Responses of skeletal muscle hypertrophy in Wistar rats to different resistance exercise models.

This study aimed to compare the effects of three different resistance exercise models on the quadriceps muscle cross-sectional area, as well as on mTOR phosphorylation and other pivotal molecules involved in the upstream regulation of mTOR. Twenty-four male Wistar rats were divided into untrained (control), endurance resistance training, strength resistance training, and hypertrophy resistance training (HRT) groups (n=6). After 12 weeks of training, the red portion of the quadriceps was removed for histological and Western blot analyses. The results showed that the quadriceps weight and cross-sectional areas in the exercised groups were higher than those of the untrained rats. However, the HRT group presented better results than the other two experimental groups. This same pattern was observed for mTOR phosphorylation and for the most pivotal molecules involved in the upstream control of mTOR (increase of PKB, 14-3-3, ERK, p38 MAPK, and 4E-BP1 phosphorylation, and reduction of tuberin, sestrin 2, REDD1, and phospho AMPK). In summary, our study showed that HRT leads to high levels of mTOR phosphorylation as well as of other proteins involved in the upstream regulation of mTOR.

Effects of physical exercise on the P38MAPK/REDD1/14-3-3 pathways in the myocardium of diet-induced obesity rats.

Obesity is associated with myocardial insulin resistance and impairment of the mammalian target of rapamycin (mTOR) signaling pathway. The activation of the mTOR cascade by exercise has been largely shown in skeletal muscle, but insufficiently analyzed in myocardial tissue. In addition, little is known regarding the mTOR upstream molecules in the hearts of obese animals and even less about the role of exercise in this process. Thus, the present study was aimed to evaluate the effects of physical exercise on P38 Mitogen-Activated Protein Kinase (P38MAPK) phosphorylation and the REDD1 (regulated in development and DNA damage responses 1) and 14-3-3 protein levels in the myocardium of diet-induced obesity (DIO) rats. After achievement of DIO and insulin resistance, Wistar rats were divided in 2 groups: sedentary obese rats and obese rats performed treadmill running (50-min/day, 5 days per week velocity of 1.0 km/h for 2 months). Forty-eight hours after the final physical exercise, the rats were killed, and the myocardial tissue was removed for Western blot analysis. DIO increased the REDD1 protein levels and reduced the 14-3-3 protein levels and P38MAPK, mTOR, P70S6k (p70 ribosomal S6 protein kinase), and 4EBP1 (4E-binding protein-1) phosphorylation. Interestingly, physical exercise reduced the REDD1 protein levels and increased the 14-3-3 protein levels and P38MAPK, mTOR, P70S6k, and 4EBP1 phosphorylation. Moreover, exercise increased the REDD1/14-3-3 association in the heart. Our results indicate that the phospho-P38MAPK, REDD1, and 14-3-3 protein levels were reduced in the myocardium of obese rats and that physical exercise increased the protein levels of these molecules.

[Comparative value of B-type natriuretic peptide and serum albumin concentration in the prediction of in-hospital mortality in elderly patients admitted for acute severe heart failure]. / Valeur prédictive comparée de mortalité hospitalière du peptide natriurétique de type B et de l'albuminémie chez le sujet âgé hospitalisé pour insuffisance cardiaque aiguë sévère.

OBJECTIVE: To address the clinical relevance of serum albumin and B-type natriuretic peptide (BNP) concentration in the prediction of in-hospital death in elderly patients with acute severe heart failure. PATIENTS AND METHODS: Seventy-four consecutive patients >70 years of age admitted for acute heart failure in NYHA class IV were prospectively included. BNP concentration was measured on admission and serum albumin concentration after clinical stabilization. RESULTS: Mean age was 86.6+/-5.7 years. Sixty-five percent of patients had a normal left ventricular ejection fraction. Eighteen patients died during the in-hospital stay. Those patients who died were older, had higher blood urea nitrogen and BNP concentration, had lower systolic blood pressure and serum albumin concentration than patients who survived. Heart rate, rhythm, left ventricular ejection fraction, serum creatinine and hemoglobin did not differ according to outcome. By multivariate analysis, albumin (p=0.0017), BNP (p=0.016) and age (p=0.03) were independent predictors of in-hospital death. Serum troponin I measured on admission in 71 patients was predictive of in-hospital death (p=0.01), as well as serum total cholesterol measured after stabilization in 66 patients (p=0.004). However, these two variables no longer predicted outcome in multivariate models, unlike serum albumin and BNP. CONCLUSION: Serum albumin and BNP offer independent, additional information for the prediction of in-hospital death in elderly patient with acute severe heart failure regardless of left ventricular ejection fraction.

[Usefulness of B-type natriuretic peptide (BNP) for the diagnosis of new-onset heart failure with a preserved left ventricular systolic function in longstanding hypertensive patients with acute dyspnea]. / Apport du peptide natriurétique de type B dans le primo-diagnostic d'insuffisance cardiaque à fonction systolique preservée chez le patient hypertendu souffrant de dyspnée aiguë.

BACKGROUND: B-type natriuretic peptide (BNP) has been largely validated in the etiologic diagnosis of acute dyspnea. Nevertheless, its reliability in the setting of a preserved left ventricular systolic function (ejection fraction >50%) has not been adequately established. OBJECTIVE: the study addressed the usefulness of BNP in the diagnosis of new-onset heart failure with a preserved systolic function in hypertensive patients hospitalized for acute dyspnea. METHODS: 59 consecutive hypertensive patients without history of heart failure and coronary disease were included. BNP was measured at presentation with the Triage system. Noninvasive estimation of left ventricular filling pressures by bedside tissue Doppler echocardiography at presentation was incorporated in the diagnostic criteria. RESULTS: the 30 patients with heart failure were not significantly different from the 29 patients with noncardiac cause of acute dyspnea regarding age, gender, body mass index and ejection fraction. Median levels of BNP were significantly higher in heart failure (447 [245-644] versus 87 [43-139] pg/mL). By multivariate logistic regression analysis, BNP (odds ratio of 44, [3.6-531], p=0.003) provided independent and incremental diagnostic information over the clinical score of Boston criteria (2.25, [1.3-3.9], p=0.0037). A BNP value of >142 pg/mL (area under the ROC curve of 0.89, p<0.0001) was 93 sensitive and 79% specific for the diagnosis of heart failure in this setting. CONCLUSION: BNP is a reliable biomarker of new-onset heart failure with a preserved systolic function in hypertensive patients, in particular older, hospitalized for acute dyspnea and can be safely integrated in the diagnostic strategy.

[Prognostic value of BNP for hospital mortality in elderly subjects hospitalised for acute diastolic cardiac failure]. / Valeur pronostique du BNP pour la mortalité hospitalière chez le sujet agé hospitalisé pour insuffisance cardiaque diastolique aiguë.

The aim of this study was to evaluate the prognostic value of BNP in elderly patients hospitalised for acute diastolic cardiac failure. 108 consecutive subjects were included, aged at least 70 years old, hospitalised for isolated acute diastolic cardiac failure. All of them had a left ventricular ejection fraction > or = 50% and evidence of diastolic dysfunction on echocardiography performed shortly after admission. The plasma BNP concentration measured in the emergency department on admission was >100 pg/ml in all of the patients except five. It was positively correlated with age (R = 0.29, p = 0.002), with the plasma creatinine level (R = 0.37, p < 0.0001) and the plasma urea level (R = 0.41, p < 0.0001). On univariate analysis, compared to the patients who survived, the 20 patients who died before discharge were significantly older (88.6 versus 84.4 years, p = 0.01), and were more often residents of a care home (60 versus 31%. p = 0.02), had a lower systolic blood pressure on admission (127 +/- 33 versus 154 +/- 30 mm Hg), a higher plasma urea level (16.8 +/- 12 versus 8.9 +/- 5 mmol/l, p = 0.002) and a higher BNP (median = 1290 pg/ml, interquartile range: 721, 3026 pg/ml versus 430 pg/ml, interquartile range: 243, 886 pg/ml). On multivariate analysis, the only factors that remained significantly associated with mortality were the BNP levels (p = 0.005) and the systolic blood pressure (p = 0.01). The negative predictive value of a BNP level < 631 pg/ml (median) for death was 94% (95% confidence interval: 91 to 97%). We conclude that BNP does have an independent prognostic value for in-hospital death in elderly subjects with acute diastolic cardiac failure.

[Novel Doppler indexes of estimation of pulmonary capillary pressure: influence of age, feasibility in the acute setting and reproducibility]. / Nouveaux indices doppler d'estimation de la pression capillaire pulmonaire: influence de l'âge, faisabilité en situation aiguë et reproductibilité.

BACKGROUND: The Doppler indexes E/Vp, E/Ea, 1000/(2 x IRT + Vp), 1000/(2 x IRT + Ea) and DTd (E: peak E mitral velocity; Vp: flow propagation velocity by color M-mode; Ea: peak early diastolic velocity at lateral mitral annulus by tissue Doppler; IRT: isovolumic relaxation time; DTd: deceleration time of the pulmonary venous diastolic wave) have been proposed for the non-invasive prediction of left ventricular filling pressures. However, the influence of age, the feasibility in acute setting and the reproducibility of these Doppler indexes have never been simultaneously investigated. OBJECTIVE: The present study was conducted to evaluate the influence of age in 56 healthy subjects (57 +/- 20 years of age), the feasibility in 40 critically ill patients (72 +/- 13 years of age; 21 with decompensated heart failure) and the reproducibility in 15 patients. RESULTS: Only the indexes E/Vp (R = 0.37, P = 0.005) and E/Ea (R = 0.72, P < 0.001) were correlated with age. The feasibility was 92, 90, 72, 72 and 45% for E/Ea, 1000/(2 x IRT + Ea), E/Vp, 1000/(2 x IRT +Vp) and DTd, respectively. The best reproducibility was observed for the Doppler parameters E and Ea. CONCLUSION: Despite it is influenced by age, E/Ea appears to be the most useful index for predicting left ventricular filling pressures routinely.

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behçet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behçet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first anti-tumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behçet disease.

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first antitumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behet disease. (Eur J Ophthalmol 2004; 14: #-8).

[Value of Doppler indices of diastolic left ventricular dysfunction in acute cardiac insufficiency]. / Valeur des indices Doppler de dysfonction ventriculaire gauche diastolique dans l'insuffisance cardiaque aiguë.

OBJECTIVE: To examine the prevalence of diastolic dysfunction by Doppler study in acute cardiac failure. CONTEXT: A recent study showed that diastolic dysfunction is constant in stable cardiac failure with preserved systolic function and suggested that its measurement was not necessary for the diagnosis of diastolic cardiac failure, but the prevalence of diastolic dysfunction in acute cardiac failure is not known. METHOD: The mitral and pulmonary venous profiles, the propagation velocity Vp of colour filling flow, and the lateral velocity Ea of the mitral ring in DTI were studied at the time of treatment initiation in 28 patients in sinus rhythm and in acute cardiac failure (11 NYHA IV and 17 with pulmonary oedema), of whom 18 had an ejection fraction greater than 50%. RESULTS: Diastolic dysfunction was present in the combined study of mitral and pulmonary profiles in 95% and 100% respectively of patients in cardiac failure with preserved systolic function and altered systolic function, and Vp < 45 and/or Ea < 8 cm/s was observed in 55% and 100% respectively of these patients. At respective pathological threshold values of 1.5 and 10, the combined indices E/Vp and E/Ea were concordant with the evaluation of filling pressures in 83% of patients with preserved systolic function and 100% of the systolic cardiac failure cases. CONCLUSION: Diastolic dysfunction is almost constant in acute cardiac failure independently of the ejection fraction value. However, normal values of Ea and Vp do not exclude the diagnosis of diastolic cardiac insufficiency in the acute situation.

[Silent ischemia and acute cardiac insufficiency with normal systolic function: diagnostic value of troponin I measurement]. / Ischémie silencieuse et insuffisance cardiaque aiguë à fonction systolique conservée: intérêt diagnostique du dosage de la troponine I.

The physiopathological mechanisms resulting in increased left ventricular pressures in acute cardiac failure with normal systolic function are not well understood. Although coronary artery disease is commonly associated with acute episodes, the diagnostic value of troponin I measurement and the prevalence of ischaemia as the predisposing factor are not known. Twenty coronary patients (mean age 77 +/- 9 years) in acute cardiac failure with left ventricular ejection fractions of 50% or over and without angina, were studied retrospectively. The diagnostic value of troponin I (cTnI, AxSYM, method) was assessed by comparing with a control group of 16 acute cardiac failure patients without coronary disease. The frequency of hypertension and diabetes in the coronary group was 50 and 45% respectively. At the time of investigation, the pulmonary capillary and systemic arterial pressures were comparable in the coronary patients irrespective of the cTnl value. At threshold levels of 0.5 microgram/l, cTnl had a specificity of 100% and confirmed ischaemia in 60% of the coronary patients. Ischaemia was the commonest predisposing factor for increased cardiac pressures. Over a 268 +/- 101 days follow-up period, half the coronary patients were readmitted for acute cardiac failure and a third of them died. The authors conclude that silent ischaemia is a common predisposing factor for acute cardiac failure in coronary patients with normal systolic function and troponin I measurement is a useful diagnostic help.

[Study of non-invasive hemodynamic parameters in pulmonary edema: hypoalbuminemia is a factor frequently associated with acute diastolic cardiac insufficiency]. / Etude des paramètres hémodynamiques non invasifs dans l'oedème pulmonaire: l'hypo-albuminémie est un facteur favorisant fréquent de l'insuffisance cardiaque diastolique aiguë.

SUBJECT: A critical diminution of the gradient between plasma oncotic pressure (PO) and pulmonary capillary pressure (PCP) is the origin of the formation of haemodynamic pulmonary oedema (OAP), but the respective contribution of these two haemodynamic forces as a function of the type of cardiac insufficiency is not known. METHOD: 74 cases of OAP were included (78 +/- 15 years old, 43 diastolic defined by an ejection fraction greater than 45%, and 31 systolic), and 33 control subjects. PO and PCP were calculated respectively from total protein and albumin serum levels, and from transthoracic echocardiography with the new Doppler indices using refilling flow propagation speed in colour TM or the study of pulmonary venous flow, at the start of treatment. RESULTS: The gradient was very significantly diminished in those with diastolic and systolic cardiac insufficiency compared to the control group (p < 0.001), with no difference between the two types of OAP. An elevation of PCP > or = 18 mm Hg was the principal haemodynamic factor in the critical diminution of the gradient in the systolic group and in the diastolic group with ischaemic or valvular cardiopathy. In parallel with the elevation in PCP was a state of plasma hypo-oncocity < or = 18 mm Hg, consecutive with a significant diminution of albuminaemia, contributing to the critical diminution of the gradient in 41% of diastolic cases versus 3% of systolic cases. CONCLUSION: Hypo-albuminaemia is a factor frequently favouring acute diastolic cardiac insufficiency in elderly subjects and must be sought systematically.

[Precipitating factors associated with diastolic heart failure in the elderly]. / Facteurs aggravants associés à l'insuffisance cardiaque à fonction systolique conservée chez le sujet âgé.

BACKGROUND: Beside basal myocardial dysfunction, acute heart failure involves associated factors, which increase pulmonary capillary pressure or decrease colloid osmotic pressure. The aim of this study was to evaluate the prevalence of these precipitating factors in a population presenting with acute heart failure with preserved left ventricular systolic function. METHODS: Forty-eight patients (25 men, 78 +/- 10 years) presenting pulmonary edema with a left ventricular ejection fraction > 45% were included. All had a Doppler echocardiography at the time of intravenous loop diuretics initiation. Patients with severe valve disease or symptomatic coronary disease were excluded. RESULTS: A history of heart failure, coronary disease, hypertension and diabetes was present in 62%, 42%, 64% and 33% of patients, respectively. On admission, mean left ventricular ejection fraction was 61 +/- 9% and 79% of patients had critical elevation in Doppler filling pressures. Associated factors were renal failure (creatinine clearance < 30 ml/min) in 33% patients, silent myocardial ischemia (troponin I > 0.5 ng/ml) in 31%, atrial fibrillation in 29%, high systolic blood pressure (> or = 160 mmHg) in 27%, major sepsis in 25%, severe hypoalbuminemia (< or = 2.5 g/dl) in 23%, and severe anemia (< 10 g/dl) in 17%, respectively. Four patients had no aggravating factor, whereas 34 and 10 patients had 1-2 and 3-4 associated factors, respectively. CONCLUSION: Besides diastolic dysfunction, factors leading to a critical decrease in the oncotic pressure such as pulmonary capillary pressure gradient are found in most of the elderly patients presenting acute diastolic heart failure and must be checked systematically.

[Usefulness in clinical practice of noninvasive measurement of colloids osmotic pressure-capillary pulmonary pressure gradient in the management of acute dyspnea]. / Intérêt en pratique clinique de la mesure non invasive du gradient pression oncotique-pression capillaire pulmonaire dans la prise en charge d'une dyspnée aiguë.

BACKGROUND: Increased pulmonary capillary pressure (PAWP) and decreased serum colloid osmotic pressure (COP) are important factors in pulmonary edema (PE) formation. The aim of this study was to evaluate the clinical usefulness of noninvasive determination of COP, PAWP and COP-PAWP gradient in patients with acute dyspnea. METHODS: Thirty four patients presenting with PE, 19 with preserved left ventricular systolic function (Ia) and 15 with depressed systolic function (Ib), and 26 patients presenting with acute pulmonary diseases (II) were enrolled. COP was estimated using Landis and Pappenheimer formula (COP = 2.1 x P + 0.16 x P2 + 0.009 x P3, P: serum total protein concentration). PAWP was measured by transthoracic Doppler echocardiography using E/Vp and 1000/(2 x IPT + Vp) Doppler indexes. RESULTS: The mean value of the gradient was 0.5 +/- 5, 1.7 +/- 3.4 and 10.4 +/- 4.7 mmHg in Ia, Ib and II respectively (P < 0.001 Ia and Ib vs II). PAWP was higher in Ia and Ib than in II (P < 0.001). However, hypoalbuminemia with COP < or = 18 mmHg was observed in 63% of patients in Ia as compared to those in Ib (7%) and II (8%). CONCLUSIONS: Severe hypoalbuminemia frequently contributes to PE formation in the presence of normal left ventricular systolic function. A COP-PAWP gradient value lower than 6 mmHg is highly predictive of the diagnosis of acute heart failure in these patients presenting with acute dyspnea.

[Usefulness of Doppler echocardiography in the diagnosis of acute diastolic heart failure in the elderly]. / Apport de l'échocardiographie Doppler dans le diagnostic de l'insuffisance cardiaque aiguë à fonction systolique conservée du sujet âgé.

PURPOSE: To evaluate the clinical usefulness of the determination of Doppler mitral inflow pattern and new combined indices using colour M mode velocity flow propagation (Vp) in the diagnosis of acute diastolic heart failure in the elderly. METHODS: Total serum protein concentration (P, g/l) and E/A, E/Vp and 1000/(2 x IRT + Vp) Doppler indices (E and A: mitral inflow peak velocities; IRT: isovolumic relaxation time) were measured at the time of therapy initiation in 94 patients with left ventricular ejection fraction > 50% (78 +/- 13 years), 56 with pulmonary edema and 38 patients with acute respiratory disease. RESULTS: The feasibility was 73, 90 and 89% for E/A, E/Vp and 1000/(2 x IRT + Vp) respectively. The sensitivity, specificity and accuracy were 94-56-72%, 84-86-85% and 92-86-89% for E/A > or = 1, E/Vp > or = 2 and 1000/(2 x IRT + Vp) > or = 6 respectively in the diagnosis of pulmonary edema in patients with normal serum colloid osmotic pressure defined by P > or = 60 g/l, and 41-50-43%, 37-86-50% and 22-100-42% in patients with low colloid osmotic pressure (P < 60 g/l). CONCLUSIONS: The mitral inflow measurement is limited in most of cases of acute diastolic heart failure in the elderly by confounding factors such as atrial fibrillation and normalised pattern. New combined Doppler indices are useful in these patients, however, their value must be interpreted according to the serum colloid osmotic status estimated by total serum protein concentration.

Ocular haemodynamics and nitric oxide in normal pressure glaucoma.

The authors studied the ocular haemodynamics by means of the Color Doppler Imaging (CDI) technique and the levels of cyclic guanosine monophosphate (cGMP), the intracellular mediator of NO action in plasma and the aqueous humour in a Normal Pressure Glaucoma group and in a normal group. They found significant alterations of both the velocities, systolic and diastolic, in the Ophthalmic Artery and lower cGMP levels in NPGs than in the controls. These data suggest that a disorder of NO regulation processes might be involved in blood supply to the optic nerve and in aqueous humour outflow.