood flow x arterial O2 content) and thereby maintains VO2 at sea-level values. To test this hypothesis, we studied the effects of nonselective beta-adrenergic blockade on submaximal exercise performance in 11 normal men (26 +/- 1 yr) at sea level and on arrival and after 21 days at 4,300 m. Six subjects received propranolol (240 mg/day), and five subjects received placebo. At sea level, during submaximal exercise, cardiac output and O2 delivery were significantly lower in propranolol- than in placebo-treated subjects. Increases in stroke volume and O2 extraction were responsible for the maintenance of VO2. At 4,300 m, beta-adrenergic blockade had no significant effect on VO2, ventilation, alveolar PO2, and arterial blood gases during submaximal exercise. Despite increases in stroke volume, cardiac output and thereby O2 delivery were still reduced in propranolol-treated subjects compared with subjects treated with placebo. Further reductions in already low levels of mixed venous O2 saturation were responsible for the maintenance of VO2 on arrival and after 21 days at 4,300 m in propranolol-treated subjects. Despite similar workloads and VO2, propranolol-treated subjects exercised at greater perceived intensity than subjects given placebo at 4,300 m. The values for mixed venous O2 saturation during submaximal exercise in propranolol-treated subjects at 4,300 m approached those reported at simulated altitudes >8,000 m. Thus beta-adrenergic blockade at 4,300 m results in significant reduction in O2 delivery during submaximal exercise due to incomplete compensation by stroke volume for the reduction in exercise heart rate. Total body VO2 is maintained at a constant level by an interaction between mixed venous O2 saturation, the arterial O2-carrying capacity, and hemodynamics during exercise with acute and chronic hypoxia.

Adrenergic beta-Agonists↗
PubMed1998

The association between diabetic complications and exercise capacity in NIDDM patients.

OBJECTIVE: Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It has been demonstrated previously in NIDDM patients that several risk factors (i.e., obesity, smoking, hypertension, and African-American race) are associated with an impaired exercise capacity. We studied 265 male and 154 female NIDDM patients who underwent graded exercise testing with expired gas analyses to determine the possible influences of diabetic neuropathy, nephropathy, and retinopathy on exercise capacity. RESEARCH DESIGN AND METHODS: Univariate and multiple linear regression analyses were performed to determine the relationship between diabetic neuropathy, urinary albumin excretion (UAE), and retinopathy with respect to peak oxygen consumption (VO2). Neuropathy was assessed by neurological symptom and disability scores, autonomic function testing, and quantitative sensory exams involving thermal and vibratory sensation. Three categories of UAE were used: normal albuminuria (< 20 micrograms/min), microalbuminuria (20-200 micrograms/min), and overt albuminuria (> 200 micrograms/min). Retinopathy was assessed by stereoscopic fundus photographs. Multiple linear regression analyses were then performed controlling for age, sex, length of diagnosed diabetes, duration of hypertension, race and ethnicity, GHb, BMI, and smoking to determine whether there was an independent effect of these diabetic complications on exercise capacity. RESULTS: Univariate analyses revealed that the presence of diabetic retinopathy (P = 0.03), neuropathy (P = 0.002), microalbuminuria (P = 0.04), and overt albuminuria (P = 0.06) were associated with a lower peak VO2. Multiple linear regression analyses were performed to determine independent relationships with peak VO2. The results revealed that increasing retinopathy stage (Parameter estimate [PE] = -0.59 +/- 0.3 ml.kg-1.min-1; P = 0.026) and increasing UAE stage (PE = -0.62 +/- 0.3 ml.kg-1.min-1; P = 0.04) were associated with a decrease in peak VO2. CONCLUSIONS: In the present study of NIDDM subjects, a significant independent association was demonstrated between diabetic nephropathy and retinopathy with exercise capacity. These results were obtained controlling for age, sex, length of diagnosed diabetes, hypertension, race, and BMI. Thus the findings in this large NIDDM population without a history of coronary artery disease indicate a potential pathogenic relationship between microvascular disease and exercise capacity.

Adult↗
PubMed1997

Relation of sympathetic activation to ventilation in man at 4300 m altitude.

BACKGROUND: The sympathetic nervous activity increases at high altitude but is not maximal initially when hypoxemia is most severe. HYPOTHESIS: The sympathetic activation would correlate better to the ventilatory response to chronic hypoxia than to the severity of hypoxia per se. METHODS: Eleven healthy male volunteers (27 +/- 1 yr) had measurements from the abdominal aorta of pressure, catecholamines, and blood gases at sea level, on arrival at 4300 m, and after 21 d of residence. Additionally, we measured 24-h urinary catecholamine excretion at sea level and each day at altitude, and made serial measurements of resting ventilatory parameters. RESULTS: Arterial norepinephrine (NE) concentrations on arrival at 4300 m were little changed from sea level, but were increased following acclimatization at 21 d. Arterial oxygenation was decreased on arrival, but improved with acclimatization. Arterial epinephrine (E) concentrations were increased on arrival, and returned to an intermediate level by 21 d. The urinary NE excretion was increased along with the increase in VE (p < 0.01) and the fall in end-tidal PCO2 (p < 0.001), but not with the decrease in end-tidal PO2 during the sojourn at 4300 m. Excretion of E did not relate to any ventilatory parameters. Propranolol (240 mg.d-1), which was given to 6 of 11 subjects, did not affect any relationships. CONCLUSION: The sympathetic activation was related to the ventilatory response but not to measures of hypoxemia at 4300 m. We conclude that factors related to ventilatory acclimatization, possibly increased chemoreceptor activity, contribute to the development of sympathetic activation at high-altitude.

Acclimatization↗
PubMed1996

Altitude and beta-blockade augment glucose utilization during submaximal exercise.

To test the hypothesis that altitude exposure increases glucose utilization and that this increment is mediated by a beta-adrenergic mechanism, the effects of hypobaric hypoxia and beta-blockade on glucose rates of appearance (Ra), disappearance (Rd), oxidation (Rox), and leg uptake [G = 2(arteriovenous glucose difference)(1 - leg blood flow)] were measured during rest and a given submaximal exercise task. We studied six healthy beta-blocked (beta) men [26.7 +/- 1.2 (SE) yr, 74.0 +/- 6.6 kg] and five matched controls (C; 26 +/- 1.2 yr, 69.3 +/- 2.6 kg) in energy and nitrogen balance during rest and leg cycle-ergometer exercise at sea level, on acute altitude exposure to 4,300 m (barometric pressure = 463 Torr), and after 3 wk of habituation. Subjects received a primed continuous infusion of [6,6-2H]- and [1-13C]glucose, rested for > or = 90 min, and then immediately exercised for 45 min at 89 W, which elicited 49% of sea-level peak O2 consumption (VO2peak; 65% of altitude VO2peak). At sea level, resting Ra was 1.47 +/- 0.19 and 1.66 +/- 0.16 mg x kg-1 x min-1 for C and beta, respectively, and increased to 3.04 +/- 0.25 and 3.56 +/- 0.27 mg x kg-1 x min-1, respectively, during exercise. Thus glucose Ra was significantly increased by beta-blockade during rest and exercise at sea level. At sea level, beta-blockade increased leg G, which accounted for 49 and 69% of glucose disposal during exercise in C and beta, respectively. On acute altitude exposure, glucose Ra rose significantly during rest and exercise relative to sea level, whereas blockade continued to augment this increment. During exercise on acute exposure, G increased more than at sea level and accounted for a greater percentage (80 and 97%, respectively) of Rd in C and beta during exercise. Similarly, Rox values, particularly during exercise, were increased significantly at altitude relative to sea level, and beta-blockade potentiated this effect. During a given submaximal exercise task after acclimatization, glucose Ra, Rox, and G were increased relative to sea level, but these increments were less than those in response to exercise measured on acute exposure. We conclude that altitude exposure increases glucose use during rest and a given submaximal exercise bout and beta-blockade exaggerates the response.

Adrenergic beta-Antagonists↗
PubMed1996

Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease.

Patients with symptomatic peripheral arterial occlusive disease have a claudication-limited peak exercise performance that is improved with exercise training. The effects of training on skeletal muscle metabolism were evaluated in 26 patients with claudication, randomized into a 12-wk program of treadmill training (enhances muscle metabolic activity in normal subjects), strength training (stimulates muscle hypertrophy in normal subjects), or a nonexercising control group. Gastrocnemius muscle biopsies were performed at rest and before and after training. After 12 wk, only treadmill training improved peak exercise performance and peak oxygen consumption. Treadmill training did not alter type I or type II fiber area and did not increase citrate synthase activity but was associated with an increase in the percentage of denervated fibers (from 7.6 +/- 5.4 to 15.6 +/- 7.5%, P < 0.05). Improvement in exercise performance with treadmill training was associated with a correlative decrease in the plasma (r = -0.67) and muscle (r = -0.59) short-chain acylcarnitine concentrations (intermediates of oxidative metabolism). Patients in the strength and control groups had no changes in muscle histology or carnitine metabolism, but strength-trained subjects had a decrease in citrate synthase activity. Thus treadmill training increased peak exercise performance, but this benefit was associated with skeletal muscle denervation and the absence of a "classic" mitochondrial training response (increase in citrate synthase activity). The present study confirms the relationship between skeletal muscle acylcarnitine content and function in peripheral arterial occlusive disease, demonstrating that the response to treadmill training was associated with parallel improvements in intermediary metabolism.

Aged↗
PubMed1996

Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate.

We tested the hypothesis that exposure to altitude decreases reliance on free fatty acids (FFA) as substrates and increases dependency on blood glucose. Therefore, the effects of exercise, hypobaric hypoxia, and altitude acclimatization on FFA, glycerol and net glucose uptake and release [= 2(leg blood flow)(arteriovenous concentration)] and on fatty acid (FA) consumption by the legs (= 3 x glycerol release + FFA uptake) were measured. Because sympathetic responses have been implicated, we utilized nonspecific beta-blockade and observed responses to exercise, altitude, and altitude acclimatization. We studied six healthy beta-blocked men (beta) and five matched controls (C) during rest and cycle ergometry exercise (88 W) at 49% of sea-level (SL) peak O2 uptake at the same absolute power output on acute altitude exposure (A1; barometric pressure = 430 Torr) and after 3 wk of chronic altitude exposure to 4,300 m (A2). During exercise at SL, FA consumption rates increased (P < 0.05). On arrival at 4,300 m, resting leg FFA uptake and FA consumption rates were not significantly different from those at SL. However, after acclimatization to altitude, at rest leg FA consumption decreased to essentially zero in both C and beta groups. During exercise to altitude after acclimatization, leg FA consumption increased significantly, but values were less than at SL or A1 (P < 0.05), whereas glucose uptake increased relative to SL values. Furthermore, beta-blockade significantly increased glucose uptake relative to control. We conclude that 1) chronic altitude exposure decreases leg FA consumption during rest and exercise; 2) relative to SL FFA uptake decreases while glucose uptake increases during exercise at altitude; and 3) beta-blockade potentiates these effects.

Acclimatization↗