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Biomedical subjects

C S Fulco

Publications and source records attributed to C S Fulco.

At least 37 records · Page 2Linked to original sources

Effects of altitude (4300 m) on the pharmacokinetics of caffeine and cardio-green in humans.

The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardio-green (ICG) were examined in eight healthy males (23-35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg. kg-1) was administered as an intravenous bolus and caffeine (4 mg. kg-1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in a caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g.l-1.min-1), and increased clearance (117 vs 86 ml.min-1.70 kg-1). In ALT the area under the curve the ICG significantly decreased (85 vs 207 mg.l-1.min-1) and the volume of distribution and clearance increased (5.2 vs 2.4 l and 532 vs 234 ml.min-1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.

Administration, Oral↗

Quantitation of progressive muscle fatigue during dynamic leg exercise in humans.

There is virtually no published information on muscle fatigue, defined as a gradual decline in force-generating capacity, during conventional dynamic (D) leg exercise. To quantitate progression of fatigue, we developed 1) a model featuring integration of maximal voluntary static contraction (MVC) of knee extension (KE) muscles with ongoing DKE and 2) a device that allows frequent rapid transfer between DKE isolated to the quadriceps femoris muscles and measurement of KE MVC. Eight healthy men performed graded and submaximal constant work rate one-leg DKE to exhaustion while seated. Work rate, a product of a contraction rate (1 Hz), force measured at the ankle, and distance of ankle movement from 90 degrees to 150 degrees of KE, was precisely controlled. Lack of rise in myoelectric activity in biceps femoris of the active leg during DKE and MVC was consistent with restriction of muscle action to quadriceps femoris. The slope of the linear relationship between O2 uptake and work rate was 13.7 ml O2/W (r = 0.93). This slope and the increase of heart rate relative to increasing work intensity agreed with published values for D leg exercise. Test-retest values for O2 uptake were similar (P > 0.05) for matched DKE work rates. To track fatigue, MVC (90 degrees knee angle) was performed every 2 min of DKE. After 4 min of DKE at work rates corresponding to (mean +/- SE) 66 +/- 2, 78 +/- 2, and 100% of peak DKE O2 uptake, MVC fell to 95 +/- 3, 90 +/- 5, and 65 +/- 7%* of MVC of rested muscle, respectively (*P < 0.01 from previous work rates). Virtually identical declines in MVC were observed by the end of graded work rate DKE and submaximal constant work rate DKE tests. Quantitation of progressive muscle fatigue during D leg exercise provides a framework to study the effects of a variety of interventions on the fatigue process and may permit unique insights into the involved mechanisms.

Adolescent↗

Adductor pollicis muscle fatigue during acute and chronic altitude exposure and return to sea level.

Large muscle exercise performance is impaired during acute exposure to normobaric or hypobaric hypoxia, but the effects of hypoxic conditions on fatigue of isolated smaller muscle groups per se are poorly defined. We studied how acute and chronic altitude (ALT) exposure and post-ALT return to sea level (SL) affects voluntary strength and fatigue of the adductor pollicis muscle. Eight healthy men (mean age 28 yr) were studied on five separate occasions: at SL, on days 1 (acute) and 13 (chronic) at ALT (4,300 m), and on days 1 (post 1) and 3 or 4 (post 2) at SL after 20 days of residence at ALT. On each day, maximal voluntary contractions (MVCs) of the adductor pollicis were obtained before and at the end of each minute of submaximal intermittent contractions of the adductor pollicis (50% of MVC of rested muscle, 5 s of contraction/5 s of rest) until exhaustion, defined as the inability to exert or maintain 50% of rested MVC. MVC of rested muscle did not differ among days. Time to exhaustion was shorter at acute ALT [5.1 +/- 0.5 (SE) min] than at SL (7.4 +/- 0.8 min, P < 0.05) and tended to be shorter than at chronic ALT (6.6 +/- 0.7 min, P > 0.05). Compared with acute and chronic ALT, time to exhaustion was prolonged during post 1 (9.0 +/- 1.2 min, P < 0.05) but not post 2 (6.1 +/- 0.5 min, P > 0.05). We conclude that 1) MVC of rested adductor pollicis muscle is not impaired during or after ALT exposure, 2) compared with SL conditions, acute but not chronic ALT exposure leads to a more rapid decline in adductor pollicis MVC associated with submaximal contractions, and 3) time to exhaustion is prolonged for > or = 1 day after return from ALT.

Acclimatization↗

Effect of caffeine on submaximal exercise performance at altitude.

The purpose of this study was to determine if caffeine (CAF) could enhance exercise performance at high altitude (HA). Eight males (17 to 24 years) performed two submaximal endurance tests to exhaustion (ETX) while cycling at approximately 80% of their altitude-specific maximal aerobic power during each of three phases: 1) sea level (SL); 2) after 1 h (acute) at 4,300 m; and 3) after 2 weeks (chronic) at 4,300 m. Subjects received either CAF (4 mg.kg-1) or a placebo drink 1 h prior to each ETX bout at each phase in a double-blind crossover design. ETX was little affected during CAF treatment at SL (26.33 to 27.51 min, p = 0.21) but was increased by 54% (22.77 to 35.10 min, p = 0.004) during acute HA exposure and tended to improve (24%, 30.52 to 38.63 min, p = 0.084) during chronic HA exposure. The change in ETX during acute ALT could not be accounted for by differences in substrate metabolism, Q, diet, or RPE, but may have been due to either a CAF-induced increase in tidal volume or to a lessening of an ALT-induced impairment in muscular force production during submaximal exercise.

Adolescent↗

Effects of altitude acclimatization on fluid regulatory hormone response to submaximal exercise.

To determine the effect of altitude acclimatization on plasma levels of atrial natriuretic peptide (ANP) during submaximal exercise and its relationship with renin and aldosterone, seven male volunteers aged 17-23 yr exercised to exhaustion on a cycle ergometer at 80-85% of their maximum O2 uptake at sea level (SL; 50 m), during 1 h in a hypobaric chamber [acute altitude (AA); 4,300 m], and after 14 or 16 days of residence on the summit of Pikes Peak, CO [chronic altitude (CA); 4,300 m]. Plasma samples taken before exercise, 10 min after the start of exercise, and 5 min postexercise were analyzed for ANP, plasma renin activity (PRA), and aldosterone (ALDO). ANP showed a progressive increase from rest to postexercise [7.49 +/- 1.63 to 11.32 +/- 1.80 (SE) pmol/ml and 6.05 +/- 2.55 to 10.38 +/- 7.20 pmol/ml; P = 0.049, exercise] at SL and AA, respectively, but not at CA (P = 0.039, altitude). Similarly, PRA and ALDO rose from rest to postexercise (P < 0.001, exercise), but the rise in ALDO with exercise was less during AA than during SL and CA (P = 0.002, phase). The decreased ANP levels during exercise after altitude acclimatization, with no change in PRA and ALDO, suggest that ANP has little effect on PRA and ALDO under these conditions.

Acclimatization↗

Use of bioelectrical impedance to assess body composition changes at high altitude.

This study determined the feasibility of using bioelectrical impedance analysis (BIA) to assess body composition alterations associated with body weight (BW) loss at high altitude. The BIA method was also evaluated relative to anthropometric assessments. Height, BW, BIA, skinfold (SF, 6 sites), and circumference (CIR, 5 sites) measurements were obtained from 16 males (23-35 yr) before, during, and after 16 days of residence at 3,700-4,300 m. Hydrostatic weighings (HW) were performed pre- and postaltitude. Results of 13 previously derived prediction equations using various combinations of height, BW, age, BIA, SF, or CIR measurements as independent variables to predict fat-free mass (FFM), fat mass (FM), and percent body fat (%Fat) were compared with HW. Mean BW decreased from 84.74 to 78.84 kg (P less than 0.01). As determined by HW, FFM decreased by 2.44 kg (P less than 0.01), FM by 3.46 kg (P less than 0.01), and %Fat by 3.02% (P less than 0.01). The BIA and SF methods overestimated the loss in FFM and underestimated the losses in FM and %Fat (P less than 0.01). Only the equations utilizing the CIR measurements did not differ from HW values for changes in FFM, FM, and %Fat. It was concluded that the BIA and SF methods were not acceptable for assessing body composition changes at altitude.

Adult↗

Cardiocirculatory responses to upright tilt at sea level and high altitude.

A collaborative study was conducted to measure the cardiocirculatory responses to upright tilt in eight young men at sea level (SL); after 1h at 4300m simulated altitude (SA) and at 18h, 66h and 114h during residence at 4300m (HA). Heart rate (HR), stroke volume (SV), cardiac output (CO), calf blood flow (CBF), blood pressure (BP) and total peripheral resistance (TPR) were obtained during supine rest and after 13 min of 60 degrees head-up tilt using an impedance monitor and an electrosphygmomanometer. SL to HA changes in blood volume (BV) were calculated from hematocrit and hemoglobin values. Supine HR, TPR and BP were increased while SV, CO and CBP were reduced SL to HA (P less than .05). HR and BP in the upright position were increased SL to HA (P less than .05). The responses to tilt (delta supine to upright) were unaltered SL vs SA. With prolonged exposure, SV, CO, TPR and CBP responses to tilt were reduced (P less than .05). The reduced responses to tilt at HA were associated with a 10% decline in BV (P less than .01). It was concluded that the reduction in SV during tilt at SL and SA was compensated for by increases in HR and TPR in order to maintain BP. After 18h HA, BP in the upright position was maintained only by an increase in HR.

Adult↗

Symptomatology during hypoxic exposure to flame-retardant chamber atmospheres.

Hypoxia was studied in 12 men during 63-h exposures to 17 and 13% O2, with the subjects serving as their own controls by repeating the measurements in 21% O2. All test atmospheres were contaminated with 0.9% CO2 to simulate the condition of living aboard submarines. The mean SaO2's were 97-98% in all conditions of 21% O2, 96% in 17% O2 (n.s.), and 92% in 13% O2 (P less than 0.05). The blood concentrations of 2,3-diphosphoglycerate were elevated in 13 and 17% O2 (P less than 0.05). Seventeen percent O2 did not cause significant symptoms of environmental stress; however, 13% O2 caused symptoms of acute mountain sickness in 5 of 12 men. In the last 7 h of exposure to 17% O2, reduction of the barometric pressure to 576 Torr reduced the ambient PO2 to 98 Torr (similar to the PO2 of 13% O2 at normobaric pressure). This induced symptoms of acute mountain sickness in 3 of 11 men. All symptomatology and physiologic changes were reversed during recovery in 21% O2. Monitoring devices indicated the presence of volatile organic contaminants at a mean concentration of 6.1 ppm in the chamber atmosphere. Combustion tests in the occupied chamber showed that flame propagation was retarded by lowering the O2 concentration from 21 to 13-17%. We conclude that men can live comfortably in a normobaric, flame-retardant atmosphere consisting of 17% O2-0.9% CO2-6.1 ppm volatile organic compounds-balance N2.

2,3-Diphosphoglycerate↗

Mental performance during submaximal exercise in 13 and 17% oxygen.

Submarine crews live in atmospheres containing variable levels of O2 and CO2. Under these conditions, significant reduction of the O2 may impair mental function during physical exertion. Therefore, psychomotor performance was measured in exercising men during Hours 26 and 57 of exposure to 21, 17, and 13% O2 in a hypobaric chamber (each gas contained 0.9% CO2, balance N1). Sea-level pressure was used except when reduced to 576 Torr at Hour 57 in 17% O2 (hypobaric-17% O2). At Hour 26 the subjects exercised at 35 and 65% of predicted VO2max They were hypoxic during exercise in 17 and 13% O2, as indicated by reduced SaO2 values (P less than 0.05). The psychomotor test (timed arithmetic) was affected by the exposure condition (P less than 0.05) but not by the work rate. At Hour 57, subjects repeated the arithmetic task at rest and at 65% of predicted VO2max. SaO2 was reduced in hypobaric-17 and 13% O2 (P less than 0.05). The math scores were affected by the work rate (P less than 0.05) but not by the exposure condition. From post-hoc analyses we conclude that 17% O2 does not impair the timed arithmetic task during submaximal exercise at normobaric pressures.

Adult↗

Dexamethasone as prophylaxis for acute mountain sickness. Effect of dose level.

Rapid exposure of unacclimatized persons to high altitude causes the syndrome acute mountain sickness (AMS). Prophylactic treatment with frequent high doses of dexamethasone has been shown to prevent AMS. To determine whether lower, less frequent doses were effective in preventing AMS, 28 men between the ages of 18 and 32 were exposed to a simulated altitude of 4,570 m for 45 h in a hypobaric chamber on two occasions while taking one of three doses of dexamethasone (4 mg, 1 mg, or .25 mg every 12 h) or a placebo in a double-blind, crossover design. The 4-mg dose of dexamethasone reduced the incidence of AMS symptoms compared with placebo and the other dose levels. Dexamethasone did not alter fluid balance or plasma volume changes, but treatment with 1 mg and 4 mg suppressed cortisol secretion. There was no evidence of adrenal cortical suppression after treatment with dexamethasone or placebo 48 h after discontinuing altitude exposure and drug treatment. The results indicate that 4 mg of dexamethasone twice daily is an effective prophylactic treatment for AMS, while lower doses are relatively ineffective.

Adolescent↗

Effects of propranolol on acute mountain sickness (AMS) and well-being at 4,300 meters of altitude.

A number of physiological responses and adjustments occur at high altitude to compensate for hypoxia. We hypothesized that interference with one component of the normal compensatory process, the sympathetic nervous system, would hinder altitude acclimatization and thereby exacerbate acute mountain sickness (AMS) and compromise well-being. Twelve young males (21.2 +/- 0.4 years) received either 80 mg propranolol (PRO; n = 6) or placebo (PLA; n = 6), t.i.d. at sea level (SL) and during the first 15 d of a 19-d residence at 4,300 m (HA). Individuals were randomly assigned to each group. The Environmental Symptoms Questionnaire (ESQ) was administered at SL and twice daily (AM and PM) during the entire altitude exposure in order to assess AMS symptoms and subjective feelings of well-being. Supine heart rate (HR) was determined at rest twice at SL and four times at HA. HR in the PLA group increased 40% over SL values (57 +/- 3 to 80 +/- 4 beats/min) by day 7 at HA (p less than 0.01). HR in the PRO group did not increase above SL values during medication at HA. By 4 d after the medication administration was terminated, HR in the PRO group had increased and did not differ from the PLA group. Throughout the entire altitude exposure, ESQ scores for the PRO group were lower than or similar to the PLA group. Furthermore, cessation of PRO treatment did not result in a change in well-being. These findings suggested that interference with the normal acclimatization process by beta-adrenergic blockade did not exacerbate AMS or reduce feelings of well-being.

Acute Disease↗

Propranolol and the compensatory circulatory responses to orthostasis at high altitude.

Tachycardia has been shown to be an important response involved in the maintenance of cardiac output during orthostasis at high altitude. This study was undertaken to determine if tachycardia, mediated by beta-adrenergic sympathetic stimulation, actually represents an essential response. Twelve young, healthy male subjects were administered either 80 mg propranolol (n = 6) or placebo (n = 6), t.i.d. at sea level and for 3 days (d) prior to and during the first 15 d of a 19-d altitude sojourn (On Treatment). Individuals were randomly assigned to each group. Upright tilt tests were performed at sea level and at high altitude during days 2, 7, and 15 On Treatment. Subjects were also tilt-tested at sea level and on day 19 of the altitude exposure without placebo or propranolol administration (Off Treatment). Heart rate, stroke volume, calf blood flow, and blood pressure were obtained during supine rest and after 12 min of 60 degrees tilt. We found no differences between groups in any of the circulatory measurements at sea level and altitude while Off Treatment. During the On Treatment phases at sea level and altitude, propranolol caused reductions in heart rate and blood pressure values in each position (p less than 0.05). Supine and upright cardiac output, however, were found not altered due to compensatory increases in stroke volume (p less than 0.05). We concluded that tachycardia, both at rest and during upright tilt at high altitude is important, but not essential to maintain cardiac output.

Adult↗

Maximal cardiorespiratory responses to one- and two-legged cycling during acute and long-term exposure to 4300 meters altitude.

During exposure to altitudes greater than about 2200 m, maximal oxygen uptake (VO2max) is immediately diminished in proportion to the reduction in the partial pressure of oxygen in the inspired air. If the exposure lasts longer than a couple of days, an increase in arterial oxygen content (CaO2), due to a hemoconcentration and an increase in arterial oxygen saturation, occurs. However, there is also a reduction in maximal cardiac output (Qmax) at altitude which offsets the increase in CaO2 and, therefore, VO2max does not improve. The purpose of this investigation was to study the contribution of the increase in CaO2 to the working muscles without the potentially confounding problem of a reduced Qmax. The approach used was to have seven male subjects (aged 17 to 24 years) perform one- and two-legged VO2max tests on a cycle ergometer at sea level (SL, PIO2 = 159 Torr), after 1 h at 4300 m simulated altitude (SA, PIO2 = 94 Torr) and during two weeks of residence on the summit of Pikes Peak, CO. (PP, 4300 m, PIO2 = 94 Torr). Cardiac output limits maximal performance during two-legged cycling but does not limit performance during one-legged cycling. During the study, CaO2 changed from 189 +/- 3 (mean +/- SE) at SL to 161 +/- 4 ml.L-1 during SA (SL vs. SA, p less than 0.01) and to 200 +/- 6 ml.L-1 at PP (SL vs. PP, p less than 0.05; SA vs. PP, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Operation Everest. II: Nutrition and body composition.

Progressive body weight loss occurs during high mountain expeditions, but whether it is due to hypoxia, inadequate diet, malabsorption, or the multiple stresses of the harsh environment is unknown. To determine whether hypoxia due to decompression causes weight loss, six men, provided with a palatable ad libitum diet, were studied during progressive decompression to 240 Torr over 40 days in a hypobaric chamber where hypoxia was the major environmental variable. Caloric intake decreased 43.0% from 3,136 to 1,789 kcal/day (P less than 0.001). The percent carbohydrate in the diet decreased from 62.1 to 53.2% (P less than 0.001). Over the 40 days of the study the subjects lost 7.4 +/- 2.2 (SD) kg and 1.6% (2.5 kg) of the total body weight as fat. Computerized tomographic scans indicated that most of the weight loss was derived from fat-free weight. The data indicated that prolonged exposure to the increasing hypoxia was associated with a reduction in carbohydrate preference and body weight despite access to ample varieties and quantities of food. This study suggested that hypoxia can be sufficient cause for the weight loss and decreased food consumption reported by mountain expeditions at high altitude.

Adult↗

Hemodynamic and sympathoadrenal responses to altitude in humans: effect of dexamethasone.

Altitude exposure alters hemodynamics and sympathoadrenal function and elicits acute mountain sickness (AMS). Since dexamethasone prevents AMS and influences responsiveness to catecholamines, we studied hemodynamic and sympathoadrenal responses to 4,570 m simulated altitude in 8 subjects treated with dexamethasone or placebo. Mean pulse rates were less at altitude with dexamethasone (96.1 for placebo and 84.1 for dexamethasone; treatment-altitude interaction, p = 0.0045). Altitude led to a postural decline in mean arterial pressure (posture-altitude interaction, p = 0.0026), but this was not affected by dexamethasone. Dexamethasone reduced urinary epinephrine to a greater extent during altitude exposure (from 9.41 ng.mg-1 creatinine with placebo to 4.16 with dexamethasone) when compared with sea level (from 3.24 to 3.08). Urinary excretion of norepinephrine was unchanged at altitude. We conclude that acute altitude exposure is associated with stimulation of the adrenal medulla and not the sympathetic nervous system. Dexamethasone blocks the adrenal medullary response and blunts the pulse rate increase at altitude.

Adrenal Medulla↗

Altitude acclimatization attenuates plasma ammonia accumulation during submaximal exercise.

This study examined the effects of acclimatization to 4,300 m altitude on changes in plasma ammonia concentrations with 30 min of submaximal [75% maximal O2 uptake (VO2max)] cycle exercise. Human test subjects were divided into a sedentary (n = 6) and active group (n = 5). Maximal uptake (VO2max) was determined at sea level and at high altitude (HA; 4,300 m) after acute (t less than 24 h) and chronic (t = 13 days) exposure. The VO2max of both groups decreased 32% with acute HA when compared with sea level. In the sedentary group, VO2max decreased an additional 16% after 13 days of continuous residence at 4,300 m, whereas VO2max in the active group showed no further change. In both sedentary and active subjects, plasma ammonia concentrations were increased (P less than 0.05) over resting levels immediately after submaximal exercise at sea level as well as during acute HA exposure. With chronic HA exposure, the active group showed no increase in plasma ammonia immediately after submaximal exercise, whereas the postexercise ammonia in the sedentary group was elevated but to a lesser extent than at sea level or with acute HA exposure. Thus postexercise plasma ammonia concentration was decreased with altitude acclimatization when compared with ammonia concentrations following exercise performed at the same relative intensity at sea level or acute HA. This decrease in ammonia accumulation may contribute to enhanced endurance performance and altered substrate utilization with exercise following acclimatization to altitude.

Acclimatization↗

Effect of dexamethasone on symptoms of acute mountain sickness at Pikes Peak, Colorado (4,300 m).

In a previous controlled study, dexamethasone (DEX) was shown to prevent acute mountain sickness (AMS) during exposure to simulated high altitude. To determine the effect of DEX during actual altitude exposure, 16 young men were treated with either DEX (4 mg every 6 h) or placebo for 48 h prior to and 48 h after being rapidly transported from sea level to the summit of Pikes Peak, CO (4,300 m). Symptoms of AMS were evaluated twice daily at Pikes Peak using the Environmental Symptoms Questionnaire and a clinical assessment. During treatment the mean symptom scores were higher for subjects taking placebo in 18 out of 20 comparisons. On an individual basis, 60% of the subjects receiving placebo met the criteria for being "sick" compared to 31% of subjects receiving DEX. Beginning 24 h after cessation of treatment, DEX subjects experienced a progressive increase in symptom scores which lasted through the end of the altitude sojourn (day 6). The results indicate that DEX is an effective prophylactic treatment for AMS in an actual mountain environment, but that AMS symptoms can occur if the drug is stopped abruptly.

Acute Disease↗

The effect of naproxen on acute mountain sickness and vascular responses to hypoxia.

The role of prostaglandins in the pathogenesis of acute mountain sickness and two hypoxia-induced vascular responses was evaluated using the cyclooxygenase inhibitor naproxen. Eleven men spent 24 hours at sea level, followed by 34 hours of decompression to 428 mm Hg while receiving naproxen (N), 250 mg twice daily or placebo (P) in a double-blind crossover trial. Serum naproxen levels measured by high pressure liquid chromatography were not changed by hypoxia. The severity of acute mountain sickness (AMS) by the Environmental Symptom Questionnaire scores and observer assessment were unaffected by drug treatment. Retinal artery diameter measured from projected fundus photographs was increased after 27 hours at altitude (11.4 +/- .5 mm) vs. sea level (9.4 +/- .5 mm, p less than 0.05) during both trials. Upright mean arterial pressure fell after 6 hours at altitude (79 +/- 3 mm Hg during N and P vs. 92 +/- 3 at sea level, p less than 0.01). Minute ventilation, end expiratory alveolar PO2 and PCO2 did not differ between drug trials. This study suggests vasodilating prostaglandins do not have a major role in the genesis of AMS, hypoxia-induced retinal vasodilatation, or postural blood pressure responses in man.

Acute Disease↗