The NAD ⁺ precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.

Cardiovascular diseases are the main cause of death in the world and are often associated with the occurrence of arrhythmias due to disruption of myocardial electrical integrity. Pathologies involving dysfunction of the specialized cardiac excitatory/conductive tissue are also common and constitute an added source of morbidity and mortality since current standard therapies withstand a great number of limitations. As electrical integrity is essential for a well-functioning heart, innovative strategies have been bioengineered to improve heart conduction and/or promote myocardial repair, based on: (1) gene and/or cell delivery; or (2) conductive biomaterials as tools for cardiac tissue engineering. Herein we aim to review thestate-of-artin the area, while briefly describing the biological principles underlying the heart electrical/conduction system and how this system can be disrupted in heart disease. Suggestions regarding targets for future studies are also presented.

Myocardial fluid homeostasis relies on a complex interplay between microvascular filtration, interstitial hydration, cardiomyocyte water uptake and lymphatic removal. Dysregulation of one or more of these mechanisms may result in myocardial oedema. Interstitial and intracellular fluid accumulation disrupts myocardial architecture, intercellular communication, and metabolic pathways, decreasing contractility and increasing myocardial stiffness. The widespread use of cardiac magnetic resonance enabled the identification of myocardial oedema as a clinically relevant imaging finding with prognostic implications in several types of heart failure. Furthermore, growing experimental evidence has contributed to a better understanding of the physical and molecular interactions in the microvascular barrier, myocardial interstitium and lymphatics and how they might be disrupted in heart failure. In this review, we summarize current knowledge on the factors controlling myocardial water balance in the healthy and failing heart and pinpoint the new potential therapeutic avenues.

Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged τ and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present.

Septic cardiomyopathy is an increasingly relevant topic in clinical management of septic shock. However, pathophysiological mechanisms and long-term consequences of sepsis-induced myocardial injury are still poorly understood. Herein, new clinical and histological evidence is provided suggesting an association of myocardial edema formation with tissue injury and subsequent remodeling in septic shock patients. This preliminary data supports myocardial edema as a potentially relevant and largely unexplored mechanism of human septic cardiomyopathy.