High-intensity intermittent training is as effective as moderate continuous training, and not deleterious, in cardiomyocyte remodeling of hypertensive rats.

Exercise training offers possible nonpharmacological therapy for cardiovascular diseases including hypertension. High-intensity intermittent exercise (HIIE) training has been shown to have as much or even more beneficial cardiovascular effect in patients with cardiovascular diseases than moderate-intensity continuous exercise (CMIE) training. The aim of this study was to investigate the effects of the two types of training on cardiac remodeling of spontaneously hypertensive rats (SHR) induced by hypertension. Eight-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were divided into four groups: normotensive and hypertensive control (WKY and SHR-C) and hypertensive trained with CMIE (SHR-T CMIE) or HIIE (SHR-T HIIE). After 8 wk of training or inactivity, maximal running speed (MRS), arterial pressure, and heart weight were all assessed. CMIE or HIIE protocols not only increased final MRS and left ventricular weight/body weight ratio but also reduced mean arterial pressure compared with sedentary group. Then, left ventricular tissue was enzymatically dissociated, and isolated cardiomyocytes were used to highlight the changes induced by physical activity at morphological, mechanical, and molecular levels. Both types of training induced restoration of transverse tubule regularity, decrease in spark site density, and reduction in half-relaxation time of calcium transients. HIIE training, in particular, decreased spark amplitude and width, and increased cardiomyocyte contractility and the expression of sarco(endo)plasmic reticulum Ca2+-ATPase and phospholamban phosphorylated on serine 16. NEW & NOTEWORTHY High-intensity intermittent exercise training induces beneficial remodeling of the left ventricular cardiomyocytes of spontaneously hypertensive rats at the morphological, mechanical, and molecular levels. Results also confirm, at the cellular level, that this type of training, as it appears not to be deleterious, could be applied in rehabilitation of hypertensive patients.

Structural, Contractile and Electrophysiological Adaptations of Cardiomyocytes to Chronic Exercise.

Cardiac beneficial effects of chronic exercise is well admitted. These effects mainly studied at the organ and organism integrated levels find their origin in cardiomyocyte adaptation. This chapter try to highlight the main trends of the data related to the different parameters subject to such adaptations. This is addressed through cardiomyocytes size and structure, calcium and contractile properties, and finally electrophysiological alterations induced by training as they transpire from the literature. Despite the clarifications needed to decipher healthy cardiomyocyte remodeling, this overview clearly show that cardiac cell plasticity ensure the cardiac adaptation to exercise training and offers an interesting mean of action to counteract physiological disturbances induced by cardiac pathologies.

Ventilatory response to exercise does not evidence electroencephalographical respiratory-related activation of the cortical premotor circuitry in healthy humans.

AIM: The neural structures responsible for the coupling between ventilatory control and pulmonary gas exchange during exercise have not been fully identified. Suprapontine mechanisms have been hypothesized but not formally evidenced. Because the involvement of a premotor circuitry in the compensation of inspiratory mechanical loads has recently been described, we looked for its implication in exercise-induced hyperpnea. METHODS: Electroencephalographical recordings were performed to identify inspiratory premotor potentials (iPPM) in eight physically fit normal men during cycling at 40 and 70% of their maximal oxygen consumption ((V)·O(2max) ). Relaxed pedalling (0 W) and voluntary sniff manoeuvres were used as negative and positive controls respectively. RESULTS: Voluntary sniffs were consistently associated with iPPMs. This was also the case with voluntarily augmented breathing at rest (in three subjects tested). During the exercise protocol, no respiratory-related activity was observed whilst performing bouts of relaxed pedalling. Exercise-induced hyperpnea was also not associated with iPPMs, except in one subject. CONCLUSION: We conclude that if there are cortical mechanisms involved in the ventilatory adaptation to exercise in physically fit humans, they are distinct from the premotor mechanisms activated by inspiratory load compensation.

(1)H NMR-based metabolomics approach for exploring urinary metabolome modifications after acute and chronic physical exercise.

Metabolomics is a comprehensive method for metabolite assessment that involves measuring the overall metabolic signature of biological samples. We used this approach to investigate biochemical changes due to acute and chronic physical exercise. Twenty-two women using identical oral contraceptives were segregated into an untrained (n = 10) or trained (n = 12) group depending on their physical training background. The subjects performed two exercises in a randomized order: a prolonged exercise test (75% of their VO(2 max) until exhaustion) and a short-term, intensive exercise test (short-term, intensive exercise anaerobic test). Urine specimens were collected before and 30 min after each test. The samples were analyzed by (1)H NMR spectroscopy, and multivariate statistical techniques were utilized to process the data. Distinguishing characteristics were observed only in the urine profiles of specimens collected before vs. 30 min after the short-term, intensive exercise test. The metabolites responsible for such changes were creatinine, lactate, pyruvate, alanine, beta-hydroxybutyrate, acetate, and hypoxanthine. In both groups, the excretion of lactate, pyruvate, alanine, beta-hydroxybutyrate, and hypoxanthine increased similarly after the completion of the short-term, intensive exercise test (p < 0.03). However, acetate excretion increased to a lesser extent in trained than in untrained subjects (p < 0.05). In conclusion, metabolomics is a promising tool in order to gain insight into physiological status and to clarify the changes induced by short-term, intense physical exercise.

Putative protective effect of inspiratory threshold loading against exercise-induced supraspinal diaphragm fatigue.

The present investigation was intended to assess the consequences of an inspiratory load on the diaphragm central component of fatigue during exercise. We recorded the motor potential evoked (MEP) by transcranial magnetic stimulation of the motor cortex in 10 subjects. The diaphragm and rectus femoris were studied before and 10, 20, and 40 min after two 16-min cycling exercise (E) trials requiring 55% of maximal oxygen uptake: 1) one with an inspiratory threshold load (E + ITL), corresponding to 10% of maximal inspiratory pressure; and 2) the other without the load (E). Dyspnea, heart rate, electromyographic activity of the sternocleidomastoid, and diaphragm work were significantly higher in E + ITL than in E. Neither trial affected the response to phrenic magnetic stimulation, which was performed 15 and 25 min postexercise, or the maximal inspiratory pressure (116 and 120 cm H(2)O before E and E + ITL, respectively, and 110 and 114 cm H(2)O at 30 min postexercise). Whereas the amplitude of the diaphragm MEP was unaffected by E + ITL (+2.1 +/- 29.4%), a significant decrease was observed 10 min after E compared with baseline (-37.1 +/- 22.3%) and compared with E + ITL. The MEP amplitude of rectus femoris remained unchanged with E and E + ITL. The recruitment of synergistic agonists during E + ITL may have normalized the major ventilatory stress and reset up the excitability of the diaphragm pathway.

Mouth pressure twitches induced by cervical magnetic stimulation to assess inspiratory muscle fatigue.

This study aimed at determining whether twitch mouth pressure (TwPmo) induced by cervical magnetic stimulation (CMS) was sensitive to inspiratory muscle fatigue produced by whole body exercise (WBE) in normal subjects. Twenty subjects performed one or two of the following protocols: (i). cycling at 85% V(O(2),max) until exhaustion; (ii). inspiratory resistive load (IRL) breathing at 62% of maximal inspiratory pressure until task failure. In eight subjects, oesophageal (TwPoes), gastric (TwPga) and transdiaphragmatic (TwPdi) pressures were recorded. The TwPmo was significantly reduced (P<0.05) 20 min after both WBE and IRL, from 17.5+/-4.4 to 15.9+/-3.9 cmH(2)O and from 19.4+/-4.9 to 17.7+/-4.5 cmH(2)O, respectively. Subsequently to IRL, the TwPdi decrease was associated with a reduction in TwPoes/TwPga ratio; not after WBE. Independently of the mode of ventilatory loading, inspiratory muscle fatigue was detected. Thus, inspiratory muscle fatigue after WBE can be assessed in normal subjects with a noninvasive technique.

Contribution of respiratory acidosis to diaphragmatic fatigue at exercise.

The factors that may modulate ventilatory muscle fatigue during exercise are controversial. In this study the contribution of acidosis to exercise-induced diaphragmatic fatigue was investigated, using measurements of the twitch mouth pressure response (tw,Pmo) to cervical magnetic stimulation. After learning sessions, 14 healthy subjects performed two cycling tests (at 60% of maximal aerobic power for 16 min), one while breathing spontaneously (mean minute ventilation (V'E) 67.9 L x min(-1)) and the other while hypoventilating voluntarily (mean V'E 53.8 L x min(-1)). Exercise was voluntarily set at a moderate power to avoid a fatiguing effect of exercise per se. As compared with spontaneous breathing (SB), voluntary hypoventilation (VHV) significantly increased mean carbon dioxide tension in arterial blood (Pa,CO2) (51 mmHg versus 41 mmHg) and significantly decreased arterial pH (7.28 versus 7.34). After 10 min of SB test, tw,Pmo was unchanged compared to the baseline value (19.1 versus 18.5 cmH2O) whereas tw,Pmo fell significantly as compared to baseline (17.1 versus 18.5 cmH2O) and to SB (17.1 versus 19.1 cmH2O) after the VHV test. The results of this study suggest that exposure to hypercapnia may impair respiratory muscle function. This impairment could be more clinically relevant in patients with chronic obstructive lung disease.

Optimization characteristics of walking with and without a load on the trunk of the body.

Previous work showed that subjects naturally adopt a walking speed which optimizes energy cost of locomotion and stability of stride; however, no studies have examined whether these criteria are affected by carrying an external load. The purpose of this study was to compare optimization characteristics during loaded or unloaded walking. Energy cost and stride characteristics were measured for 10 subjects with and without a load on the trunk of the body of 10% of the body weight during 4 sessions. The first 2 sessions represent free walking at 2.5, 3, 3.5, 4, 4.5, and 5 km x hr.(-1). The last sessions represent free vs forced walking at constant speed (preferred frequency and +/- 10 PF and +/-20% of preferred frequency). Results show an effect of load on energy cost of walking but no effect on the optimal speed for stability. Furthermore, when carrying a load the subject does not adopt systematically the speed that minimizes physiological cost. Our findings suggest the necessity to consider this effect to prevent gait disturbance and maintain the health benefits of walking.

Endothelin-1 inhibits L-type Ca2+ current enhanced by isoprenaline in rat atrial myocytes.

Endothelin-1 (ET-1) was shown to exert direct cardiac effects by complex signaling pathways and to interact with neurotransmitter regulation of cardiac activity. The effect of ET-1 was investigated on the beta-adrenergic stimulation of cardiac L-type Ca2+ current (ICaL) on isolated rat atrial myocytes by using the patch-clamp technique. ET-1 (5 x 10(-8) M) reversed the increase in ICaL induced by isoprenaline (10(-6) M) but had no effect on basal ICaL and on (-) Bay K 8644-increased ICaL (10(-6) M); so ET-1 might exert an effect only when the Ca2+ channels are phosphorylated. The antiadrenergic action of ET-1, blocked by BQ-123 (10(-6) M) and unaffected by IRL 1038 (3.5 x 10(-8) M) should be mediated by ET-A receptors. The inhibitory action of ET-1 was still observed when ICaL was previously increased by forskolin (3 x 10(-6) M), 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP; 200 microM), or cAMP (100 microM) in presence of isobutyl methyl xanthine (IBMX; 10(-6) M), suggesting that the antiadrenergic action of ET-1 on ICaL was exerted independent of the cAMP-dependent phosphorylation pathway. ET-1 is known to be an activator of phosphoinositide hydrolysis, resulting in an increased production of IP3 and diacylglycerol (DAG). A Ca(2+)-dependent inhibition of ICaL consequently to an elevation of the intracellular Ca2+ pool via IP3 might be excluded in the action of ET-1, because of the presence of EGTA in the intrapipette medium. ET-1 reversed the isoprenaline-induced increase in ICaL in the presence of protein kinase C inhibitor [PKC(19-31); 100 microM), making unlikely the involvement of a DAG-dependent activation of PKC. Therefore the antiadrenergic action of ET-1 might also be independent on the phosphoinositide pathway.

Antagonism of beta-adrenergic stimulation of L-type Ca2+ current by endothelin in guinea-pig atrial cells.

Experiments carried out with isolated guinea pig atrial cells, using the patch clamp technique, demonstrated that endothelin-1 reversed the increase in L-type Ca2+ current (ICaL) induced by isoprenaline. Similar effects of endothelin-1 were observed when ICaL was previously increased by forskolin or 8-bromo-cAMP. These results suggested that the endothelin antagonism of beta-adrenergic stimulation of ICaL was exerted independently of the cAMP-dependent phosphorylation pathway.

[Voluntary poisoning by Cortinarius orellanus: usefulness of an original early treatment after determination of orellanine in the biological fluids and tissues]. / Intoxication volontaire par Cortinarius orellanus: intérêt d'un traitement précoce original après dosage de l'orellanine dans les milieux biologiques et tissulaires.

Cortinarius poisoning is generally caused by orellanine, a hydroxy bipyridine N, N-dioxide. This intoxication is characterized by acute nephritis which can lead to death without treatment. We reported a highly sensitive and simple fluorimetric technique to analyse orellanine by thin-layer chromatography on the basis of its characteristic photodecomposition into orelline. Using this procedure, we detected and assayed orellanine for the first time in plasma and renal biopsies of a woman who had deliberately ingested two fruit-bodies of Cortinarius orellanus. An early original treatment was carried out based on hemodialysis, combination plasmapheresis-hemoperfusion, and amino acids and diltiazem administration. These results indicate that it is now possible to make a precise diagnosis of orellanine poisoning.

[Comparative study of the antibacterial activity of cefpodoxime against enterobacteria producing beta lactamases]. / Etude comparative de l'activité antibactérienne du cefpodoxime sur les entérobactéries productrices de bêta lactamases.

Cefpodoxime proxetil (RU 51 807) is the oral prodrug of cefpodoxime (RU 51 763), a third generation cephalosporin. The antibacterial activity of cefpodoxime was compared with the activities of amoxicillin in combination with clavulanic acid (AUG), cefaclor (CCl), cefuroxime (CXM) and cefotaxime (CTX), against species of Enterobacteriaceae showing a resistance pattern against ampicillin (AMP), ticarcillin (TIC), cefalothin (CFT) and cefotaxime (CTX) respectively. For strains AMP and TIC R, CFT and CTX S, MICs 90% of cefpodoxime were 1 mg/l (E. coli), 0.5 (K. pneumoniae), 0.06 (P. mirabilis), 0.5 (Shigella sp.) and 1 (Salmonella sp.); they were 4 to 16 times as high for AUG -CCL -CXM and 4 to 16 times as low for CTX. For K. pneumoniae AMP and TIC R, CFT I/R and CTX S, similar résults were obsereved for the 5 beta-lactam antibiotics, but with an activity 10 times as low. Among the species AMP R, TIC S, CFT R and CTX S, cefpodoxime was active against P. rettgeri, P. stuartii, C. diversus, E. aerogenes and Y. enterocolitica (MICs 90% ranging from 2 to 4 mg/l; from 0.12 to 1 mg/l for CTX) and less active or inactive against P. vulgaris, E. cloacae, S. marcescens, M. morganii and E. coli (MICs 90% ranged from 16 to 32 mg/l; from 1 to 4 mg/l for CTX).(ABSTRACT TRUNCATED AT 250 WORDS)

[Outcome of acute renal failure caused by voluntary ingestion of Cortinarius orellanus]. / Evolution d'une insuffisance rénale aiguë par ingestion volontaire de Cortinarius orellanus.

Orellanin poisoning is characterized by an acute renal failure which can be lethal if the appropriate treatment is not given. A 31-year old woman was admitted to hospital 10 days after she had deliberately ingested 2 raw carpophores of the mushroom Cortinarius orellanus. Acute renal failure (creatininaemia 1,100 mumol/l) developed, requiring 6 sessions of haemodialysis, one of plasmapheresis and the administration of diltiazem and aminoacids. Plasma and tissue assays of orellanin, the mushroom's toxin, were performed by two-dimensional thin layer chromatography. Before haemodialysis and 10 days after ingestion of the poison, the plasma contained orellanin. Eighteen months after the attempted suicide, the plasma creatinine level was 181 mumol/l.

Intoxication by Cortinarius orellanus: detection and assay of orellanine in biological fluids and renal biopsies.

A woman suffering from acute tubulo-interstitial nephritis was admitted to the hospital ten days after deliberate intoxication by ingestion of Cortinarius orellanus. Orellanine, the main toxin responsible for orellanine poisoning, was detected in biological fluids and renal biopsies. It was assayed by direct spectrofluorimetry on two-dimensional thin-layer chromatograms after specific photodecomposition into orelline. The orellanine concentration was 6.12 mg/l in the plasma (10 days after ingestion). Orellanine levels in renal biopsies were 7 micrograms per 25 mm3 of the first biopsy (13 days after ingestion) and 24 micrograms per 8 mm3 of the second biopsy (6 months later).