Congestive heart failure: pathophysiologic consequences of neurohormonal activation and the potential for recovery: part II.

The congestive heart failure syndrome has its pathophysiologic origins rooted in neurohormonal activation, including hormone-mediated salt and water retention with ensuing central and systemic venous congestion. A systemic illness involving soft tissues and bone compounds this syndrome. Despite its complexity, however, many of these pathophysiologic consequences may prove reversible. Several lines of evidence, including responses to bed rest, pharmaceuticals and circulatory assist devices, suggest the potential for recovery exists and includes both the heart and systemic tissues. The fundamental basis on which the potential for recovery resides relates to withdrawal of responses and stimuli to activation of the renin-angiotensin-aldosterone and adrenergic nervous systems. Thus, a note of optimism would suggest congestive heart failure should no longer be considered an irreversible disorder. Instead, the potential for recovery must be considered as a reasonable expectation.

Congestive heart failure: pathophysiologic consequences of neurohormonal activation and the potential for recovery: part I.

What begins with a failing heart, unable to sustain adequate renal perfusion and metabolic needs of the tissues it serves becomes a systemic illness whose origins are rooted in neurohormonal activation. This unwanted homeostatic stressor response, an adaptation gone awry, has pathologic consequences. It involves endocrine properties of effector hormones arising from the adrenergic and renin-angiotensin-aldosterone systems. The clinical syndrome congestive heart failure (CHF) has its symptoms and signs rooted in a hormonally mediated salt-avid state. The ensuing salt and water retention includes the expansion of the intravascular space with consequent central and systemic venous congestion that, respectively, involves the heart and lungs, the liver, gut and kidneys and ultimately the extravascular space. Other pathophysiologic outcomes contribute to a proinflammatory CHF phenotype. These include an ongoing adverse remodeling of the failing heart with lost necrotic cardiomyocytes and a consequent replacement fibrosis; wasting of soft tissues and resorption of bone; dyshomeostasis of extra- and intracellular mono- and divalent cations that contributes to the appearance of oxidative stress coupled with compromised antioxidant defenses and an immunostimulatory state with activated lymphocytes and monocytes elaborating proinflammatory cytokines. In this 2-part review, the pathophysiologic consequences associated with neurohormonal activation in CHF will first be reviewed. Next, several lines of evidence are considered that raise the hitherto unfathomable prospect for recovery from CHF, including reverse remodeling of the heart and systemic tissues.

A dyshomeostasis of electrolytes and trace elements in acute stressor states: impact on the heart.

Acute stressor states are associated with a homeostatic activation of the hypothalamic-pituitary-adrenal axis. A hyperadrenergic state follows and leads to a dyshomeostasis of several intra- and extracellular cations, including K, Mg, and Ca. Prolongation of myocardial repolarization and corrected QT interval (QTc) of the ECG are useful biomarkers of hypokalemia and/or hypomagnesemia and should be monitored to address the adequacy of cation replacement. A dyshomeostasis of several trace elements, including Zn and Se, are also found in critically-ill patients to compromise metalloenzyme-based antioxidant defenses. Collectively, dyshomeostasis of these electrolytes and trace elements have deleterious consequences on the myocardium: atrial and ventricular arrhythmias; induction of oxidative stress with reduced antioxidant defenses; and adverse myocardial remodeling, including cardiomyocytes lost to necrosis and replaced by fibrous tissue. To minimize such consequences during hyperadrenergic states, systematic surveillance of electrolytes and trace elements, together with QTc, are warranted. Plasma K and Mg should be maintained at > or =4.0 mEq/L and > or =2.0 mg/dL, respectively (the 4 and 2 rule).

Expression of a novel tropomyosin isoform in axolotl heart and skeletal muscle.

TPM1kappa is an alternatively spliced isoform of the TPM1 gene whose specific role in cardiac development and disease is yet to be elucidated. Although mRNA studies have shown TPM1kappa expression in axolotl heart and skeletal muscle, it has not been quantified. Also the presence of TPM1kappa protein in axolotl heart and skeletal muscle has not been demonstrated. In this study, we quantified TPM1kappa mRNA expression in axolotl heart and skeletal muscle. Using a newly developed TPM1kappa specific antibody, we demonstrated the expression and incorporation of TPM1kappa protein in myofibrils of axolotl heart and skeletal muscle. The results support the potential role of TPM1kappa in myofibrillogenesis and sarcomeric function.