Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites.

Exercise is an efficient strategy for myocardial protection against ischemia-reperfusion (IR) injury. Although endothelial nitric oxide synthase (eNOS) is phosphorylated and activated during exercise, its role in exercise-induced cardioprotection remains unknown. This study investigated whether modulation of eNOS activation during IR could participate in the exercise-induced cardioprotection against IR injury. Hearts isolated from sedentary or exercised rats (5 weeks training) were perfused with a Langendorff apparatus and IR performed in the presence or absence of NOS inhibitors [N-nitro-L-arginine methyl ester, L-NAME or N5-(1-iminoethyl)-L-ornithine, L-NIO] or tetrahydrobiopterin (BH4). Exercise training protected hearts against IR injury and this effect was abolished by L-NAME or by L-NIO treatment, indicating that exercise-induced cardioprotection is eNOS dependent. However, a strong reduction of eNOS phosphorylation at Ser1177 (eNOS-PSer1177) and of eNOS coupling during early reperfusion was observed in hearts from exercised rats (which showed higher eNOS-PSer1177 and eNOS dimerization at baseline) in comparison to sedentary rats. Despite eNOS uncoupling, exercised hearts had more S-nitrosylated proteins after early reperfusion and also less nitro-oxidative stress, indexed by lower malondialdehyde content and protein nitrotyrosination compared to sedentary hearts. Moreover, in exercised hearts, stabilization of eNOS dimers by BH4 treatment increased nitro-oxidative stress and then abolished the exercise-induced cardioprotection, indicating that eNOS uncoupling during IR is required for exercise-induced myocardial cardioprotection. Based on these results, we hypothesize that in the hearts of exercised animals, eNOS uncoupling associated with the improved myocardial antioxidant capacity prevents excessive NO synthesis and limits the reaction between NO and O2·- to form peroxynitrite (ONOO⁻), which is cytotoxic.

Vascular reactivity at rest and during exercise in middle-aged obese men: effects of short-term, low-intensity, exercise training.

OBJECTIVE: Although increased blood flow (BF) in exercising muscles is thought to be impaired in obese subjects and may contribute to physical inactivity, data are scarce in this regard and the involvement of endothelium dysfunction remains partly hypothetical. METHODS: A total of 16 middle-aged obese men (body mass index, BMI ≥ 30 kg m(-2)) and 16 normal-weight men (BMI<25 kg m(-2)), matched for age, were recruited. We used ultrasonography to compare intima-media thickness (IMT) and distensibility of the carotid artery, flow-mediated dilation (FMD), nitrate-dependent dilation (NDD) and peak BF during post-ischemic hyperemia in the brachial artery (a conduit artery), and leg BF during knee-extensor exercise (indicative of resistance vessel function) in obese and in normal-weight men. In addition, 10 obese men participated in an 8 week individualized low-intensity training program. RESULTS: Compared with normal-weight men, obese men had higher carotid IMT (0.50 ± 0.01 vs 0.62 ± 0.04 mm, P < 0.05) but lower carotid distensibility (0.26 ± 0.03 vs 0.11 ± 0.03 mm Hg(-1) 10(-2), P < 0.05), FMD (5.7 ± 0.4 vs 3.3 ± 0.5%, P < 0.05) and peak BF during post-ischemic hyperemia (398 ± 52 vs 229 ± 24%, P < 0.05), despite similar maximal shear rate, without NDD differences. Lower limb BF (ml min(-1) 100 g(-1)) increased significantly from rest to maximal exercise in both groups with lower values in obese men (at peak power, 36.9 ± 1.6 vs 31.5+2.2 ml min(-1) 100 g(-1), P < 0.05). Exercise training normalized carotid distensibility (0.14 ± 0.04 before vs 0.23 ± 0.03 mm Hg(-1) 10(-2) after training, P = 0.09) and FMD (2.7 ± 0.4 before vs 4.8 ± 0.5% after training, P < 0.05), but did not improve brachial post-ischemic peak BF or exercising leg BF. CONCLUSIONS: In obese men, conduit and resistance vessel reactivity is depressed, but a short-term low-intensity exercise training improves distensibility and endothelium dependent vasodilation in the large conduit artery, but not post ischemic or exercise muscle BF.

Simulated urban carbon monoxide air pollution exacerbates rat heart ischemia-reperfusion injury.

Myocardial damages due to ischemia-reperfusion (I/R) are recognized to be the result of a complex interplay between genetic and environmental factors. Epidemiological studies suggested that, among environmental factors, carbon monoxide (CO) urban pollution can be linked to cardiac diseases and mortality. The aim of this work was to evaluate the impact of exposure to CO pollution on cardiac sensitivity to I/R. Regional myocardial I/R was performed on isolated perfused hearts from rats exposed for 4 wk to air enriched with CO (30-100 ppm). Functional variables, reperfusion ventricular arrhythmias (VA) and cellular damages (infarct size, lactate dehydrogenase release) were assessed. Sarcomere length shortening and Ca(2+) handling were evaluated in intact isolated cardiomyocytes during a cellular anoxia-reoxygenation protocol. The major results show that prolonged CO exposure worsens myocardial I/R injuries, resulting in increased severity of postischemic VA, impaired recovery of myocardial function, and increased infarct size (60 +/- 5 vs. 33 +/- 2% of ischemic zone). The aggravating effects of CO exposure on I/R could be explained by a reduced myocardial enzymatic antioxidant status (superoxide dismutase -45%; glutathione peroxidase -49%) associated with impaired intracellular Ca(2+) handling. In conclusion, our results are consistent with the idea that chronic CO pollution dramatically increases the severity of myocardial I/R injuries.

Moderate exercise prevents impaired Ca2+ handling in heart of CO-exposed rat: implication for sensitivity to ischemia-reperfusion.

Sustained urban carbon monoxide (CO) exposure exacerbates heart vulnerability to ischemia-reperfusion via deleterious effects on the antioxidant status and Ca(2+) homeostasis of cardiomyocytes. The aim of this work was to evaluate whether moderate exercise training prevents these effects. Wistar rats were randomly assigned to a control group and to CO groups, living during 4 wk in simulated urban CO pollution (30-100 parts/million, 12 h/day) with (CO-Ex) or sedentary without exercise (CO-Sed). The exercise procedure began 4 wk before CO exposure and was maintained twice a week in standard filtered air during CO exposure. On one set of rats, myocardial ischemia (30 min) and reperfusion (120 min) were performed on isolated perfused rat hearts. On another set of rats, myocardial antioxidant status and Ca(2+) handling were evaluated following environmental exposure. As a result, exercise training prevented CO-induced myocardial phenotypical changes. Indeed, exercise induced myocardial antioxidant status recovery in CO-exposed rats, which is accompanied by a normalization of sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a expression and then of Ca(2+) handling. Importantly, in CO-exposed rats, the normalization of cardiomyocyte phenotype with moderate exercise was associated with a restored sensitivity of the myocardium to ischemia-reperfusion. Indeed, CO-Ex rats presented a lower infarct size and a significant decrease of reperfusion arrhythmias compared with their sedentary counterparts. To conclude, moderate exercise, by preventing CO-induced Ca(2+) handling and myocardial antioxidant status alterations, reduces heart vulnerability to ischemia-reperfusion.

Abnormal vascular reactivity at rest and exercise in obese boys.

BACKGROUND: Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild-to-moderate obesity and in lean controls. MATERIALS AND METHODS: Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23.9+/-2.6 kg m(-2))] and thirteen controls (BMI:17.4+/-1.8 kg m(-2)), matched for age (mean age: 11.6+/-0.6 years) were recruited. We measured carotid intima-media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow-mediated dilation (FMD) and nitrate-dependent dilation (NDD), lower limb blood flow during local knee-extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose. RESULTS: Compared to lean controls, obese boys had greater IMT (0.47+/-0.06 vs. 0.42+/-0.03 mm, P<0.05) but lower FMD (4.6+/-2.8 vs. 8.8+/-3.2%, P<0.01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min(-1).100 g(-1)) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity. CONCLUSIONS: Mild-to-moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity.

Two months of endurance training does not alter diastolic function evaluated by TDI in 9-11-year-old boys and girls.

OBJECTIVE: Superior global cardiac performance (ie stroke volume) is classically reported after training in children. Current knowledge of the impact of exercise training on myocardial relaxation, a major component of left ventricular (LV) filling and subsequently stroke volume, is, however, limited in the paediatric population. This study aimed to investigate the effect of aerobic training on LV wall motion velocities by tissue Doppler imaging (TDI) in healthy children. METHODS: 25 children (11 girls, 14 boys) were enrolled in a 2 month high-intensity aerobic training programme and 25 (12 girls and 13 boys) served as controls. The children (9-11 years old) performed a graded maximal exercise test on a treadmill to evaluate maximal oxygen uptake. Standard Doppler echocardiography and TDI measurements were performed at baseline and end of the study. Tissue Doppler systolic, early and late myocardial velocities were obtained at the mitral annulus in the septal, lateral, inferior and posterior walls. RESULTS: Maximal oxygen uptake increased by 6.5% (before: 51.6 (SD 4.2), after: 55.0 (4.5) ml/min/kg p<0.001) after training. A modest but significant increase in left ventricular end-diastolic diameter was also noticed (before: 46.1 (3.4), after: 48.3 (4.3) mm.BSA(-1/2), p<0.001), whereas left ventricular wall thickness and mass were unchanged. Neither transmitral inflow velocities nor early and late wall motion (Em: before = 18.4 (2.7), after = 18.0 (2.3) cm/s, Am: before = 6.8 (1.2), after = 6.7 (1.3) cm/s) were affected by training. Shortening fraction and regional systolic function (Sm: before = 10.1 (1.6), after = 10.2 (1.4) cm/s) by TDI were also unchanged. CONCLUSION: High-intensity aerobic sessions repeated over a 2 month period failed to improve regional diastolic function assessed by TDI in healthy young children.

Alteration in left ventricular normal and shear strains evaluated by 2D-strain echocardiography in the athlete's heart.

The contraction of cardiomyocytes induces a systolic increase in left ventricular (LV) normal (radial, circumferential and longitudinal) and shear strains, whose functional consequences have not been evaluated, so far, in athletes. We used 2D ultrasound speckle tracking imaging (STI) to evaluate LV regional strain in high-level cyclists compared to sedentary controls. Sixteen male elite cyclists and 23 sedentary controls underwent conventional, tissue Doppler, and STI echocardiography at rest. We assessed LV long and short axis normal strains and shear strains. We evaluated circumferential-longitudinal shear strain from LV torsion, and circumferential-radial shear strain from the difference between subendocardial and subepicardial torsion. Apical radial strain (42.7 +/- 10.5% versus 52.2 +/- 14.3%, P < 0.05) and LV torsion (6.0 +/- 1.8 deg versus 9.2 +/- 3.2 deg, P < 0.01) were lower in cyclists than in controls, respectively. Rotations and torsion were higher in the subendocardial than in the subepicardial region in sedentary controls, but not in cyclists. Haemodynamic and tissue Doppler based indexes of global LV diastolic and systolic functions were not different between cyclists and controls. Athlete's heart is associated with specific LV adaptation including lower apical strain and lower myocardial shear strains, with no change in global LV diastolic and systolic function. These mechanical alterations could improve the cardiovascular adjustments to exercise by increasing the radial strain and torsional (and thus untwisting) response to exercise, a key element of diastolic filling and thus of cardiac performance in athletes.

[Adipose epicardial tissue association with subclinical systolic dysfunction detected by longitudinal strain in diabetic patients with poor glycemic control]. / Association entre tissu adipeux epicardique et dysfonction systolique infraclinique détectée par strain longitudinal chez les diabétiques mal équilibrés.

OBJECTIVE: The aim of this study is to assess the association between epicardial adipose tissue (EAT) and infraclinical myocardial dysfunction detected by strain imaging in diabetic patients (T2DM) with poor glycemic control. METHODS: 22 patients with T2DM and 22 healthy control subjects of similar age and sex were prospectively recruited. Echocardiographic parameters were investigated. RESULTS: In comparison to controls, diabetic patients had significantly higher body mass index (27.7 vs. 24.6; P<0.01), waist perimeter (103 vs. 84; P<0.001) and usCRP level (5.4 vs. 1.5; P<0.01). On echocardiography; no differences were found in terms of ejection fraction or ventricular mass; however, patients with T2DM had significantly thicker EAT (8.7±0.7 vs. 3.0±1.0; P<0.001) and altered systolic longitudinal strain (-18.8±3.2 vs. 22.3±1.6; P<0.001). On multivariate analysis, EAT was identified as an independent contributor (ß=0,46, P=0.001) to systolic longitudinal strain. CONCLUSION: In patients with T2DM and poor glycemic control; EAT was associated with infraclinical systolic dysfunction evaluated by global longitudinal strain despite normal at rest ejection fraction and no coronary artery disease.

Aortic vasoconstriction related to smooth muscle cells ET-A and ET-B receptors is not involved in hypoxia-induced sustained systemic arterial hypertension in rats.

OBJECTIVES: We report in the present study the role of endothelin (ET-1) and ET-1 receptors in the sustained hypoxia-induced systemic hypertension. METHODS: Wistar rats were randomly assigned to live continuously in hypobaric hypoxia (CH rats) or normoxia (N rats). At the end of hypoxic stress exposure (5 weeks at 450 mm Hg), measurements of mean systemic arterial pressure were done. The effects of ET-1 in the presence or not of the endothelium and/or of specific ET-A inhibitors (BQ-123) or ET-B inhibitors (BQ-788), have been investigated in an isolated model of rat thoracic aorta. Finally, plasmatic ET-1 concentrations have been determined by assay procedure. RESULTS: Following five weeks of chronic hypoxic stress, CH rats presented a significant increase of mean systemic arterial pressure (N: 129.1+/-6.8 mm Hg vs CH: 152.5+/-3.4 mm Hg; P<0.05). Despite of this hypoxia-induced hypertension, ET-1 plasmatic concentration was not different between N and CH rats. Finally, CH rats presented a reduce response to ET-1 when compared to N rats. This phenomenon seems to be associated to the ET-A vascular smooth muscle cell receptors, since difference between N and CH rats was still present in endothelium denuded aortic rings in the presence or not of the specific ET-B inhibitors (BQ-788). In addition, in the presence of the specific ET-A inhibitor (BQ-123) response to ET-1 was abolished in N and CH rats to the same extent (N:-98%; CH:-99%). CONCLUSION: This work clearly suggests that, following long term exposure to hypoxia, ET-1 and ET-1 receptors are not involved in the persistence of systemic hypertension in a rat model, and that chronic exposure to severe hypoxic stress was associated with a downregulation of the ET-A receptors response to ET-1.

Effects of high-altitude exercise training on contractile function of rat skinned cardiomyocyte.

OBJECTIVE: Previous studies have questioned whether there is an improved cardiac function after high-altitude training. Accordingly, the present study was designed specifically to test whether this apparent blunted response of the whole heart to training can be accounted for by altered mechanical properties at the cellular level. METHODS: Adult rats were trained for 5 weeks under normoxic (N, NT for sedentary and trained animals, respectively) or hypobaric hypoxic (H, HT) conditions. Cardiac morphology and function were evaluated by echocardiography. Calcium Ca2+ sensitivity of the contractile machinery was estimated in skinned cardiomyocytes isolated from the left ventricular (LV) sub-epicardium (Epi) and sub-endocardium (Endo) at short and long sarcomere lengths (SL). RESULTS: Cardiac remodelling was harmonious (increase in wall thickness with chamber dilatation) in NT rats and disharmonious (hypertrophy without chamber dilatation) in HT rats. Contrary to NT rats, HT rats did not exhibit enhancement in global cardiac performance evaluated by echocardiography. Stretch- dependent Ca2+ sensitization of the myofilaments (cellular index of the Frank-Starling mechanism) increased from Epi to Endo in N rats. Training in normoxic conditions further increased this stretch-dependent Ca2+ sensitization. Chronic hypoxia did not significantly affect myofibrilar Ca2+ sensitivity. In contrast, high-altitude training decreased Ca2+ sensitivity of the myofilaments at both SL, mostly in Endo cells, resulting in a loss of the transmural gradient of the stretch-dependent Ca2+ sensitization. Expression of myosin heavy chain isoforms was affected both by training and chronic hypoxia but did not correlate with mechanical data. CONCLUSIONS: Training at sea level increased the transmural gradient of stretch-dependent Ca2+ sensitization of the myofilaments, accounting for an improved Frank-Starling mechanism. High-altitude training depressed myofilament response to Ca2+, especially in the Endo layer. This led to a reduction in this transmural gradient that may contribute to the lack of improvement in LV function via the Frank-Starling mechanism.

Left ventricles of aging athletes: better untwisters but not more relaxed during exercise.

OBJECTIVE: With an aging population and the increasing prevalence of heart failure with preserved ejection fraction, developing strategies to prevent diastolic dysfunction is crucial. Regular endurance training has been suggested to be one such strategy. However, the underlying mechanisms of training, including the effect on left ventricular (LV) untwist, which promotes LV filling, are unclear and studies exploring the heart during exercise in the aging heart are lacking. METHODS: Cardiopulmonary exercise testing with speckle tracking echocardiography was realized in male subjects: 16 young athletes (YA), 19 young controls (YC), 22 middle-aged athletes (MA) with a lifelong history of endurance training, and 20 middle-aged controls (MC). RESULTS: During exercise, the early filling was lower in MC compared to YC, whereas it was preserved between YA and MA. At exercise, peak untwisting rate/peak twist ratio and the percentage of untwist during isovolumic relaxation time were decreased in senior groups but higher in YA and MA compared to age-matched controls. Early diastolic filling reserve correlated with untwisting rate/peak twist reserve in YA and MA (R 2 = 0.22, p < 0.05) but not in controls. LV relaxation indices in athletes at rest and during exercise were not improved compared to age-matched controls. CONCLUSION: LV intrinsic relaxation was similarly lower with age, independently of training, while the age-related decrease of untwist during exercise was lower with lifelong exercise training. The preservation of untwist mechanics in MA could thus sustain the early filling during exercise. Further studies are needed to confirm the role of exercise training as a preventive strategy for diastolic dysfunction and heart failure.

Chronic exercise does not prevent hypoxia-induced increased aortic sensitivity to endothelin in rats.

OBJECTIVES: We report in the present study the effect of regular exercise on vascular reactivity alterations to endothelin (ET-1) following prolonged exposure to hypoxic stress. METHODS: Male Dark Agouti rats were randomly assigned to N (sedentary rats), NCE (normoxic exercised rats), CH (chronic hypoxic sedentary rats) and CHCE (chronic hypoxic exercised rats) groups. The effects of ET-1 in the presence or not of the endothelium and/or of the specific inhibitor, bosentan, have been investigated in an isolated model of rat thoracic aorta. RESULTS: Prolonged exposure to hypoxia induced a significant increase in aortic sensitivity to ET-1 (-log ED50 in CH = 8.15 +/- 0.01 vs in N = 7.98 +/- 0.02, p < 0.05). Despite exercise training reduced the sensitivity to ET-1 in normoxic rats, it has no effects in hypoxic rats (-log ED50 in CH = 8.15 +/- 0.01 vs in CHCE = 8.19 +/- 0.01, NS). Moreover, although the removal of endothelium has no effect in N rats, it leads, in NCE rats, to a significant increase in sensitivity to ET-1 (-log ED50 in endothelium intact rings = 7.89 +/- 0.04 vs in denuded rings = 8.04 +/- 0.02, p < 0.05). The implication of ET-1 receptors on both endothelial and smooth muscle cells is confirmed by the significant reduced sensitivity to ET-1 in the four groups when bosentan is present in organ bath. CONCLUSION: Our study clearly suggests that part of the beneficial effect of chronic exercise could be mediated by enhancing endothelial function associated with endothelin reactivity in peripheric vessels. However, chronic exercise training does not seem to be able to limit the increased vasoconstriction to ET-1 stimulation induced by chronic hypoxia exposure.

Reproducibility of automated pulse wave velocity measurement during exercise. Running head: pulse wave velocity during exercise.

Pulse wave velocity measurement is used as an index of arterial stiffness. The purpose was to evaluate the reproducibility of pulse wave velocity measurement at rest, during exercise and recovery from exercise, using an automated device. Twelve healthy young adults (mean age 22.0 +/- 3.1 yrs) underwent an upright submaximal cycle test on two separate occasions, one week apart. Pulse wave velocity, systolic and diastolic blood pressures and heart rate were assessed at rest, during the last 2 min of exercise and 10 min later. Pulse wave velocity was measured on the upper limb and the forearm by the cross-correlation function of photoplethysmography and Doppler signals. Brachial artery pulse wave velocity was calculated from upper limb and forearm pulse wave velocities. No significant difference was found on duplicate measurements of heart rate, systolic and diastolic blood pressures at rest, during exercise and recovery, showing that pulse wave velocity was measured under similar conditions. Coefficient of variation for upper limb and forearm pulse wave velocities ranged from 2.9 to 5.9% at rest and during recovery, and were respectively 2.9% and 8.3% during exercise. However, coefficient of variation for brachial pulse wave velocity was 7.7 and 10.3% at rest, 15.7% during exercise, and 5.8% during recovery. During exercise, pulse wave velocity measurements were satisfying, but indirect assessment of brachial artery pulse wave velocity showed poor reproducibility. Thus, upper limb and forearm pulse wave velocities may be used during exercise to assess the effect of training or drugs on arterial wall mechanical properties.

Cardiac remodeling and functional adaptations consecutive to altitude training in rats: implications for sea level aerobic performance.

This study questioned the effect of living and training at moderate altitude on cardiac morphological and functional adaptations and tested the incidences of potential specific adaptations compared with aerobic sea level training on maximal left ventricular performance. Sea level-native rats were randomly assigned to N (living in normoxia), NT (living and training 5 days/wk for 5 wk in normoxia), CH (living in hypoxia, 2,800 m), and CHT (living and training 5 days/wk for 5 wk in hypoxia, 2,800 m) groups. Cardiac adaptations were evaluated throughout the study period by Doppler echocardiography. Maximal stroke volume (LV(SVmax)) was measured during volume overloading before and after the study period. Finally, at the end of the study period, passive pressure-volume relationships on isolated heart and cardiac weighing were obtained. Altitude training resulted in a specific left ventricular (LV) remodeling compared with NT, characterized by an increase in wall thicknesses without any alteration in internal dimensions. These morphological adaptations associated with hypoxia-induced alterations in pulmonary outflow and preload conditions led to a decrease in LV filling and subsequently no improvement in LV performance during resting physiological conditions in CHT compared with NT. Such a lack of improvement was confirmed during volume overloading that simulated maximal effort (LV(SVmax) pretest: NT = 0.58 +/- 0.05, CHT = 0.57 +/- 0.08 ml; posttest: NT = 0.72 +/- 0.06, CHT = 0.58 +/- 0.07 ml; NT vs. CHT in posttest session, P < 0.05). Maximal aerobic velocities increased to the same extent in NT and CHT rats despite marked polycythemia in the latter. The lack of LV(SVmax) improvement resulting from altitude training-induced cardiac morphological and functional adaptations could be responsible for this phenomenon.

Chronic hypoxia exposure depresses aortic endothelium-dependent vasorelaxation in both sedentary and trained rats: involvement of L-arginine.

This study was designed to test the hypothesis that the previously demonstrated training-induced improvement of the endothelium vasodilator function would be blunted under conditions of chronic hypoxia exposure as a result of deleterious effects of hypoxia per se on the nitric oxide pathway. Sea-level-native rats were randomly assigned to N (living in normoxia), NT (living and training 5 days/wk for 5 wk in normoxia), CH (living in hypoxia, 2,800 m), and CHT (living and training 5 days/wk for 5 wk in hypoxia, 2,800 m) groups. Concentration-response curves to acetylcholine (ACh; 10(-9) to 10(-4) M) with or without L-arginine (10(-3) to 10(-5) M) and/or nitro-L-arginine methyl ester (10(-5) M) were assessed on aortic isolated rings. The main finding was that chronic hypoxia severely depressed maximal ACh-responses of aortic rings in both sedentary and trained groups. However, chronic hypoxia did not interfere with training-induced increases in maximal ACh responses, considering that maximal ACh vasorelaxation was improved in CHT rats to the same extent as in NT rats when both groups were directly compared with their sedentary counterparts. It should be pointed out that the vasodilator response to ACh was restored in CH and CHT rats to the level obtained in N and NT rats, respectively, by an in vitro L-arginine addition. A hypoxia-induced decrease in L-arginine bioavailability resulting from acclimatization at altitude may be involved in this limitation of the NO pathway in CH and CHT rats. These results are of importance for aerobic performance as the specific vascular adaptations to training at altitude could contribute to limit peripheral vasodilatation and subsequently blood flow during exercise.

Cardiorespiratory dynamics to hypoxia at the onset of cycling exercise in male endurance subjects.

AIM: It is well established that altering O2 delivering to contracting skeletal muscle affects human performance. In this respect, a reduced O2 supply (e.g., hypoxia) increases the rate of muscle fatigue. This study aimed to determine the effects of moderate hypoxia and exercise intensity on oxygen uptake (VO2) and cardiac output (CO) kinetics during moderate [below the ventilatory threshold (VT)] and heavy (above VT) constant work rate cycling exercises. METHODS: Eight trained males (age, mean+/-SD, 22+/-3 years; height 182+/-5 cm; body mass 71+/-12 kg) performed at the same relative intensity in normoxic (FIO2=0.21) and hypoxic (FIO2=0.13) conditions moderate and heavy exercises during which pulmonary gas exchange was determined breath-by-breath and CO was monitored beat-by-beat with Doppler echocardiography. RESULTS: The rate of increase (t63%, corresponding to time constant and time delay of a monoexponential response) in CO was significantly faster than that of VO2 in 3 out of 4 experimental conditions (p<0.05). Moreover VO2 kinetics were significantly slowed by hypoxia and speeded by exercise intensity, while CO responses were unaffected by such conditions. A slowed CO response was apparent in hypoxia compared to normoxia (p>0.05) in heavy exercise. CONCLUSIONS: These results suggest an absence of coupling between CO and VO2 kinetics, and that cardiorespiratory O2 delivery is likely different at exercise onset as a function of exercise intensity and FIO2.

Effect of chronic hypoxia and socioeconomic status on VO2max and anaerobic power of Bolivian boys.

The aim of this work was to analyze the effects of altitude and socioeconomic and nutritional status on maximal oxygen uptake (VO2max) and anaerobic power (P) in 11-yr-old Bolivian boys. At both high (HA) (3,600 m) and low (LA) (420 m) altitudes, the boys were divided into high (HA1, n = 23, LA1, n = 48) and low (HA2, n = 44, LA2, n = 30) socioeconomic levels. Anthropometric characteristics, VO2max, and P [maximal P (Pmax) during a force-velocity test and mean P (P) during a 30-s Wingate test] were measured. Results showed that 1) anthropometric parameters were not different between HA1 and LA1 and HA2 and LA2 boys, but HA2 and LA2 boys were two years behind HA1 and LA1 boys in development; 2) VO2max was not different in boys from the same altitude, but at HA VO2max was 10% lower than at LA (HA1 = 37.2 +/- 5.6, HA2 = 38.9 +/- 6.4, LA1 = 42.5 +/- 5.8, LA2 = 42.5 +/- 5.3 ml.min-1 x kg-1 body wt); and 3) Pmax and P were higher in well-nourished than in undernourished boys, but there was no difference in Pmax and P between HA1 and LA1 and HA2 and LA2 boys (HA1 = 6.8 +/- 1.0, HA2 = 5.5 +/- 0.8, LA1 = 7.1 +/- 1.0, LA2 = 5.3 +/- 0.9 W/kg for Pmax; HA1 = 5.2 +/- 0.8, HA2 = 4.5 +/- 0.9, LA1 = 5.2 +/- 0.7, LA2 = 4.0 +/- 0.6 W/kg for P).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of altitude and socioeconomic status on VO2max and anaerobic power in prepubertal Bolivian girls.

The aim of this work was to evaluate the effects of high altitude and low socioeconomic status (SES) on aerobic and anaerobic power in 11-yr-old Bolivian girls. At both high (3,600 m) and low (420 m) altitudes, low-SES groups of girls were compared to similarly aged, high-SES girls. At low altitude, low-SES girls were also compared with younger high-SES girls with the same anthropometric characteristics. Anthropometric data were similar between high-SES and low-SES girls at both altitudes, but low-SES girls showed a 9-mo growth delay. Maximal O2 uptake was significantly lower for low-SES girls at both altitudes. Values did not differ when expressed relative to body weight at high altitude for high-SES vs. low-SES girls (37.6 +/- 1.2 vs. 39.3 +/- 1.0 ml.min-1.kg body wt-1), but a difference persisted at low altitude between high- and low-SES girls (37.5 +/- 1.0 vs. 34.7 +/- 0.7 ml.min-1.kg body wt-1). Anaerobic power (Pmax, force-velocity test; Pwing, Wingate test) was reduced for low-SES girls at both altitudes, whatever the mode of expression. For a given SES, the relative anaerobic performances were lower at low altitude. At low altitude, low-SES girls developed lower anaerobic power than did younger high-SES girls with similar anthropometric characteristics. In conclusion, at both altitudes, the reduction of anaerobic performances observed in girls of low SES could not be totally explained by anthropometric factors. Structural and/or functional muscle alterations are suggested. Moreover, at low altitude, tropical and other factors may have contributed to differences in performance between low- and high-SES girls.

[Study of the reproducibility of cardiac output measurement during exercise in pre-pubertal children by doppler echocardiography and CO2 inhalation]. / Etude de la reproductibilité de la mesure du débit cardiaque à l'exercice chez l'enfant prépubère par échocardiographie doppler et par réinhalation de CO2.

Non-invasive measurement of the cardiac output is essential in investigations of healthy children. However, the data concerning the reproducibility of the measurements are very limited. The aim of this study was to assess the reproducibility of the measurement of cardiac output during exercise by Doppler echocardiography and reinhalation of CO2 (extrapolation method). Fourteen pre-pubertal children underwent two similar tests at increasingly intense levels of exercise. The cardiac output was measured at rest and during the last minute of each stepwise increment of exercise. The results show no difference between the cardiac outputs of the two tests, whichever method was used and at all levels of exercise. They also demonstrate a better reproducibility of cardiac output measurement by Doppler echocardiography (coefficient of variation: 7.5% at rest and 5.2% at maximal effort) compared with reinhalation of CO2 (coefficient of variation: 16.8% at rest and 11.7% at maximal effort). Both methods showed better reproducibility on exercise, resulting from smaller variations in heart rate and stroke volume on effort than at rest. The authors conclude that Doppler echocardiography is very accurate and its simplicity makes it the method of choice in pre-pubertal children for measuring cardiac output during exercise.

Parotid gland swelling.

The salivary glands are seldom noticed by the physician when they are functioning properly, but they cause vexing problems in diagnosis and management during times of their disordered function. One reason for this is that numerous salivary diseases have similar onsets and patterns of symptomatology. Another reason is that the clinical expression of these diseases is often similar, including pain, diffuse swelling, and altered salivary discharge. This paper enumerates useful points of differentiation which may be elicited from the history and physical examination to distinguish among parotid diseases. If management is to be successful, it must be based on (1) identification of the etiology of the pathologic process, and (2) the institution of therapeutic measures designed to eliminate the etiology of the disease, and restore, as closely as possible, the normal physiology of the gland.