Effect of acetazolamide on sodium and potassium absorption in the sheep forestomach

The purpose of the present study was to determine whether the linear relationship between CO2 output (VCO2) and pulmonary ventilation (VE) is altered during incremental cycling performed after exercise-induced metabolic acidosis. Ten untrained, female subjects performed two incremental cycling tests (15 W x min(-1) up to 165 W) on separate days. One incremental exercise test was conducted without prior exercise, whereas the other test was preceded by a 1-min bout of maximal cycling. The ventilatory equivalent for O2 (VE/VO2) was only elevated above control values at 15-60 W during incremental cycling performed after high-intensity exercise. In contrast, the ventilatory equivalent for CO2 (VE/VCO2) was significantly increased above control levels at nearly every work stage of incremental work (all except 165 W). Hyperventilation relative to VCO2 was confirmed by the significantly lower end-tidal CO2 tension (P(ET)CO2) obtained throughout the incremental cycling that was performed after high-intensity exercise (except at 165 W). VE and VCO2 were significantly correlated under both treatment conditions (r > 0.99; P < 0.001). Moreover, both the slope and y-intercept of the linear regression were found to be significantly elevated during the incremental cycling performed after high-intensity cycling compared to control conditions (P < 0.01). The increase in the slope of the VE-VCO2 relationship during incremental exercise performed under these conditions does not represent an uncoupling of VE from VCO2, but could be accounted for by the significantly lower P(ET)CO2 observed during exercise.     

Assessment of fitness in patients with cystic fibrosis and mild lung disease

The purpose of this investigation was to examine if exercise-induced arterial oxyhemoglobin desaturation selectively observed in highly trained endurance athletes could be related to differences in the pulmonary diffusing capacity (DL) measured during exercise. The DL of 24 male endurance athletes was measured using a 3-s breath-hold carbon monoxide procedure (to give DLCO) at rest as well as during cycling at 60% and 90% of these previously determined VO2max. Oxyhemoglobin saturation (SaO2%) was monitored throughout both exercise protocols using an Ohmeda Biox II oximeter. Exercise-induced oxyhemoglobin desaturation (DS) (SaO2% < 91% at VO2max) was observed in 13 subjects [88.2 (0.6)%] but not in the other 11 nondesaturation subjects [NDS: 92.9 (0.4)%] (P < or = 0.05), although VO2max was not significantly different between the groups [DS: 4.34 (0.65) l/min vs NDS: 4.1 (0.49) l/min]. At rest, no differences in either DLCO [ml CO.mmHg-1.min-1: 41.7 (1.7) (DS) vs 41.1 (1.8) (NDS)], DLCO/VA [8.2 (0.4) (DS) vs 7.3 (0.9) (NDS)], MVV [l/min: 196.0 (10.4) (DS) vs 182.0 (9.9) (NDS)] or FEV1/FVC [86.3 (2.2) (DS) vs 82.9 (4.7) (NDS)] were found between groups (P > or = 0.05). However, VE/VO2 at VO2max was lower in the DS group [33.0 (1.1)] compared to the NDS group [36.8 (1.5)] (P < or = 0.05). Exercise DLCO (ml CO.mmHg-1.min-1) was not different between groups at either 60% VO2max [DS: 55.1 (1.4) vs NDS: 57.2 (2.1)] or at 90% VO2max [DS: 61.0 (1.8) vs NDS: 61.4 (2.9)]. A significant relationship (r = 0.698) was calculated to occur between SaO2% and VE/VO2 during maximal exercise. The present findings indicate that the exercise-induced oxyhemoglobin desaturation seen during submaximal and near-maximal exercise is not related to differences in DL, although during maximal exercise SaO2 may be limited by a relatively lower exercise ventilation.     

Normalization of acquired QT prolongation in humans by intravenous potassium

BACKGROUND: QT interval prolongation and dispersion have been implicated in serious arrhythmias in congestive heart failure (CHF) and the congenital and drug-induced long-QT syndromes (LQTS). In a subset of the congenital LQTS, infusion of potassium can correct QT abnormalities, consistent with in vitro increases in outward currents such as I(Kr) or I(Kl) when extracellular potassium concentration ([K+]o) is increased. Furthermore, increasing [K+]o decreases the potency of I(Kr)-blocking drugs in vitro. The purpose of this study was to test the hypothesis that increasing [K+]o corrects QT abnormalities in CHF and in subjects treated with quinidine. METHODS AND RESULTS: KCl (maximum, 40 mEq) was infused into (1) 12 healthy subjects treated with quinidine sulfate (5 doses of 300 mg/5 h) or placebo and (2) 8 CHF patients and age-matched normal control subjects. Mean [K+] increased from 4 to 4.2 mEq/L to 4.7 to 5.2 mEq/L. Potassium infusion significantly reversed QTUc prolongation, especially in the precordial leads (quinidine, 590+/-79 to 479+/-35 [+/-SD] ms(1/2), P<.001; CHF, 521+/-110 to 431+/-47 ms(1/2), P<.05). There was no effect in either control group. Similarly, potassium decreased QTUc dispersion (quinidine, 210+/-62 to 130+/-75 ms(1/2), P<.01; CHF, 132+/-68 to 84+/-35 ms(1/2), P=.07) and was without effect in the control subjects. QT morphological abnormalities, including U waves and bifid T waves, were reversed by potassium. CONCLUSIONS: Potentially arrhythmogenic QT abnormalities during quinidine treatment and in CHF can be nearly normalized by modest elevation of serum potassium.     

On the genetics of hypodontia and microdontia: synergism or allelism of major genes in a family with six affected members

Plasma beta-endorphin (beta-E) concentration was determined before, during, and after a standardized incremental exercise test to maximal capacity in eight type I diabetic patients and eight normal control subjects. Diabetic patients were studied under normoglycemic and hyperglycemic conditions in a single-blind random fashion to differentiate between the effects of acute hyperglycemia and of diabetes per se on the beta-E response to exercise. The perceived magnitude of leg effort elicited by exercise was evaluated using a category scale. Whereas plasma beta-E concentrations increased in control subjects with increasing workload, causing significantly higher beta-E levels at the end of exercise than at the beginning (P < .001), no such increase could be observed in the diabetic patients under normoglycemic and hyperglycemic conditions. In addition, baseline plasma beta-E concentrations were significantly lower in normoglycemic (P < .01) and hyperglycemic (P < .001) diabetic patients than in control subjects. Even during the recovery period, patients' beta-E levels remained significantly lower than those of control subjects. At submaximal levels of power output, the perceived intensity of leg effort was significantly higher in normoglycemic and hyperglycemic diabetic patients than in control subjects. We conclude that in type I diabetic patients, the ability of the endogenous opioid system to respond to exercise-induced stress is impaired under hyperglycemic and even under normoglycemic conditions. Considering the effect of endogenous opioids on stress tolerance, such changes may compromise exercise performance in diabetic patients.     

Muscle oxygenation kinetics measured by near-infrared spectroscopy during recovery from exercise in chronic heart failure

The aim of the present study was to determine the kinetics of recovery of muscle oxygenation (MO) from comparable levels of exercise in chronic heart failure (CHF) patients and normal subjects and to relate MO kinetics to the level of exercise intolerance. The rationale is based on the observation that the O2 debt is increased in patients with heart failure and repayment of the debt is relatively slow. Ten patients with stable CHF (mean age 47 +/- 10 years) and nine healthy control subjects (47 +/- 6 years) were studied. All patients had ischemic cardiomyopathy (ejection fraction 33 +/- 7%). On different days, all subjects performed an upright incremental cycle ergometer exercise test with gas-exchange analysis to determine peak VO2, and a 6-minute constant work-rate (CWR) protocol at 60% of peak VO2. Oxygenation of the vastus lateralis muscle was continuously monitored during exercise and recovery using near-infrared spectroscopy (NIRS). Both MO and VO2 responses to recovery were described by a monoexponential model with a time delay. The time constant and time delay were combined to calculate a mean response time (MRT). Recovery VO2 and MO MRTs for the incremental and constant work rate exercise test were longer in CHF patients than in control subjects (p < 0.05). Both VO2 and MO MRTs were inversely related to peak VO2 (r = -0.73 and -0.52, respectively; p < 0.05 for both). However, both kinetics were not significantly different within each group between the two exercise intensities. In conclusion, the greater the cardiac dysfunction, as assessed by peak VO2, the more the recovery of muscle and total body oxygenation from both maximal and submaximal exercise is delayed.     

Anthropometric determination of thigh volumes and thigh forces following acute training of increasing intensity in adult men

The purpose of the present study was to investigate the influence of submaximal training of increasing intensity on the rate of fatigue and on the anthropometry of the quadriceps muscle. A group of 24 middle-aged male subjects trained three times a week for 12 weeks at incremental exercise intensities which elicited 66%-83% of the maximal heart rate reserve; 11 male subjects acted as controls. A purpose-built, isometric chair with an adjustable force transducer ensured a standard posture for each subject during a 20 s maximal voluntary contraction (MVC). The muscle plus bone mass of the thigh was calculated from a previously validated anthropometric method reinforced by measurements derived from water displacement and ultrasonics. Training-induced submaximal relationships were assessed by means of two ergometer tests of progressive intensity. Following training, the subjects' blood lactate concentrations had decreased from 5.5 (SD 1.7) to 3.9 (SD 1.4) mmol.1(-1) (P < 0.01) at the final exercise intensities. They increased thigh volumes from 10.7 (SD 1.7) to 11.0 (SD 1.7) 1 (P < 0.05) and thigh forces in 47.5% (P < 0.05) of the measurements. Heart rates and rates of perceived exertion were reduced (P < 0.01) following training; for the controls, all the above parameters remained constant. These results would seem to indicate that a submaximal type of training could enable a group of middle-aged men to increase the isometric forces of the thigh muscles by almost 50% when completing a MVC test following training. This suggests that this is a more suitable, safer form of maintaining and increasing maximal thigh forces for this, and older, age groups than specific isometric training alone.     

Unaltered oxygen uptake kinetics at exercise onset with lower-body positive pressure in humans

The purpose of this study was to determine the influence of a reduced skeletal muscle blood flow on oxygen uptake (VO2) kinetics at the onset of cycle ergometer exercise. Seven healthy subjects performed rest-to-exercise transitions with a lower-body positive pressure (LBPP) of 45 Torr. Two work rates were selected for each subject: a moderate intensity (VO2, approximately 1.9 l min-1; delta[lactate], approximately 1 mequiv l-1) below the estimated lactate threshold and a heavy intensity (VO2, approximately 2.6 l min-1; delta[lactate], approximately 3 mequiv l-1) above this threshold. Pulmonary gas exchange variables and ventilatory (VE) responses were computed breath-by-breath from mass spectrometer and turbine volume meter signals, respectively, and mean response times (MRT) calculated. Samples of 'arterialized' venous blood were used for the determination of [lactate], pH and [K+]. While the application of 45 Torr LBPP had no effects on VO2 kinetics during moderate exercise (MRT: 33.5 +/- 1.2 s at 45 Torr vs. 32.8 +/- 1.3 s at 0 Torr; P > 0.05) or on [lactate], pH or [K+], breathing frequency (f) was increased (P < 0.05) and tidal volume (VT) reduced (P < 0.05). The addition of LBPP during heavy exercise did not alter VO2 kinetics (MRT: 35.2 +/- 1.5 s at 45 Torr vs. 34.8 +/- 1.5 s at 0 Torr; P > 0.05), or [lactate], pH or [K+]. Although both the VE (via an increased f) and CO2 output (VCO2) were significantly greater with LBPP by approximately 30 l min-1 and approximately 500 ml min-1, respectively, end-tidal CO2 partial pressure was decreasing, suggesting an additional ventilatory stimulus. These data can be interpreted to suggest that oxygen delivery is not critically dependent upon blood flow to the working muscle at exercise onset, while LBPP-induced increases in VE during suprathreshold exercise may be related to an accumulation of metabolites at the working muscle or the effects of pressure per se.     

Metoprolol abolishes exercise-induced left ventricular dysfunction in patients with silent ischemia

Left ventricular systolic function is reduced during episodes of silent ischemia in patients with coronary artery disease (CAD). Left ventricular ejection fraction (LVEF) is increased at least 5 absolute percent during exercise in most normal subjects; however, in patients with CAD, LVEF often remains unchanged or decreases. The anti-ischemic effect of beta-adrenergic receptor blockade is well documented, including a reduction of exercise-induced electrocardiographic ST depressions; however, the effect of these drugs on left ventricular volume changes during exercise in patients with silent ischemia is unknown. The aim of this study was to evaluate the effect of a cardio-selective beta-blocking agent, metoprolol, on rest and exercise LVEF in patients with silent ischemia, using radionuclide cardiography. Fifteen patients with silent ischemia completed a double-blind, placebo-controlled crossover study at rest and during submaximal exercise. LVEF remained unchanged during exercise in the placebo phase (56% to 58%; p = NS), but even though LVEF tended to decrease 56% during rest after metoprolol versus 52% after placebo (p = NS), the LVEF increase from rest to exercise resembled a normal LVEF response, 52% to 58% (p = 0.005). Exercise-induced electrocardiographic ST depressions were also reduced during metoprolol treatment. In patients with silent ischemia, the exercise-induced change in LVEF rises significantly during metoprolol treatment. The mechanism may be a reduction in myocardial ischemia as indicated by a reduction in ischemic electrocardiographic findings.     

Protection of residents in the vicinity of intensive livestock units from possible health risks

To assess whether hormone and metabolic responses in an upright bicycle exercise test are equivalent for subjects with different physical characteristics if test duration for reaching individual maximal work capacity (PWCmax) is standardized we investigated plasma catecholamines, human atrial natriuretic peptide (hANP) and blood lactate responses in twenty healthy sedentary subjects. Ten male (38.5 +/- 4.7 yrs) and ten female (34.5 +/- 6.4 yrs) healthy volunteers performed two ergometries, a first one with incremental steps of 25 Watts each for two minutes to determine PWCmax, and a second one with incremental steps of PWCmax/6. According to this definition a test duration of 12 min was attained for all subjects for the second ergometry. The results show that the increase of the rate pressure product (RPP) as an index of relative cardiac work is significantly different between the male and female group in the test with constant 25 Watts steps. But with the modified exercise test RPP/time-slopes are nearly identical, identicating equivalent cardiac work due to gender and body surface. Similar results are obtained for plasma catecholamines, hANP and blood lactate. Mean values did not differ in the modified exercise test between the male and female group either in the sub-maximal range or at PWCmax. In conclusion, our data suggest that in a maximal exercise test with equal test duration, and considering individual physical properties for the calculation of incremental steps hormonal and metabolic responses are equivalent. It seems that the designed, modified exercise test provides inter-individual comparisons at least for these investigated parameters. The test may be helpful if catecholamines, hANP or lactate are used as diagnostic parameters in patients.     

Gene transfer vectors derived from equine infectious anemia virus

OBJECTIVE: To determine the effects of acute exercise on hepatic blood flow by studying hepatic clearance of bromsulphalein for several submaximal exercise intensities. ANIMALS: 8 adult Standardbred mares. PROCEDURE: Horses were subjected to 4 submaximal exercise intensities (resting and 40, 60, and 80% maximal oxygen consumption). After horses had been running at the required treadmill speed for 1 minute, bromsulphalein (BSP; 5 mg/kg of body weight, IV) was administered during a 45- to 60-second period, and horses continued at the desired speed for an additional 15 minutes. Blood samples were collected at 2-minute intervals for 30 minutes, and plasma concentration of BSP was determined by spectrophotometry. Estimates of pharmacokinetic variables were compared among the 4 exercise intensities, using a Friedman repeated-measures analysis on ranks and linear regression. RESULTS: Median values for clearance of BSP from blood and plasma decreased significantly with exercise and was linearly related to exercise intensity. Exercise-induced differences were not detected in the volume of distribution of BSP. Elimination half-life of BSP increased significantly with increasing exercise intensity and was linearly related to exercise intensity. CONCLUSIONS: Acute submaximal exercise has a dramatic effect on clearance of BSP in horses. Presumably, exercise-induced decreases in splanchnic blood flow limit blood flow to the liver, decreasing hepatic clearance of BSP and leading to persistence of plasma concentrations of BSP. CLINICAL IMPLICATIONS: Drugs that are efficiently extracted by the liver may have decreased hepatic clearance when horses exercise at submaximal intensities.     

Reduced myocardial Na+, K(+)-pump capacity in congestive heart failure following myocardial infarction in rats

We examined changes in expression and function of the cardiac Na+, K(+)-pump in a post-infarction rat model of hypertrophy and congestive heart failure (CHF). Myocardial infarction was induced by ligation of the left coronary artery in Wistar rats and hearts were obtained from animals with CHF and from sham operated rats after 6 weeks. In the CHF group the ratio of heart weight to body weight was 70% greater compared to sham (*P < 0.05) and all left-ventricular end-diastolic pressures (LVEDP) were above 15 mmHg. The expression of the alpha 1- and beta 1-subunits (mRNA and protein) of the Na+, K(+)-pump was not significantly different in CHF and sham. As compared to sham the alpha 2 isoform, mRNA and protein levels were lower in CHF hearts by 25 and 55%, respectively, whereas the alpha 3 isoform mRNA was greater by 120% in CHF. The alpha 3 protein was not detectable in sham but a prominent band was seen in CHF. Cell volume of isolated cardiomyocytes was 30% larger in CHF. Cardiomyocytes containing the Na+ sensitive fluorescent dye SBFI were loaded to an intracellular Na+ concentration ([Na+]i] of about 140 mM in a K(+)- and Mg(2+)-free medium (140 mM Na+, free Ca2+ of 10(-8) M). To avoid back leak of Na+ and to ensure no voltage effects on the Na+, K(+)-pump extracellular Na+ was subsequently removed, and 6 mM Mg2+ was added to the superfusate, The Na+, K(+)-pump was then reactivated by 10 mM Rb+. SBFI fluorescence ratio decreased mono-exponentially with a time constant (tau) of 191 +/- 15 s in sham (n = 8) and 320 +/- 38 s in CHF (n = 9) rats (P < 0.01). These changes in fluorescence indicate that the maximum rate of decline of [Na+]i from 100 to 35 mM was 39% (P < 0.005) slower in CHF compared to sham, whereas maximum pump rate per cell was not significantly altered (9.0 +/- 0.7 fmol/s in sham and 7.1 +/- 0.7 fmol/s in CHF cells). The [Na+]i which caused 50% pump activation (k0.5) was also not altered in CHF (40 mM in both groups). We conclude that the number of Na+, K(+)-pumps per cell was maintained in CHF but an isoform switch of the alpha 3-replacing the alpha 2-isoform occurred. However, maximum Na+, K(+)-pump rate in terms of rate of change of [Na+]i was significantly attenuated in CHF, most likely as a result of increased cell size.     

Renal depressor mechanisms of physical training in patients with essential hypertension

To clarify characteristics of the patients in whom exercise training lowers blood pressure and to elucidate the mechanisms by which exercise training lowers blood pressure, we evaluated 24-h blood pressure, glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma norepinephrine concentration (PNE), and incremental area of insulin/glucose (sigmaI/sigmaG) during 75 g oral glucose tolerance test, and assessed arterial baroreceptor function (BSI) before and after a 3-week exercise training program (four 6-min sessions daily at 75% VO2 max). Patients were classified as responders (n = 15) if they showed statistically significant reduction in the multiple comparison of 24-h mean arterial pressure (MAP), or as nonresponders (n = 15) if they did not. Although there were no significant differences between responders and nonresponders in age, weight, MAP, GFR, RBF, RPF, FF, PNE, sigmaI/sigmaG, or BSI before exercise, renal vascular resistance (RVR; P < .05), PRA (P < .05), and PAC (P < .05) were significantly higher in responders than in nonresponders. The fractional excretion of sodium (FENa) (P < .05) were significantly lower in responders than in nonresponders. After exercise training, FF (P < .01), RVR (P < .05), PNE (P < .05) PRA (P < .01), and sigmaI/sigmaG (P < .05) decreased significantly only in responders. The decrease in MAP significantly correlated with the reductions in FF (r = 0.46, P < .05), PNE (r = 0.52, P < .01) and RVR (r = 0.40, P < .05). Thus, in patients who have higher RVR and PRA, exercise training lowered blood pressure in parallel to a reduction in RVR associated with decreases in sympathetic tone and improvement of insulin resistance. Our results suggest that exercise-induced changes in renal hemodynamics may contribute to the reduction in blood pressure in these patients.     

Changes in gas exchange kinetics with training in patients with spinal cord injury

We examined the ability of patients with spinal cord injury to undergo adaptations to chronic exercise training (cycle ergometry) invoked by functional electrical stimulation (FES) of the legs. Nine such patients performed incremental and constant work rate exercise before and after exercise training. Exercise sessions averaged 2.1 +/- 0.4/wk, and consisted of 30 min/session of continuous FES recumbent cycling with increasing work rate as tolerated. Peak VO2 and peak work rate significantly improved with training. Peak VO2 was significantly correlated with peak heart rate both before and after training (r = 0.97 pre and 0.85 post, P < 0.01 for both). The time course of the VO2, VCO2 and VE responses to constant-load exercise (unloaded cycling) and in recovery (mean response time MRT) were very long prior to training, and became significantly faster following training. However, there was no correlation between percentage improvement in either MRTon or MRToff for VO2 and the percentage increase in peak VO2. Exercise tolerance in these patients with spinal cord injury appears to be a direct function of the ability to increase heart rate. Further, exercise training can elicit significant improvements in both exercise tolerance and in gas exchange kinetics, even when performed only twice per week. However, these improvements may be accomplished by different mechanisms.     

Skeletal muscle fiber type, resistance training, and strength-related performance

The research goal was to attempt to clarify the consequences of increased strength on performance at submaximal exercise intensities. Eight subjects (4 males, 4 females) completed a 3-d.wk-1, 16-wk resistance training regimen. After training, upper (bench press, BP) and lower (parallel squat, PS) extremity strength were increased by 23% and 37%, respectively. Performance at the same absolute work rates as before training was increased by 30-159% following training depending on intensity and type of exercise. Performance at the same relative work rates (80%, 60%, 40%) remained unchanged by the training for both exercises. Prior to training, PS repetitions at 40% were correlated (r = 0.69, P < 0.05) with the percentage of slow-twitch (ST) fibers in the vastus lateralis muscle. There were similar relationships at 40% (r = 0.73) and at 60% (r = 0.83) for the PS exercise after training. However, the resistance program did not result in greater relative submaximal performance in individuals with a higher percentage of ST fibers. We conclude that strength improvement of up to 40% does not produce a strength-related performance deficit, when training and testing procedures are identical. Yet, these data do not rule out the potential of a strength-related repetition performance deficit. When subjects were equally divided by strength levels, those tested at the highest absolute resistance had significantly lower bench press repetition performance at 60% and 40% of the 1-RM than the subjects tested at the lowest absolute resistance.     

Effect of acute bicarbonate administration on exercise responses of COPD patients

Patients with severe chronic obstructive pulmonary disease (COPD) are limited in their exercise tolerance by the level of ventilation (VE) they can sustain. We determined whether acutely increasing blood bicarbonate levels decreased acid stimulation to the respiratory chemoreceptors during exercise, thereby improving exercise tolerance. Responses were compared with those obtained during 100% O2 breathing (known to reduce VE in these patients) and to the responses of healthy young subjects. Participants were six patients with severe COPD (forced expired volume in 1 s = 31 +/- 11% predicted) but without chronic CO2 retention and 5 healthy young subjects. Each subject performed three incremental cycle ergometer exercise tests: 1) control, 2) after ingestion of 0.3 g.kg-1 of sodium bicarbonate and 3) while breathing 100% O2. During these tests VE was measured continuously and arterialized venous blood (patients) or arterial blood (healthy subjects) was sampled serially to assess acid base variables. Bicarbonate loading increased standard bicarbonate by 4-6 mmol.L-1 and this elevation persisted during exercise. In both groups, bicarbonate loading resulted in a substantially higher arterial pH; arterial PCO2 was either unchanged (healthy subjects) or mildly (averaging 5 torr) higher (COPD patients). However, in neither group did bicarbonate loading result in an altered VE response to exercise or an increase in exercise tolerance. In contrast, superimposing hyperoxia on bicarbonate ingestion yielded, on average, 24% reduction in VE and 50% increase in peak work rate in the patients (but not in the healthy young subjects). We conclude that acute bicarbonate loading is not an ergogenic aid in patients with severe COPD.     

The kinetics of extracellular potassium changes during hypoxia and anoxia in the cat cerebral cortex

Extracellular potassium activity, [K+]0, was continuously measured using potassium specific microelectrodes in the cerebral cortex of cats before and after hypoxic or anoxic insults. Two patterns of [K+]0 increase were seen. A slow, linear rise occurred during hypoxia and hypothermia and was correlated with changes in mean blood pressure (B/P). A fast, complex, exponential rise resembling spreading depression occurred during anoxia and was unassociated with B/P changes. The fall of [K+]0 after reversal of the insult was described by a single exponential function with rate constants from 0.009 to 0.0194 sec-1. It is suggested that the linear rise is primarily a result of sodium pump inhibition and that the exponential rise is due to a superimposed sudden increase in cell membrane permeability perhaps secondary to transmitter release. The kinetics of the fall of [K+[0 is consistent with the normalization of the sodium and potassium gradients across the cell membranes secondary to Na+-K+ATPase activity.     

Exercise responses in patients with IDDM

OBJECTIVE: The hemodynamic, respiratory, and metabolic responses to exercise were studied in IDDM patients and control subjects to detect diabetic cardiomyopathy. RESEARCH DESIGN AND METHODS: Eight subjects aged 25-40 years with diabetes of at least 10 years' duration were compared with eight control subjects aged 21-46 years. All subjects underwent a progressive incremental bicycle exercise test with measurement of gas exchange, blood glucose, lactate, fat metabolite, and catecholamine levels and two steady-state exercise tests with measurement of cardiac output by a CO2 rebreathing method. A new first-pass radionuclide method was used to measure cardiac ejection fractions (EFs) at rest, peak exercise, and steady-state exercise. RESULTS: The peak achieved oxygen consumption was similar in the diabetic and control subjects (29.9 [25.1-34.6] and 31.4 [26.9-35.9] ml.min-1.kg-1, respectively; mean [95% CI]). There were no significant differences in heart rate, double product, ventilation, respiratory exchange ratio, or ventilatory equivalents for oxygen and CO2 during the incremental test. Glucose levels were higher in the diabetic subjects, but there were no significant differences in levels of lactate, catecholamines, free fatty acids, glycerol, or beta-hydroxybutyrate. Left ventricular EF fell from rest to peak exercise within the diabetic group (66.0% [59.6-72.4] at rest; 53.6% [45.6-61.6] at peak; P < 0.05) but this did not differ significantly from the control group (58.7% [52.3-65.1] at rest; 60.3% [48.9-71.7] at peak). Right ventricular EFs were similar in each group, and there was no reduction in peak filling rate to suggest diastolic dysfunction. The cardiac output responses to exercise were also similar in the two groups. CONCLUSIONS: There is no evidence of impairment of the exercise response in subjects with long-standing diabetes, and the apparent fall in left ventricular EF at peak exercise could be related to hemodynamic adaptation.     

Effect of systemic versus topical nonsteroidal anti-inflammatory drugs on postexercise jaw-muscle soreness: a placebo-controlled study

Certain types of jaw-muscle pain may be managed with pharmacologic treatment. This study evaluated the effect of topical and systemic nonsteroidal anti-inflammatory drugs on acute postexercise jaw-muscle soreness. Ten men without temporomandibular disorders performed six 5-minute bouts of submaximal eccentric jaw exercise. The outcome variables were pressure pain thresholds and pain tolerance thresholds at the masseter muscles, and maximum voluntary occlusal force. Surface electromyography from the masseter muscles was used to assess the development of muscle fatigue during the exercise period. Three treatment modalities were tested in a placebo-controlled, double-blind approach: (A) placebo gel and placebo tablets; (B) nonsteroidal anti-inflammatory drug gel (2 g, 5% ibuprofen) and placebo tablets; and (C) placebo gel and nonsteroidal anti-inflammatory drug tablets (400 mg ibuprofen). The subjects used their medication 3 times a day for 3 days in the postexercise period. In the exercise period, the mean power frequency of the electromyography signal, pressure pain threshold, pain tolerance threshold, and maximum voluntary occlusal force decreased significantly (analysis of variance, P < .01). In the postexercise period, the effect of treatment on pressure pain thresholds was significant (F[2,9] = 4.41, P = .02). On day 3, treatment with topical nonsteroidal anti-inflammatory drugs was associated with significantly higher pressure pain thresholds as compared to treatment with systemic nonsteroidal anti-inflammatory drugs (P < .05) and placebo (P < .05). Treatment effects on pain tolerance thresholds and on maximum voluntary occlusal force were nonsignificant. The results demonstrated that repeated eccentric jaw exercise caused muscle fatigue and low levels of postexercise pain and soreness. Topical nonsteroidal anti-inflammatory drugs seem to have some advantages over systemic nonsteroidal anti-inflammatory drugs for management of exercise-induced jaw-muscle pain.     

Metabolic and hemodynamic responses of lower limb during exercise in patients with COPD

Premature lactic acidosis during exercise in patients with chronic obstructive pulmonary disease (COPD) may play a role in exercise intolerance. In this study, we evaluated whether the early exercise-induced lactic acidosis in these individuals can be explained by changes in peripheral O2 delivery (O2). Measurements of leg blood flow by thermodilution and of arterial and femoral venous blood gases, pH, and lactate were obtained during a standard incremental exercise test to capacity in eight patients with severe COPD and in eight age-matched controls. No significant difference was found between the two groups in leg blood flow at rest or during exercise at the same power outputs. Blood lactate concentrations and lactate release from the lower limb were greater in COPD patients at all submaximal exercise levels (all P < 0.05). Leg D02 at a given power output was not significantly different between the two groups, and no significant correlation was found between this parameter and blood lactate concentrations. COPD patients had lower arterial and venous pH at submaximal exercise, and there was a significant positive correlation between venous pH at 40 W and the peak O2 uptake (r = 0.91, P < 0.0001). The correlation between venous pH and peak O2 uptake suggests that early muscle acidosis may be involved in early exercise termination in COPD patients. The early lactate release from the lower limb during exercise could not be accounted for by changes in peripheral O2. The present results point to skeletal muscle dysfunction as being responsible for the early onset of lactic acidosis in COPD.     

Effect of step duration during incremental exercise on breathing pattern and mouth occlusion pressure

We compared the effects of two step durations on breathing pattern, mouth occlusion pressure and "effective" impedance of the respiratory system during incremental exercise. Nine normal subjects (mean age: 27.8+/-1.21 years) performed two incremental exercise tests in randomized order: one test with step increments every 1 min 30s and the other, every 4 min. After a warm-up at 25 W for the 1 min 30 s test, the power was increased by 50 W from 50 W to exhaustion. During the last minute at each power, we measured ventilation (VE), tidal volume (VT), breathing frequency (fR), inspiratory and expiratory time (TI and TE), total time of the respiratory cycle (TTOT), TI/TTOT, mean inspiratory flow (VT/TI), mouth occlusion pressure (P0.1), "effective" impedance of the respiratory system (P0.1/(VT/ TI)) and venous blood lactate concentration ([La]). Our result showed that at maximal exercise the power was significantly higher (p < 0.01) and [La] lower (p < 0.01) in the 1 min 30 s test. At 100, 150 and 200 W, the 4 min test showed significantly higher oxygen uptake (VO2), carbon dioxide output (VCO2), VE, P0.1, fR, VT/TI and HR (p <0.001) and significantly lower TI, TE and TTOT (p<0.01). [La] was significantly higher at 150 W (p<0.05) and 200 W (p<0.001). At the same VCO2, P0.1 was not significantly different between the two tests, whereas VE showed a tendency to be higher (p = 0.08) and P0.1/(VT/TI) was significantly lower during the 4 min test. In conclusion, this study allowed us to quantify the difference in inspiratory neuromuscular output and ventilatory response between 1 min 30s and 4 min tests and showed that different step durations alter the relationship between inspiratory neuromuscular output and mean inspiratory flow.