TTC is accompanied by severe morphological alterations potentially resulting from catecholamine excess followed by microcirculatory dysfunction and direct cardiotoxicity. However, the affected myocardium represents a high potential of structural reconstitution which correlates with the rapid functional recovery.

BACKGROUND Although recent investigations report the elevation of plasma endothelin (ET) in congestive heart failure (CHF), it remains unclear if this elevation is that of the biologically active peptide ET-1 or of its precursor big-ET. Furthermore, it is unclear if such elevation is associated with increased myocardial ET and if the molecular form from cardiac tissue is altered ET. Last, it remains to be established whether circulating ET is increased at the earliest stage of CHF in patients with asymptomatic left ventricular dysfunction and correlates with the magnitude of ventricular dysfunction. METHODS AND RESULTS The present study was designed to investigate concentrations and molecular forms of ET in plasma and cardiac tissue in healthy subjects and CHF patients with New York Heart Association (NYHA) class I through IV using cardiac radionuclide angiogram, cardiac myocardial biopsy, radioimmunoassay, gel permeation chromatography (GPC), and immunohistochemical staining (IHCS). Plasma ET was increased only in patients with moderate (NYHA class III) or severe (NYHA class IV) CHF compared with healthy subjects and individuals with asymptomatic (NYHA class I) or mild (NYHA class II) CHF. The elevation of circulating ET in CHF showed a negative correlation with left ventricular ejection fraction and cardiac index and a positive correlation with functional class and left ventricular end-diastolic volume index. GPC demonstrated that immunoreactive plasma ET was ET-1 in healthy subjects and both mature ET-1 and its precursor big-ET in severe CHF patients, with big-ET the predominant molecular form. Cardiac tissue concentrations and IHCS revealed ET presence in healthy atrial and ventricular tissue, which were not different in severe CHF. GPC revealed that the molecular form of cardiac ET was ET-1 in both healthy and CHF hearts. CONCLUSIONS The present study establishes for the first time that the elevation of plasma ET in severe human CHF represents principally elevation of big-ET. Second, ET is present in healthy and failing myocardia, and its activity by both immunohistochemistry and radioimmunoassay is not changed in CHF. Furthermore, the elevated plasma ET is characteristic of severe CHF and not asymptomatic or mild CHF. In addition, the degree of plasma elevation of ET correlates with the magnitude of alterations in cardiac hemodynamics and functional class. The present study confirms and extends previous investigations of ET in human CHF and establishes the evolution of circulating and local cardiac ET in the spectrum of human CHF.

NT-proBNP is elevated in patients with aortic valve disease linked to disease severity and decreases after successful surgical therapy but increases in conservatively treated patients. These data underline the consistent relation of NT-proBNP to severity of aortic valve disease. Therefore, NT-proBNP should be considered as a biomarker for the monitoring of disease during follow-up, but further studies are warranted.

No abstract

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ETA and ETB receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg-1.min-1) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 micrograms.kg-1.min-1), a selective ETA antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ETB receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ETA receptor contributes to the renal vasoconstriction, whereas the ETB receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ETA or ETB receptor activation.

No abstract

The current study was undertaken to investigate the presence of CNP immunoreactivity in both human kidney and urine. Immunohistochemical staining with an indirect immunoperoxidase method utilizing an antibody which is 100% cross-reactive to both CNP-53 and CNP-22 was performed on five human kidney specimens (three biopsies of normal cadaveric donor kidneys and two of normal autopsy specimens). CNP immunoreactivity was positive in proximal, distal and medullary collecting duct tubular cells in a cytoplasmic and granular staining pattern. CNP immunoreactivity was also determined in the urine of five healthy volunteers utilizing a sensitive and specific double-antibody radioimmunoassay with a mean concentration of 10.8 +/- 1.0 pg/ml. With the utilization of high pressure liquid chromatography, this immunoreactivity proved to be consistent with both the low molecular weight form, CNP-22, as well as the high molecular weight form, CNP-53. Urinary excretion of CNP was also measured in normal subjects (N = 5) and in patients with congestive heart failure (CHF, N = 6). CHF patients excreted over three times more CNP than normals (27.2 +/- 2.8 vs. 8.7 +/- 0.81 pg/min, P < 0.004) despite no difference between the two groups in plasma CNP concentrations (6.97 +/- 0.28 vs. 8.08 +/- 1.52 pg/ml, P = NS). This study demonstrates for the first time the presence of CNP immunoreactivity in human kidney and suggests that renal tubular cells may be an additional non-vascular site of synthesis for this cardiorenal acting peptide. This study also demonstrates an increase in urinary CNP excretion in congestive heart failure.

Atrial natriuretic peptide hormone of cardiac origin, which is released in response to atrial distension and serves to maintain sodium homeostasis and inhibit activation of the renin-angiotensin-aldosterone system. Congestive heart failure is a clinical syndrome characterized by increased cardiac volume and pressure overload with an inability to excrete a sodium load, which is associated with increased activity of systemic neurohumoral and local autocrine and paracrine mechanisms. Circulating atrial natriuretic peptide is greatly increased in congestive heart failure as a result of increased synthesis and release of this hormone. Atrial natriuretic peptide has emerged as an important diagnostic and prognostic serum marker in congestive heart failure. In early heart failure, it may play a key role in preserving the compensated state of asymptomatic left ventricular dysfunction. Despite increased circulating atrial natriuretic peptide in heart failure, the kidney retains sodium and is hyporesponsive to exogenous and endogenous atrial natriuretic peptide. The mechanism for the attenuated renal response is multifactorial and includes renal hypoperfusion, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. Therapeutic strategies to potentiate the biologic actions of atrial natriuretic peptide may prolong the asymptomatic phase and delay progression to overt congestive heart failure.