Early ovarian hormone deprivation increases cardiac contractility in old female rats-Role of physical training.

OBJECTIVES: We investigated the effects of early ovarian hormones deprivation on morphology and cardiac function and the effects of aerobic training on these parameters, in old rats. METHODS: Female Wistar rats (N = 48) were divided into two groups, at 10 weeks of life: early ovarian hormones deprivation by ovariectomy (OVX; N = 24) and sham (SHAM; N = 24). Between weeks 62 and 82, 12 animals of each group underwent aerobic training (OVX-T and SHAM-T, N = 12). At the end of week 82, all were evaluated by echocardiography, cardiac function (Langendorff technique) and cardiac ß-adrenergic receptor expression quantification. RESULTS: Echocardiography showed slight changes in morphology between OVX and SHAM groups. OVX group (Δ = 101 ±â€¯4.7 mmHg) showed higher values for maximal left intraventricular pressure in response to dobutamine, when compared to SHAM group (Δ = 55 ±â€¯11.8 mmHg). Both OVX-T (Δ = 70 ±â€¯4.0 mmHg) and SHAM-T (Δ = 22 ±â€¯6.6 mmHg) groups showed a reduction in this response. While, ß-adrenergic receptor expression was not different between the untrained groups, SHAM-T (0.23 ±â€¯0.02 AU) and OVX-T (0.29 ±â€¯0.01 AU), showed decreased expression of these receptors. CONCLUSION: Early ovarian hormones deprivation associated with aging, promotes discrete changes in cardiac morphology and increasing cardiac contractility. Aerobic training decreases ß-adrenergic receptors expression, influencing the cardiac contractility.

Activation of Both the Calpain and Ubiquitin-Proteasome Systems Contributes to Septic Cardiomyopathy through Dystrophin Loss/Disruption and mTOR Inhibition.

Cardiac dysfunction caused by the impairment of myocardial contractility has been recognized as an important factor contributing to the high mortality in sepsis. Calpain activation in the heart takes place in response to increased intracellular calcium influx resulting in proteolysis of structural and contractile proteins with subsequent myocardial dysfunction. The purpose of the present study was to test the hypothesis that increased levels of calpain in the septic heart leads to disruption of structural and contractile proteins and that administration of calpain inhibitor-1 (N-acetyl-leucinyl-leucinyl-norleucinal (ALLN)) after sepsis induced by cecal ligation and puncture prevents cardiac protein degradation. We also tested the hypothesis that calpain plays a role in the modulation of protein synthesis/degradation through the activation of proteasome-dependent proteolysis and inhibition of the mTOR pathway. Severe sepsis significantly increased heart calpain-1 levels and promoted ubiquitin and Pa28ß over-expression with a reduction in the mTOR levels. In addition, sepsis reduced the expression of structural proteins dystrophin and ß-dystroglycan as well as the contractile proteins actin and myosin. ALLN administration prevented sepsis-induced increases in calpain and ubiquitin levels in the heart, which resulted in decreased of structural and contractile proteins degradation and basal mTOR expression levels were re-established. Our results support the concept that increased calpain concentrations may be part of an important mechanism of sepsis-induced cardiac muscle proteolysis.

Sepsis-induced acute kidney injury: biomarkers for diagnosis

Sepsis is a major global health problem leading to the increased incidence of death in intensive care units. In recent years, despite technological advances, the number of cases has grown significantly. Among the main complications presented by septic patients, acute renal dysfunction is largely responsible for the high mortality rate. Initially, the reduction of renal function is associated with focal tubular injury with preserved glomerular morphology and systemic hemodynamic alterations. During sepsis development, the progressive decrease in urinary volume and reduction of the glomerular filtration rate associated with increased serum levels of urea and creatinine are considered classic markers of severe kidney injury. Despite the valuable role of these serum markers regarding renal function, these data provide an incomplete scenario of the patient, since many renal disorders may occur in individuals with increased plasma concentrations of urea and creatinine. Taking into account the important role of systemic inflammatory processes in the development of acute kidney injury induced by sepsis, the search for new markers presenting high sensitivity and specificity capable of detecting early renal injury is still necessary. Thus, the present review summarizes important aspects of pathophysiology of acute kidney dysfunction induced by sepsis and presents an updated view of possible new biomarkers associated with the development of acute kidney injury. Understanding these markers allows important advances leading to new therapeutic approaches, indicating a new horizon in the diagnosis and treatment of acute kidney injury in sepsis