Function of the diaphragm during exercise]

We evaluated the effect of global inspiratory muscle fatigue (GF) on respiratory muscle control during exercise at 30%, 60%, and 90% of maximal power output in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. Respiratory pressures, breathing pattern, and perceived breathlessness were measured. Induction of GF had no effect on the ventilatory parameters during mild and moderate exercise. It altered, however, ventilatory response to heavy exercise by increasing breathing frequency and minute ventilation, with minor changes in tidal volume. This was accompanied by an increase in perceived breathlessness. GF significantly increased both the tonic and phasic activities of abdominal muscles that allowed 1) the diaphragm to maintain its function while developing less pressure, 2) the same tidal volume with lesser shortening of the rib cage inspiratory muscles, and 3) relaxation of the abdominal muscles to contribute to lung inflation. The increased work performed by the abdominal muscles may, however, lead to a reduction in their strength. GF may impair exercise performance in some healthy subjects that is probably not related to excessive breathlessness or other ventilatory factors. The respiratory system is remarkably adaptable in maintaining ventilation during exercise even with impaired inspiratory muscle contractility.     

Glucose production, utilization, and cycling in response to moderate exercise in obese subjects with type 2 diabetes and mild hyperglycemia

The glucoregulatory and hormonal responses to moderate-intensity exercise (50% VO2max for 45 min) were examined in subjects with type 2 diabetes and mild hyperglycemia. We studied seven obese subjects with type 2 diabetes and seven lean and seven obese control subjects (fasting plasma glucose levels, 7.5 +/- 0.5, 4.8 +/- 0.1, and 5.2 +/- 0.1 mmol/l, respectively). Glucose production, utilization, and cycling (flux between glucose and glucose-6-phosphate [G-6-P]) were measured with [6-(3)H]glucose and [2-(3)H]glucose using the constant specific-activity method. Insulin levels decreased normally during exercise in diabetic subjects. Plasma glucose levels decreased in diabetic subjects, but remained constant in control subjects. Basal glucose production was not different among groups and increased similarly during exercise. The decrease in plasma glucose in diabetic subjects was due to greater glucose utilization (867 +/- 83 vs. 726 +/- 143 micromol x m(-2) x min(-1); P < 0.05). This was a consequence of the mass effect of hyperglycemia, since glucose metabolic clearance increased similarly in all groups. Glucose cycling, expressed as a percentage of total glucose output (i.e., flux through G-6-P) was elevated at rest (P < 0.01), but decreased during exercise (P < 0.01). The catecholamine response to exercise was blunted in diabetic subjects, presumably indicating autonomic dysfunction. In conclusion, during moderate-intensity exercise in obese diabetic subjects with mild hyperglycemia, 1) insulin secretory responses were normally regulated; 2) glucose homeostasis was different from that in nondiabetic subjects because glucose levels decreased during exercise; 3) the decrease in plasma glucose was due to greater-than-normal rates of glucose utilization, which were sustained by hyperglycemia; and 4) elevated basal rates of glucose cycling decreased during exercise, presumably because exercise simultaneously lowered plasma glucose, was associated with a blunted catecholamine response, and accentuated an underlying defect in hepatic glucokinase activity in type 2 diabetes.     

In vivo hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats

Juvenile spontaneously hypertensive rats (SHR) have higher plasma levels of catechols and markedly larger catechol responses to yohimbine than do normotensive Wistar-Kyoto rats, indicating increased sympathoadrenal outflow and increased alpha 2-adrenergic receptor-mediated restraint of peripheral catecholamine release during hypertension development in SHR. Yohimbine-induced catecholamine release and metabolism in the posterolateral hypothalamus of the brain were assessed in juvenile (6 to 7 weeks) and adult (15 to 16 weeks) SHR and Wistar-Kyoto rats. In vivo microdialysis was used to obtain samples for measurements of norepinephrine, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid in conscious animals before and after yohimbine injection (1 mg/kg IV) beginning 24 hours after probe implantation. Catecholamine synthesis was examined from elevations of 3,4-dihydroxyphenylalanine levels after probe perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. In adults, SHR had higher dialysate norepinephrine (277 +/- 38 versus 181 +/- 35 pg/mL), dihydroxyphenylglycol (3260 +/- 509 versus 2231 +/- 201 pg/mL), methoxyhydroxyphenylglycol (2659 +/- 369 versus 1890 +/- 144 pg/mL), and dihydroxyphenylacetic acid (46,312 +/- 5512 versus 13,187 +/- 1963 pg/mL) levels and markedly larger increases in 3,4-dihydroxyphenylalanine levels after NSD-1015 than Wistar-Kyoto rats. In juveniles, SHR had larger proportionate increments in microdialysate norepinephrine levels after yohimbine than Wistar-Kyoto rats (85% versus 25%). Although juvenile SHR and Wistar-Kyoto rats had similar NSD-1015-elicited increments in 3,4-dihydroxyphenylalanine levels, systemic yohimbine enhanced the NSD-1015-elicited 3,4-dihydroxyphenylalanine elevations in juvenile SHR but not in Wistar-Kyoto rats. These findings suggest augmented norepinephrine release and catecholamine synthesis in the posterolateral hypothalamus of adult SHR and augmented alpha 2-adrenergic receptor restraint of both norepinephrine release and catecholamine synthesis in juvenile SHR.     

Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure

OBJECTIVES: This study sought to establish the chemosensitivity of patients with chronic heart failure. BACKGROUND: The ventilatory response to exercise is often increased in patients with chronic heart failure, as characterized by the steeper regression slope relating minute ventilation to carbon dioxide output. We hypothesized that the sensitivity of chemoreceptors may be reset and may in part mediate the exercise hyperpnea seen in this condition. METHODS: Hypoxic and peripheral hypercapnic chemosensitivity were studied in 38 patients with chronic heart failure (35 men, 3 women; mean [+/-SE] age 60.2 +/- 1.3 years; radionuclide left ventricular ejection fraction 25.7 +/- 2.3%) and 15 healthy control subjects (11 men, 4 women; mean age 54.9 +/- 3.0 years) using transient inhalations of pure nitrogen and single breaths of 13% carbon dioxide, respectively. The change in chemosensitivity during mild exercise (25 W) was assessed in the first 15 patients and all control subjects. Central hypercapnic chemosensitivity was also characterized in 25 patients and 10 control subjects by the rebreathing of 7% carbon dioxide in 93% oxygen. Cardiopulmonary exercise testing was performed in all subjects. RESULTS: Maximal oxygen consumption was 16.6 +/- 0.9 versus 29.7 +/- 2.2 mol/kg per min (p < 0.0001), and the ventilation-carbon dioxide output regression slope was 37.2 +/- 1.5 versus 26.5 +/- 1.4 (p < 0.0001) in patients and control subjects, respectively. Hypoxic and central hypercapnic chemosensitivity were enhanced in patients (0.707 +/- 0.076 vs. 0.293 +/- 0.056 liters/min per % arterial oxygen saturation [SaO2], p = 0.0001 and 3.15 +/- 0.41 vs. 2.02 +/- 0.25 liters/min per mm Hg, p = 0.025, respectively) and correlated significantly with the ventilatory response to exercise. Hypoxic chemosensitivity was augmented during exercise in patients and in control subjects but remained higher in the former (1.530 +/- 0.27 vs. 0.685 +/- 0.12 liters/min per %SaO2, p = 0.01). The peripheral hypercapnic chemosensitivity of patients at rest and during exercise was similar to that in control subjects, consistent with its lesser contribution to overall carbon dioxide chemosensitivity. CONCLUSIONS: Enhanced hypoxic and central hypercapnic chemosensitivity may play a role in mediating the increased ventilatory response to exercise in chronic heart failure.     

Force-frequency relations in the failing rabbit heart and responses to adrenergic stimulation

Yohimbine, an alpha 2 adrenoreceptor antagonist, enhances norepinephrine (NE) release and increases sympathetic activity. We examined the behavioral, peripheral sympathetic and adrenocortical responses to oral yohimbine in seven healthy controls and 11 patients diagnosed with agoraphobia with panic attacks (PD). Patients did not differ in baseline cardiovascular or neuroendocrine measures from controls despite significantly higher baseline anxiety ratings. Placebo caused no changes in baseline-corrected behavioral, cardiovascular or neurochemical responses in either group. Yohimbine induced a panic episode in six PD patients, but no controls. PD patients had significantly higher severity scores of autonomic anxiety symptoms. Yohimbine significantly raised systolic blood pressure (F = 3.07, P < 0.03), plasma NE levels (F = 12.11, P < 0.00) and cortisol levels (F = 4.82, P < 0.02), but had no effect on epinephrine levels. NE responses were similar in both groups, but patients had higher cortisol responses to yohimbine than controls (F = 7.14, P < 0.01). The correlational pattern between behavioral ratings and neuroendocrine responses in patients was opposite to that observed in controls. Despite similar increases in plasma NE levels between PD patients and healthy controls, PD patients had greater anxiogenic, cardiovascular and cortisol responses to yohimbine. Enhanced post-synaptic adrenoreceptor sensitivity may explain the noradrenergic dysregulation found in panic disorder.     

Ventilatory support during exercise in patients with pulmonary tuberculosis sequelae

STUDY OBJECTIVE: The aim of this study was to determine whether intermittent positive pressure ventilation through a nasal mask (NIPPV) applied during exercise in patients with pulmonary tuberculosis sequelae (PTS) could improve arterial blood gas measurements, ameliorate breathlessness, and increase exercise endurance. PATIENTS: Seven PTS patients with a severe restrictive ventilatory defect (mean [SD] vital capacity, 1.02 [0.25] I) enrolled in this study had experienced NIPPV previously, and were familiar with the procedure. DESIGN: The patients underwent four constant-load cycle ergometer tests in the supine position to tolerance. The tests were performed with and without NIPPV, while breathing normoxic air (Air) or supplemental oxygen (O2; 35%). NIPPV was delivered during exercise in a controlled, volume-cycled mechanical ventilation mode, and the ventilator settings were modulated manually to meet patients' respiratory demands as estimated from the airway pressure waveform and the patient's breathlessness. RESULTS: All patients matched their breathing to the ventilator cycle during most of the exercise while receiving NIPPV. NIPPV significantly prolonged their exercise endurance time, from a mean (SD) of 180 (58) s to 310 (96) s in Air, and from 227 (64) s to 465 (201) s in O2. During exercise, NIPPV effectively decreased their breathlessness and significantly improved arterial blood gas measurements. CONCLUSIONS: NIPPV applied during exercise can effectively support ventilation, significantly ameliorate breathlessness, and consequently improve exercise endurance in patients with PTS.     

First total synthesis of ganglioside GT1a alpha

Controversy still exists concerning the potential ergogenic benefit of caffeine (CAF) for exercise performance. The purpose of this study was to compare the effects of CAF ingestion on endurance performance during exercise on a bicycle ergometer at two different intensities, i.e., approximately 10% below and 10% above the anaerobic threshold (AT). Eight untrained males, non-regular consumers of CAF, participated in this study. AT, defined as the intensity (watts) corresponding to a lactate concentration of 4 mM, was determined during an incremental exercise test from rest to exhaustion on an electrically braked cycle ergometer. On the basis of these measurements, the subjects were asked to cycle until exhaustion at two different intensities, i.e., approximately 10% below and 10% above AT. Each intensity was performed twice in a double-blind randomized order by ingesting either CAF (5 mg/kg) or a placebo (PLA) 60 min prior to the test. Venous blood was analyzed for free fatty acid, glucose, and lactate, before, during, and immediately after exercise. Rating of perceived exertion and time to exhaustion were also measured during each trial. There were no differences in free fatty acids or lactate levels between CAF and PLA during and immediately after exercise for either intensity. Immediately after exercise glucose increased in the CAF trial at both intensities. Rating of perceived exertion was significantly lower (CAF = 14.1 +/- 2.5 vs PLA = 16.6 +/- 2.4) and time to exhaustion was significantly higher (CAF = 46.54 +/- 8.05) min vs PLA = 32.42 +/- 14.81 min) during exercise below AT with CAF. However, there was no effect of CAF treatment on rating of perceived exertion (CAF = 18.0 +/- 2.7 vs PLA = 17.6 +/- 2.3) and time to exhaustion (CAF = 18.45 +/- 7.28 min vs PLA = 19.17 +/- 4.37 min) during exercise above AT. We conclude that in untrained subjects caffeine can improve endurance performance during prolonged exercise performed below AT and that the decrease of perceived exertion can be involved in this process.     

Does cold air affect exercise capacity and dyspnea in stable chronic obstructive pulmonary disease?

Cold air may worsen asthmatic bronchoconstriction but can lessen breathlessness in normal individuals. Patients with COPD sometimes report improvement in their dyspnea in cold weather. We examined the effect of breathing cold air on exercise tolerance and the perception of breathlessness in 19 patients with stable COPD (age [+/- SD], 63 +/- 6 years; FEV1, 0.99 +/- 0.28 L) in a randomized open study. Patients exercised on a cycle ergometer breathing either room or cold air (-13 degrees C), breathlessness being assessed by Borg scaling. Peak exercise performance improved when breathing cold air (mean +/- SE), 46 +/- 6 W compared with 37 +/- 7 W (p < 0.05) while end-exercise breathlessness fell from 4.6 +/- 0.4 compared with 4.1 +/- 0.5 (p < 0.05) when breathing cold air. End-exercise ETCO2 was higher breathing cold air (6.1 +/- 0.3 kPa compared with 5.5 +/- 0.3 kPa) (p < 0.005). There was no difference in breathlessness at equivalent levels of ventilation. Cold air reduces breathlessness in COPD, probably by inducing relative hypoventilation.     

Modification of exercise performance by sharp reduction of blood pressure. A study in patients with uncomplicated hypertension

We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.     

Nasal inhalation of l-menthol reduces respiratory discomfort associated with loaded breathing

To test the hypothesis that stimulation of cold receptors in the upper airway may alleviate the sensation of respiratory discomfort, we investigated the effects of nasal inhalation of l-menthol (a specific stimulant of cold receptors) on the respiratory sensation and ventilation during the loaded breathing in 11 normal subjects. Subjects were asked to rate their sensation of respiratory discomfort using a visual analog scale (VAS) while breathing on a device with a flow-resistive load (180 cm H2O/L/s) or with an elastic load (75.5 cm H2O/L). The effects of inhalation of l-menthol on ventilation and respiratory sensation were evaluated by comparing the steady-state values of ventilatory variables and VAS scores obtained before, during, and after l-menthol inhalation. In 8 of 11 subjects inhalation of strawberry-flavored air instead of l-menthol was performed during loaded breathing. Both during the flow-resistive loading and the elastic loading, inhalation of l-menthol caused a significant reduction in sensation of respiratory discomfort (flow-resistive loading: 62 +/- 14 [mean +/- SD] VAS units before inhalation versus 36 +/- 16 during inhalation, p < 0.01; elastic loading: 68 +/- 13 before inhalation versus 55 +/- 17 during inhalation, p < 0.01) without a significant change in breathing pattern and ventilation. Comparison of the effects between the flow-resistive loading and the elastic loading also revealed that the reduction in VAS score was more during the flow-resistive loading than during the elastic loading (p < 0.01). Inhalation of strawberry-flavored air caused neither changes in VAS score nor changes in breathing pattern and ventilation, indicating that olfaction is not a contributing factor in the relief of respiratory discomfort. We concluded that stimulation of cold receptors in the upper airway with nasal inhalation of l-menthol reduces the sensation of respiratory discomfort associated with loaded breathing. This effect is more effective during the flow-resistive loading than during the elastic loading.     

Orbital decompression in exophthalmos due to thyroid disease. Report of 69 cases]

Preclinical studies suggest that acoustic startle amplitude is increased during ethanol withdrawal. The current study evaluated the effects of intravenous infusion of the alpha 2-adrenergic antagonist, yohimbine (0.4 mg/kg), the serotonin partial agonist m-chlorophenylpiperazine (mCPP, 0.1 mg/kg), and placebo administered to 22 male patients meeting DSM-III-R criteria for alcohol dependence and 13 male healthy subjects. Patients and healthy subjects completed 3 test days under double-blind conditions in a randomized order. Patients were sober for 12-26 days prior to testing. On each test day, participants completed startle testing 80 min following drug infusion. Stimuli with varying intensities (90, 96, 102, 108, 114 dB) were presented in a randomized order balanced across four blocks. Stimuli consisted of 40-ms bursts of white noise administered every 45-60 s for 15-20 min through headphones. Analyses indicated that patients exhibited elevated acoustic startle magnitudes on the placebo day relative to healthy subjects. In patients, the magnitude of startle amplitudes elicited at 90 dB, but not 114 dB, correlated significantly with the number of previous alcohol detoxifications. Yohimbine increased startle magnitudes and reduced startle latencies relative to placebo and mCPP in both patients and healthy subjects. mCPP did not alter startle magnitude in either group. Yohimbine also increased the probability that a 90-dB stimulus produced a startle response in healthy subjects, but not in patients. Blunting of yohimbine effects on startle probability may reflect the baseline elevations in startle probability levels in patients, but may also be consistent with other evidence of reduced postsynaptic, but not presynaptic, noradrenergic function in these same patients. These data replicate and extend previous reports indicating that yohimbine facilitates the acoustic startle response in humans. They also further implicate the number of episodes of ethanol withdrawal as a factor influencing subsequent neurobiological responsivity in chronic alcoholic patients. Based on the current data, future research should explore whether measurement of the acoustic startle response provides an objective quantitative severity measure of ethanol withdrawal.     

The contribution of the reflex hypoxic drive to the hyperpnoea of exercise

Oxygen breath tests have been applied to six normal subjects at rest and during steady state exercise on a bicycle ergometer (200, 400 and 600 kpm) to estimate the contribution of the reflex hypoxic drive to total ventilation. The subjects were changed without their knowledge from air to 100% oxygen for 4--5 breaths, the fall in ventilation was recorded and expressed as a percentage of total ventilation (hypoxic drive). The average reflex hypoxic drive was 16.2% (SE +/- 2.6; n = 35) this remianed unaltered during all levels of steady state exercise. The maximum fall in ventilation occurred earlier in exercise (P less than 0.0005). At rest the maximum fall occurred on average 31.2 s (SE +/- 2.6) from the start of the first breath of oxygen. During the first level of steady state exercise the maximum fall occurred 19.4 s (SE +/- 0.5) from the start of the first breath of oxygen. It is concluded that the contribution of the reflex hypoxic drive to the total ventilation is unaltered by exercise although a substantial part of the hyperpnoea can be accounted for by the presence of this drive.     

Ventilation and respiratory mechanics during exercise in younger subjects breathing CO2 or HeO2

To determine if ventilation (VE) during maximal exercise would be increased as much by 3% CO2 loading as by resistive unloading of the airways, we studied seven subjects (39 +/- 5 years; mean +/- S.D.) during graded-cycle ergometry to exhaustion while breathing: (1) room air (RA); (2) 3% CO2, 21% O2, and 76% N2; or (3) 79% He and 21% O2). VE and respiratory mechanics were measured during each 1-min increment (20 or 30 W) in work rate. VE during maximal exercise was increased 21 +/- 17% when breathing 3% CO2 and 23 +/- 16% when breathing HeO2 (P < 0.01). Further, the ventilatory response to exercise above ventilatory threshold (VTh) was increased (P < 0.05) when breathing HeO2 (0.89 +/- 0.26 L/min/W) as compared with breathing RA (0.65 +/- 0.12). When breathing HeO2, end-expiratory lung volume (% total lung capacity, TLC) was lower during maximal exercise (46 +/- 7) when compared with RA (53 +/- 6, P < 0.01). In conclusion, VE during maximal exercise can be augmented equally by 3% CO2 loading as by resistive unloading of the airways in younger subjects. This suggests that in younger subjects with normal lung function there are minimal mechanical ventilatory constraints on VE during maximal exercise.     

Exercise mode and gender comparisons of energy expenditure at self-selected intensities

The purpose of this study was to compare oxygen consumption (VO2) and energy expenditure after 20 min of self-selected submaximal exercise for four modes of exercise. Eighteen subjects (9 male and 9 female) first completed a test of VO2max during treadmill running. On separate days, subjects then completed 20 min submaximal treadmill running (TR), simulated cross-country skiing (XC), cycle ergometry (CE), and aerobic riding (AR) exercise. Total VO2 and energy expenditure were significantly higher for TR than all other modes for both males and females (43.6 +/- 10.4, 39.1 +/- 9.7, 36.1 +/- 7.6, 28.4 +/- 6.1 LO2, for TR, XC, CE, and AR, respectively, P < 0.0001). For males and females, heart rate was similar during TR and XC and lower during CE and AR (154.8 +/- 14.2, 152 +/- 13.1, 143.4 +/- 14.9, and 126.2 +/- 12.0 beats.min-1 for TR, XC, CE, and AR, respectively, P < 0.0001). Compared with females, males had significantly greater VO2 (P < 0.005) and energy expenditure (P < 0.004), while females had higher heart rates (P < 0.003). Ratings of perceived exertion (RPE) were not different between TR, XC, and CE, but were significantly lower during AR (13.4 +/- 1.3, 13.6 +/- 0.8, 13.2 +/- 0.9, and 12.6 +/- 1.0 for TR, XC, CE, and AR, respectively, P < 0.003). TR elicited the greatest VO2 and energy expenditure during self-selected exercise despite and RPE similar to XC and CE. Therefore, treadmill exercise may be the modality of choice for individuals seeking to improve cardiorespiratory endurance and expend a larger number of kjoules.     

Responses of the red blood cells from two high-energy-demand teleosts, yellowfin tuna (Thunnus albacares) and skipjack tuna (Katsuwonus pelamis), to catecholamines

In fishes, catecholamines increase red blood cell intracellular pH through stimulation of a sodium/proton (Na+/H+) antiporter. This response can counteract potential reductions in blood O2 carrying capacity (due to Bohr and Root effects) when plasma pH and intracellular pH decrease during hypoxia, hypercapnia, or following exhaustive exercise. Tuna physiology and behavior dictate exceptionally high rates of O2 delivery to the tissues often under adverse conditions, but especially during recovery from exhaustive exercise when plasma pH may be reduced by as much as 0.4 pH units. We hypothesize that blood O2 transport during periods of metabolic acidosis could be especially critical in tunas and the response of rbc to catecholamines elevated to an extreme. We therefore investigated the in vitro response of red blood cells from yellowfin tuna (Thunnus albacares) and skipjack tuna (Katsuwonus pelamis) to catecholamines. Tuna red blood cells had a typical response to catecholamines, indicated by a rapid decrease in plasma pH. Amiloride reduced the response, whereas 4,4'diisothiocyanatostilbene-2,2'-disulphonic acid enhanced both the decrease in plasma pH and the increase in intracellular pH. Changes in plasma [Na+], [Cl-], and [K+] were consistent with the hypothesis that tuna red blood cells have a Na+/H+ antiporter similar to that described for other teleost red blood cells. Red blood cells from both tuna species were more responsive to noradrenaline than adrenaline. At identical catecholamine concentrations, the decrease in plasma pH was greater in skipjack tuna blood, the more active of the two tuna species. Based on changes in plasma pH, the response of red blood cells to catecholamines from both tuna species was less than that of rainbow trout (Oncorhynchus mykiss) red blood cells, but greater than that of cod (Gadus morhua) red blood cells. Noradrenaline had no measurable influence on the O2 affinity of skipjack tuna blood and only slightly increased the O2 affinity of yellowfin tuna blood. Our results, therefore, do not support our original hypothesis. The catecholamine response of red blood cells from high-energy-demand teleosts (i.e., tunas) is not enhanced compared to other teleosts. There are data on changes in cardio-respiratory function in tunas caused by acute hypoxia and modest increases in activity, but there are no data on the changes in cardio-respiratory function in tunas accompanying the large increases in metabolic rate seen during recovery from exhaustive exercise. However, we conclude that during those instances where high rates of O2 delivery to the tissues are needed, tunas' ability to increase cardiac output, ventilation volume, blood O2 carrying capacity, and effective respiratory (i.e., gill) surface area are probably more important than are the responses of red blood cells to catecholamines. We also use our data to investigate the extent of the Haldane effect and its relationship to blood O2 and CO2 transport in yellowfin tuna. Yellowfin tuna blood shows a large Haldane effect; intracellular pH increases 0.20 units during oxygenation. The largest change in intracellular pH occurs between 40-100% O2 saturation, indicating that yellowfin tuna, like other teleosts, fully exploit the Haldane effect over the normal physiological range of blood O2 saturation.     

Effect of physical training on exercise-induced hyperkalemia in chronic heart failure. Relation with ventilation and catecholamines

BACKGROUND: The exercise-induced rise in arterial potassium concentration ([K+]a) may contribute to exercise hyperpnea and could play a role in exertional fatigue. This study was designed to determine whether the exercise-induced rise in [K+]a is altered in patients with chronic heart failure (CHF) and whether physical training affects K+ homeostasis. METHODS AND RESULTS: We evaluated 10 subjects with CHF (ejection fraction, 23 +/- 3.9%) and 10 subjects with normal left ventricular function (NLVF) who had undergone previous coronary artery graft surgery (ejection fraction, 63 +/- 8.6%). Subjects performed an incremental cycle ergometer exercise test before and after a physical training or detraining program. Changes in [K+]a and ventilation (VE) during exercise were closely related in both groups. Subjects with CHF did less absolute work and had reduced maximal oxygen consumption (VO2max) compared with subjects with NLVF (P < .01). Exercise-induced rises in [K+]a, VE, norepinephrine, lactate, and heart rate were greater at matched absolute work rates in subjects with CHF than in subjects with NLVF (P < .01). However, when the rise in [K+]a was plotted against percentage of VO2max to match for relative submaximal effort, there were no differences between the two groups. Physical training resulted in reduced exercise-induced hyperkalemia at matched submaximal work rates in both groups (P < .01) despite no associated change in the concentration of arterial catecholamines. At maximal exercise when trained, peak increases in [K+]a were unaltered, but peak concentrations of catecholamines were raised (P < .05). The decrease in VE at submaximal work rates after training was not significant with this incremental exercise protocol, but both groups had an increased peak VE when trained (P < .01). CONCLUSIONS: Exercise-induced rises in [K+]a, catecholamines, and VE are greater at submaximal work rates in subjects with CHF than in subjects with NLVF. Physical training reduces the exercise-induced rise in [K+]a but does not significantly decrease VE during submaximal exercise with this incremental cycle ergometry protocol. The reduction in exercise-induced hyperkalemia after training is not the result of altered concentrations of arterial catecholamines. The pathophysiological significance of the increased exercise-induced hyperkalemia in CHF and the mechanisms of improved K+ homeostasis with training have yet to be established.     

Threshold increases in plasma growth hormone in relation to plasma catecholamine and blood lactate concentrations during progressive exercise in endurance-trained athletes

Plasma human growth hormone ([HGH]), adrenaline ([A]), noradrenaline ([NA]) and blood lactate ([La-](b)) concentrations were measured during progressive, multistage exercise on a cycle ergometer in 12 endurance-trained athletes [aged 32.0 (SEM 2.0) years]. Exercise intensities (3 min each) were increased by 50 W until the subjects felt exhausted. Venous blood samples were taken after each intensity. The [HGH] and catecholamine concentrations increased negligibly during exercise of low to moderate intensities revealing an abrupt rise at the load corresponding to the lactate threshold ([La-]-T). Close correlations (P <0.001) were found between [La-]b and plasma [HGH] (r = 0.64), [A] (r = 0.71) and [NA] (r = 0.81). The mean threshold exercise intensities for [HGH], [A] and [NA], detected by log-log transformation, [154 (SEM 19) W, 162 (SEM 15) W and 160 (SEM 17) W, respectively] were not significantly different from the [La-]-T [161 (SEM 12) W]. The results indicated that the threshold rise in plasma [HGH] followed the patterns of plasma catecholamine and blood lactate accumulation during progressive exercise in the endurance-trained athletes.     

Augmented exercise plasma noradrenaline with impaired chronotropic responsiveness in patients with hypertrophic cardiomyopathy

1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients with HCM. 2. Plasma noradrenaline (NA) and adrenaline were measured at rest, at the end of each stage during exercise and immediately and 5 min after submaximal treadmill exercise in 15 patients with non-obstructive HCM (13 males, two females; mean (+/- SEM) age 54 +/- 3 years) and in 15 age- and sex-matched controls. The ratio of the increment in heart rate (HR) divided by the increment in plasma NA during exercise (delta HR/delta NA) was used as an index of chronotropic sympathetic responsiveness to exercise. 3. Exercise duration was shorter (11.2 +/- 0.6 vs 8.7 +/- 0.6 min for control vs HCM, respectively; P < 0.01) and diastolic blood pressure was significantly higher at stages I and II of modified Bruce protocol HCM. 4. Resting plasma NA levels (149 +/- 17 vs 167 +/- 28 pg/mL for control vs HCM, respectively; NS) were not different, but plasma NA levels at stages I and II were significantly higher in HCM than in controls (243 +/- 26 vs 399 +/- 69 pg/mL (P < 0.05) and 308 +/- 30 vs 548 +/- 110 pg/mL (P < 0.05), respectively). 5. Peak plasma NA levels were not significantly higher in HCM than in controls (578 +/- 59 vs 918 +/- 184 pg/mL, respectively; NS). 6. The ratio delta HR/delta NA was significantly lower in HCM compared with control at stages I and II (0.49 +/- 0.10 vs 0.21 +/- 0.05 (P < 0.05) and 0.38 +/- 0.06 vs 0.20 +/- 0.05 (P < 0.05), respectively). There were no differences in plasma adrenaline responses during exercise between the two groups. 7. Patients with HCM had augmented plasma NA levels during submaximal exercise with a higher diastolic blood pressure response. Chronotropic sympathetic responsiveness was impaired during the early stages of exercise in patients with HCM.     

Lung diffusing capacity and exercise in subjects with previous high altitude pulmonary oedema

Subjects with a history of high-altitude pulmonary oedema (HAPE) have increased pulmonary artery pressure and more ventilation-perfusion (V'A/Q') inhomogeneity with hypoxia and exercise. We used noninvasive methods to determine whether there are differences in the pulmonary diffusing capacity for carbon monoxide (DL,CO) and cardiac output (Q') during exercise, indicative of a more restricted pulmonary vascular bed in subjects with a history of HAPE. Eight subjects with radiographically documented HAPE and five controls with good altitude tolerance had standard pulmonary function testing and were studied during exercise at 30 and 50% of normoxic maximal oxygen consumption (V'O2) at an inspiratory oxygen fraction of 0.14 and 0.21. DL,CO and Q' were measured by CO and acetylene rebreathing techniques. HAPE-resistant subjects had 35% greater functional residual capacity than HAPE-susceptible subjects. Vital capacity and total lung capacity were also 7-10% greater. There were no differences in airflow rates or resting diffusing capacity. However, DL,CO in HAPE-susceptible subjects was lower in hypoxia and with exercise, and showed less increase (32 versus 49%) with the combined stimulus of hypoxic exercise. HAPE-susceptible subjects had smaller increases in stroke volume, Q', and ventilation during exercise. The findings are consistent with lower pulmonary vasoconstriction, greater vascular capacitance and greater ventilatory responsiveness during exercise in subjects who are resistant to high-altitude pulmonary oedema. Their larger lung volumes suggest a constitutional difference in pulmonary parenchyma or vasculature, which may be a determinant of high-altitude pulmonary oedema resistance.     

Smaller lungs in women affect exercise hyperpnea

We subjected 29 healthy young women (age: 27 +/- 1 yr) with a wide range of fitness levels [maximal oxygen uptake (VO2 max): 57 +/- 6 ml . kg-1 . min-1; 35-70 ml . kg-1 . min-1] to a progressive treadmill running test. Our subjects had significantly smaller lung volumes and lower maximal expiratory flow rates, irrespective of fitness level, compared with predicted values for age- and height-matched men. The higher maximal workload in highly fit (VO2 max > 57 ml . kg-1 . min-1, n = 14) vs. less-fit (VO2 max < 56 ml . kg-1 . min-1, n = 15) women caused a higher maximal ventilation (VE) with increased tidal volume (VT) and breathing frequency (fb) at comparable maximal VT/vital capacity (VC). More expiratory flow limitation (EFL; 22 +/- 4% of VT) was also observed during heavy exercise in highly fit vs. less-fit women, causing higher end-expiratory and end-inspiratory lung volumes and greater usage of their maximum available ventilatory reserves. HeO2 (79% He-21% O2) vs. room air exercise trials were compared (with screens added to equalize external apparatus resistance). HeO2 increased maximal expiratory flow rates (20-38%) throughout the range of VC, which significantly reduced EFL during heavy exercise. When EFL was reduced with HeO2, VT, fb, and VE (+16 +/- 2 l/min) were significantly increased during maximal exercise. However, in the absence of EFL (during room air exercise), HeO2 had no effect on VE. We conclude that smaller lung volumes and maximal flow rates for women in general, and especially highly fit women, caused increased prevalence of EFL during heavy exercise, a relative hyperinflation, an increased reliance on fb, and a greater encroachment on the ventilatory "reserve." Consequently, VT and VE are mechanically constrained during maximal exercise in many fit women because the demand for high expiratory flow rates encroaches on the airways' maximum flow-volume envelope.