Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation.

Our objective was to address the balance of inducible nitric oxide (NO) synthase (iNOS) and arginase and their contribution to contractile dysfunction in heart failure (HF). Excessive NO formation is thought to contribute to contractile dysfunction; in macrophages, increased iNOS expression is associated with increased arginase expression, which competes with iNOS for arginine. With substrate limitation, iNOS may become uncoupled and produce reactive oxygen species (ROS).

Presence of connexin 43 in subsarcolemmal, but not in interfibrillar cardiomyocyte mitochondria.

Cardiomyocytes contain subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria, which differ in their respiratory and calcium retention capacity. Connexin 43 (Cx43) is located at the inner membrane of SSM, and Cx43 is involved in the cardioprotection by ischemic preconditioning (IP). The function of Cx43-formed channels is regulated in part by phosphorylation at residues in the carboxy terminus of Cx43.

No impact of protein phosphatases on connexin 43 phosphorylation in ischemic preconditioning.

Cardiac connexin 43 (Cx43) is involved in infarct propagation, and the uncoupling of Cx43-formed channels reduces infarct size. Cx43-formed channels open upon Cx43 dephosphorylation, and ischemic preconditioning (IP) prevents the ischemia-induced Cx43 dephosphorylation. In addition to the sarcolemma, Cx43 is also present in the cardiomyocyte mitochondria.

Reduced calcium responsiveness characterizes contractile dysfunction following coronary microembolization.

Aims: We addressed calcium responsiveness in microembolized myocardium at 6 h after coronary microembolization (ME).

Methods And Results: In anesthetized pigs calcium responsiveness was determined as the increase of a myocardial work index (WI; LV pressure development vs. wall thickening) in response to a graded intracoronary infusion of CaCl(2) at baseline and at 6 h after ME or placebo, respectively.

Inhibition of the Na+/H+ exchanger attenuates the deterioration of ventricular function during pacing-induced heart failure in rabbits.

Aims: Inhibition of the Na+/H+-exchanger (NHE) preserves myocardial morphology and function in rat and mouse models of hypertrophy and failure. The mechanism(s) involved in such cardioprotective effects remain(s) unclear, but might involve blockade of increased protein kinase activity as observed in untreated hearts.

Methods And Results: We investigated the functional, morphological and biochemical consequences of NHE-inhibition with BIIB722 in rabbits with pacing-induced heart failure (HF).

Glucocorticoid treatment prevents progressive myocardial dysfunction resulting from experimental coronary microembolization.

Background: The frequency and importance of microembolization in patients with acute coronary syndromes and during coronary interventions have recently been appreciated. Experimental microembolization induces immediate ischemic dysfunction, which recovers within minutes. Subsequently, progressive contractile dysfunction develops over several hours and is not associated with reduced regional myocardial blood flow (perfusion-contraction mismatch) but rather with a local inflammatory reaction.

Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine.

Coronary microembolization results in progressive myocardial dysfunction, with causal involvement of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha uses a signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we induced coronary microembolization in anesthetized dogs and studied the role and sequence of NO, TNF-alpha, and sphingosine for the evolving contractile dysfunction.

Coronary microembolization: the role of TNF-alpha in contractile dysfunction.

Coronary microembolization is a frequent complication of atherosclerotic plaque rupture in acute coronary syndromes and during coronary interventions. Experimental coronary microembolization results in progressive contractile dysfunction associated with a local inflammation. We studied the causal role of tumor necrosis factor-alpha (TNF-alpha) in the progressive contractile dysfunction resulting from coronary microembolization.