Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system.

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain ß-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.

Yoga and breathing technique training in patients with heart failure and preserved ejection fraction: study protocol for a randomized clinical trial.

BACKGROUND: Current therapies for heart failure (HF) are followed by strategies to improve quality of life and exercise tolerance, besides reducing morbidity and mortality. Some HF patients present changes in the musculoskeletal system and inspiratory muscle weakness, which may be restored by inspiratory muscle training, thus increasing respiratory muscle strength and endurance, maximal oxygen uptake (VO2), functional capacity, respiratory responses to exercise, and quality of life. Yoga therapies have been shown to improve quality of life, inflammatory markers, and peak VO2 mostly in HF patients with a reduced ejection fraction. However, the effect of different yoga breathing techniques in patients showing HF with a preserved ejection fraction (HFpEF) remain to be assessed. METHODS/DESIGN: A PROBE (prospective randomized open blinded end-point) parallel-group trial will be conducted at two specialized HF clinics. Adult patients previously diagnosed with HFpEF will be included. After signing informed consent and performing a pre-test intervention, patients will be randomized into three groups and provided with either (1) active yoga breathing techniques; (2) passive yoga breathing techniques (pranayama); or and (3) control (standard pharmacological treatment). Follow-up will last 8 weeks (16 sessions). The post-intervention tests will be performed at the end of the intervention period for analysis of outcomes. Interventions will occur continuously according to patients' enrollment. The main outcome is respiratory muscular resistance. A total of 33 enrolled patients are expected. The present protocol followed the SPIRIT guidelines and fulfilled the SPIRIT checklist. DISCUSSION: This trial is probably the first to assess the effects of a non-pharmacological intervention, namely yoga and specific breathing techniques, to improve cardiorespiratory function, autonomic system, and quality of life in patients with HFpEF. TRIAL REGISTRATION: REBEC Identifier: RBR-64mbnx (August 19, 2012). Clinical Trials Register: NCT03028168 . Registered on 16 January 2017).

Insuficiência cardíaca - fisiopatologia atual e implicações terapêuticas / Heart failure - current pathophysiology and terapeutic implications

Conhecer a fisiopatologia da insuficiência cardíaca propiciou uma evolução terapêutica em seu manejo, que se traduziu em melhora de desfechos clínicos relevantes, incluindo redução da mortalidade. O conceito do remodelamento ventricular, associado à ativação neuro-humoral descrita inicialmente, via ativação do sistema renina-angiotensina-aldosterona, e posteriormente via ativação simpática, levou ao uso de inibidores da ECA e de betabloqueadores, respectivamente, que mudaram o curso da história da insuficiência cardíaca. Ainda na categoria farmacológica, mais recentemente a modulação da rota da neprilisina, através do uso do composto sacubitril/valsartan, trouxe impacto adicional de redução de mortalidade em pacientes com insuficiência cardíaca. Por fim, dispositivos que também interfiram no processo de remodelamento ventricular, como marcapassos de ressincronização biventricular, demonstraram benefícios clínicos significativos. Novos alvos moleculares, microRNAs ou moléculas de sinalização intracelular, devem crescer como potenciais áreas de investigação na progressão da doença e, potencialmente, se transformarem em alvos terapêuticos

Knowledge of the pathophysiology of heart failure has led to a therapeutic evolution in its management that has resulted in improved clinical outcomes, including a reduction in mortality. The concept of ventricular remodeling associated with neurohumoral activation, initially described via activation of the renin-angiotensin-aldosterone system and later, via sympathetic activation, led to the use of ACE inhibitors and beta blockers, respectively, altering the course of history of heart failure. Also in the pharmacological category, more recently, modulation of the neprilysin route, through the use of the compound sacubitril/valsartan, brought additional impacts in reducing mortality in patients with heart failure. Finally, devices that also interfere in the process of ventricular remodeling, such as biventricular resynchronization pacemakers, have demonstrated significant clinical benefits. New molecular targets, microRNAs, or intracellular signaling molecules should increase as potential areas of research on disease progression, and could potentially become therapeutic targets

Ghrelin and leptin modulate the feeding behaviour of the hawksbill turtle Eretmochelys imbricata during nesting season.

Female sea turtles have rarely been observed foraging during the nesting season. This suggests that prior to their migration to nesting beaches the females must store sufficient energy and nutrients at their foraging grounds and must be physiologically capable of undergoing months without feeding. Leptin (an appetite-suppressing protein) and ghrelin (a hunger-stimulating peptide) affect body weight by influencing energy intake in all vertebrates. We investigated the levels of these hormones and other physiological and nutritional parameters in nesting hawksbill sea turtles in Rio Grande do Norte State, Brazil, by collecting consecutive blood samples from 41 turtles during the 2010-2011 and 2011-2012 reproductive seasons. We found that levels of serum leptin decreased over the nesting season, which potentially relaxed suppression of food intake and stimulated females to begin foraging either during or after the post-nesting migration. Concurrently, we recorded an increasing trend in ghrelin, which may have stimulated food intake towards the end of the nesting season. Both findings are consistent with the prediction that post-nesting females will begin to forage, either during or immediately after their post-nesting migration. We observed no seasonal trend for other physiological parameters (values of packed cell volume and serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, low-density lipoprotein, and high-density lipoprotein). The observed downward trends in general serum biochemistry levels were probably due to the physiological challenge of vitellogenesis and nesting in addition to limited energy resources and probable fasting.