[Show abstract][Hide abstract] ABSTRACT: Background:
Psammomys obesus gerbils are particularly prone to develop diabetes and obesity after brief period of abundant food intake. A hypercaloric high fat diet has been shown to affect cardiac function. Here, we sought to determine whether a short period of high fat feeding might alter myocardial structure and expression of calcium handling proteins in this particular strain of gerbils.
Twenty Psammomys obesus gerbils were randomly assigned to receive a normal plant diet (controls) or a high fat diet. At baseline and 16-week later, body weight, plasma biochemical parameters (including lipid and carbohydrate levels) were evaluated. Myocardial samples were collected for pathobiological evaluation.
Sixteen-week high fat dieting resulted in body weight gain and hyperlipidemia, while levels of carbohydrates remained unchanged. At myocardial level, high fat diet induced structural disorganization, including cardiomyocyte hypertrophy, lipid accumulation, interstitial and perivascular fibrosis and increased number of infiltrating neutrophils. Myocardial expressions of pro-apoptotic Bax-to-Bcl-2 ratio, pro-inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α], intercellular (ICAM1) and vascular adhesion molecules (VCAM1) increased, while gene encoding cardiac muscle protein, the alpha myosin heavy polypeptide (MYH6), was downregulated. Myocardial expressions of sarco(endo)plasmic calcium-ATPase (SERCA2) and voltage-dependent calcium channel (Cacna1c) decreased, while protein kinase A (PKA) and calcium-calmodulin-dependent protein kinase (CaMK2D) expressions increased. Myocardial expressions of ryanodine receptor, phospholamban and sodium/calcium exchanger (Slc8a1) did not change.
We conclude that a relative short period of high fat diet in Psammomys obesus results in severe alterations of cardiac structure, activation of inflammatory and apoptotic processes, and altered expression of calcium-cycling determinants.
[Show abstract][Hide abstract] ABSTRACT: Background:
Patients with pulmonary arterial hypertension (PAH) and with heart failure (HF) have increased ventilatory responses to exercise in proportion to disease severity. Exercise-associated oscillatory ventilation (EOV) predicts poor outcome in HF. Whether EOV occurs in PAH is unknown.
We analyzed the initial cardiopulmonary exercise tests (CPETs) and right heart catheterization data of 109 patients with PAH and in 107 patients with HF consecutively referred to our center.
The PAH patients were aged 54±16years and their NYHA functional class was 2.8±0.5. The HF patients were aged 53±13years and NYHA 2.4±0.6. Hemodynamic data were obtained in only 36 of them. The patients with PAH compared to those with HF had a lower peak VO2 (13±5 vs 17±5mL/kg/min, p<0.001) and a higher ventilatory equivalent for CO2 (VE/VCO2) slope (55±21 vs 34±7, p<0.001). Mean pulmonary artery pressure was higher (50±10 vs 29±11mmHg) and wedge pressure lower (10±3 vs 19±5mmHg) in PAH patients, but cardiac output was not different (4.0±1.3 vs 4.2±1.2L/min). EOV was present in 22 patients (21%) with HF and in no patient with PAH.
Patients with PAH compared to HF with slightly better functional class have a lower aerobic exercise capacity and higher ventilatory responses, but no EOV. An increase in pulmonary artery wedge pressure rather than a low cardiac output may be necessary condition of EOV in HF.
No preview · Article · Sep 2015 · International journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: Right ventricular function is a major determinant of symptomatology and prognosis in severe pulmonary hypertension. The diagnosis of right heart failure rests on a clinical approach with invasive and noninvasive measurements. Magnetic resonance and echocardiographic imaging of the right ventricle is of prognostic relevance. The gold standard of right ventricular function is the ratio of end-systolic to arterial elastances determined from synchronized volume and pressure measurements. Pressure measurements can be obtained during a right heart catheterization and volume measurements by integration of Doppler pulmonary flow-velocity, magnetic resonance imaging, or, more recently, three-dimensional echocardiography. Imaging also informs about regional function and derived estimates of dyssynchrony and asynchrony. Modern imaging with 3D echocardiography and magnetic resonance aims at improved assessment of regional function and right ventriculo-arterial coupling to assist in the evaluation and prognostication of severe pulmonary hypertension.
No preview · Article · May 2015 · Current Hypertension Reports
[Show abstract][Hide abstract] ABSTRACT: Hypoxic exposure depresses myocardial contractility in vitro, but has been associated with indices of increased cardiac performance in intact animals and in humans, possibly related to sympathetic nervous system activation. We explored left ventricular (LV) function using speckle tracking echocardiography and sympathetic tone by spectral analysis of heart rate variability (HRV) in recently acclimatized lowlanders versus adapted or maladapted highlanders at high altitude. Twenty-six recently acclimatized lowlanders, 14 healthy highlanders and 12 highlanders with chronic mountain sickness (CMS) were studied. Control measurements at sea level were also obtained in the lowlanders. Altitude exposure in the lowlanders was associated with slightly increased blood pressure, decreased LV volumes and decreased longitudinal strain with a trend to increased prevalence of post-systolic shortening (p = 0.06), whereas the low frequency/high frequency (LF/HF) ratio increased (1.62 ± 0.81 vs. 5.08 ± 4.13, p < 0.05) indicating sympathetic activation. Highlanders had a similarly raised LF/HF ratio, but no alteration in LV deformation. Highlanders with CMS had no change in LV deformation, no significant increase in LF/HF, but decreased global HRV still suggestive of increased sympathetic tone, and lower mitral E/A ratio compared to healthy highlanders. Short-term altitude exposure in lowlanders alters indices of LV systolic function and increases sympathetic nervous system tone. Life-long altitude exposure in highlanders is associated with similar sympathetic hyperactivity, but preserved parameters of LV function, whereas diastolic function may be altered in those with CMS. Altered LV systolic function in recently acclimatized lowlanders may be explained by combined effects of hypoxia and changes in loading conditions.
Full-text · Article · Feb 2015 · The International Journal of Cardiovascular Imaging