Prevention of adverse electrical and mechanical remodeling with biventricular pacing in a rabbit model of myocardial infarction.

Background: Biventricular (BIV) pacing can improve cardiac function in heart failure (HF).

Objective: This study sought to investigate the mechanisms of benefit of BIV pacing using a rabbit model of myocardial infarction (MI).

Methods: New Zealand White rabbits were divided into 4 groups (sham-operated [C], MI with no pacing [MI], MI with right ventricular pacing [MI+RV], and MI with BIV pacing [MI+BIV]) and underwent serial electrocardiograms and echocardiograms.

Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-alpha.

Mice that overexpress the inflammatory cytokine tumor necrosis factor-alpha in the heart (TNF mice) develop heart failure characterized by atrial and ventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias, and increased mortality (males > females). Abnormalities in Ca2+ handling, prolonged action potential duration (APD), calcium alternans, and reentrant atrial and ventricular arrhythmias were previously observed with the use of optical mapping of perfused hearts from TNF mice. We therefore tested whether altered voltage-gated outward K+ and/or inward Ca2+ currents contribute to the altered action potential characteristics and the increased vulnerability to arrhythmias.

Atrial contractile dysfunction, fibrosis, and arrhythmias in a mouse model of cardiomyopathy secondary to cardiac-specific overexpression of tumor necrosis factor-{alpha}.

Transgenic mice overexpressing the inflammatory cytokine TNF-alpha in the heart develop a progressive heart failure syndrome characterized by biventricular dilatation, decreased ejection fraction, decreased survival compared with non-transgenic littermates, and earlier pathology in males. TNF-alpha mice (TNF1.6) develop atrial arrhythmias on ambulatory telemetry monitoring that worsen with age and are more severe in males.

Estrogen protects cardiac myogenic (H9c2) rat cells against lethal heat shock-induced cell injury: modulation of estrogen receptor alpha, glucocorticoid receptors, heat shock protein 70, and iNOS.

In the present study we have established that exposure of rat cardiac myoblasts (H9c2 cells) to 46 degrees C for 1 hour (lethal heat shock) resulted in optimal cell injury as determined by lactate dehydrogenase release. Pretreatment of H9c2 cells for 24 hours with 17beta-estradiol significantly protects myoblasts against subsequent lethal heat shock exposure in a concentration-dependent manner with maximum protection obtained at 1 microM of 17beta-estradiol. With Western blotting, it was observed that 17beta-estradiol-protected cells had significantly higher levels of the estrogen receptor alpha and inducible heat shock protein 70 (hsp70) as well as inducible nitric oxide synthase (iNOS) levels compared with lethal heat shock-exposed cells.

Transcription enhancer factor-1-related factor-transgenic mice develop cardiac conduction defects associated with altered connexin phosphorylation.

Background: Conduction system defects and slowed ventricular conduction are common in patients with systolic dysfunction and contribute to arrhythmias and sudden death. In animal models of heart failure, cardiac alpha1-adrenergic signaling is constitutively activated. Here, we report the effects of constitutive activation of alpha1-adrenergic signaling on connexin phosphorylation and cardiac conduction.

Transgenic overexpression of caveolin-3 in the heart induces a cardiomyopathic phenotype.

Caveolins are structural protein components of caveolar membrane domains. Caveolin-3, a muscle-specific member of the caveolin family, is expressed in skeletal muscle tissue and in the heart. The multiple roles that caveolin-3 plays in cellular physiology are becoming more apparent.

Evidence that NOS2 acts as a trigger and mediator of late preconditioning induced by acute systemic hypoxia.

Chronic systemic hypoxia (SH) enhances myocardial ischemic tolerance in mammals. We studied the delayed cardioprotection caused by acute SH and associated signaling mechanism. Conscious adult male mice were exposed to one or two cycles of hypoxia (H; 10% O(2)) or normoxia (21% O(2)) for various durations (30 min, 2 h, 4 h) followed by 24 h of reoxygenation.

Alpha-adrenergic receptor stimulation produces late preconditioning through inducible nitric oxide synthase in mouse heart.

Inducible nitric oxide synthase (iNOS) mediates late preconditioning (PC) induced by ischemia and pharmacological agents. Since alpha -adrenoceptor (alpha -AR) stimulation is one of the key triggers of PC, we hypothesized that activation of this receptor may induce delayed cardioprotective effect via iNOS-sensitive mechanisms. Adult male ICR mice were treated i.

Tamoxifen protects clonal mouse hippocampal (HT-22) cells against neurotoxins-induced cell death.

In the present work using an established clonal mouse hippocampal (HT-22) cell line, we have examined whether the estrogen antagonist tamoxifen antagonizes the observed neuroprotective effects of estrogen against glutamate and amyloid beta protein neurotoxicity. Results obtained suggest that like estrogen, tamoxifen protects HT-22 cells against both 5mM glutamate and 2 microM amyloid beta protein induced cell death in a concentration dependent manner. Optimum protection was obtained at 500 nM tamoxifen.