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Background Hypertrophic cardiomyopathy (HCM) is a common genetic disease that may cause left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden death. Recent studies have shown a high prevalence of OSA among patients with HCM. Because the hemodynamics in patients with LVOT obstruction are unstable and depend on the loading conditions of the heart, we evaluated the acute effects of CPAP on hemodynamics and cardiac performance in patients with HCM. Methods We studied 26 stable patients with HCM divided into nonobstructive HCM (n = 12) and obstructive HCM (n = 14) groups (LVOT gradient pressure lower or higher than 30 mm Hg, respectively). Patients in the supine position while awake were continuously monitored with beat-to-beat BP measurements and electrocardiography. Two-dimensional echocardiography was performed at rest (baseline) and after 20 min of nasal CPAP at 1.5 cm H 2 O and 10 cm H 2 O, which was applied in a random order interposed by 10 min without CPAP. Results BP, cardiac output, stroke volume, heart rate, left ventricular ejection fraction, and LVOT gradient did not change during the study period in either group. CPAP at 10 cm H 2 O decreased right atrial size and right ventricular relaxation in all patients. It also decreased left atrial volume significantly and decreased right ventricular outflow acceleration time, suggesting an increase in pulmonary artery pressure in patients with obstructive HCM. Conclusions The acute application of CPAP is apparently safe in patients with HCM, because CPAP does not lead to hemodynamic compromise. Long-term studies in patients with HCM and sleep apnea and nocturnal CPAP are warranted. Trial Registry ClinicalTrials.gov; No. NCT01631006 ; URL: www.clinicaltrials.gov

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.

Previous studies show that angiotensin II (AngII) mediates muscle wasting. In chronic heart failure (CHF), exercise training reduces AngII and improves skeletal myopathy. Unknown is whether the improvement in skeletal myopathy in CHF provoked by exercise training depends on AngII reduction. Thus, we studied the effects of exercise training on muscle ubiquitin-proteasome pathway in CHF rats submitted to an AngII clamp (osmotic minipump). Male Wistar rats underwent coronary artery ligation for CHF induction. At fourth week of surgery, the CHF rats were divided into three groups: 1) Untrained; 2) exercise-trained and 3) exercise-trained with AngII. Exercise training was conducted on a treadmill 60min/day, 5 days/wk at 60% VO2max during 8wk. Exercise training reduced E3a, Atrogin and MuRF mRNA expression (RT-PCR), carbonylated and ubiquitinated proteins (Western Blot), and 26S proteasomal activity (Fluorimetry) in plantaris muscle of CHF rats. AngII infusion, set at the same levels of untrained rats, restrain...

BACKGROUND: Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. METHODS/MAIN RESULTS: Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. CONCLUSIONS: Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal muscle.

BACKGROUND The presence of asymptomatic left ventricular diastolic dysfunction (LVDD) in hypertensive patients can be associated with the development of cardiac events. The increase in sympathetic activity may be 1 of the mechanisms that predisposes to this outcome. In this study, we analyzed 2 hypotheses: (i) whether sympathetic activity is higher in the presence of LVDD, independent of blood pressure control and (ii) whether different classes of LVDD have a different effect on sympathetic activity. METHODS After analyzing left ventricular function using echo Doppler cardiography, 45 hypertensive patients receiving treatment were allocated into 3 groups: normal function (LV-NF, n = 15), impaired relaxation (LV-IR, n = 15), and pseudonormal or restrictive (LV-P/R, n = 15). An age-, sex-, and body mass index-matched control group of normotensive volunteers (N, n = 14) was included. Muscle sympathetic nerve activity (MSNA), heart rate, and systolic blood pressure variabilities and baroreflex sensitivity were evaluated while the patient was in a supine position. RESULTS Blood pressure and antihypertensive drug use were similar among the hypertensive groups. The LV-IR and LV-P/R groups had similar MSNA (33±1 and 32±1 bursts/min, respectively), which was significantly higher than that of the LV-NF and N groups (26±3 and 15±2 bursts/min, respectively). The LV-IR and LV-P/R groups had significantly higher LF-systolic blood pressure variability and significantly lower baroreflex sensitivity compared with the N group. CONCLUSIONS The presence of asymptomatic LVDD is associated with increased MSNA, independent of blood pressure control. The sympathetic hyperactivity associated with LVDD is similar in the different patterns of LVDD studied.