[Activation of cardiac caspases: a double-edged weapon implicated in cardiac dysfunction]. / L'activation des caspases dans les cellules cardiaques: une arme a double tranchant impliquée dans la dysfonction cardiaque.

Low dead cell levels detected in various cardiac pathologies led to consider cardiac apoptosis as epiphenomena without repercussion on heart function. However, apoptosis prevention, and more specifically caspase inhibition, has been associated with major myocardial contractile performance improvement. This review describes specifically caspase involvement in myocardial dysfunction and highlights typical cardiomyocyte apoptosis signaling features. Thus caspase neutralization may represent a promising therapeutic strategy in heart disease treatments.

Cytokine profile of human septic shock serum inducing cardiomyocyte contractile dysfunction.

This study was designed to measure nitrite/nitrate and cytokine levels of serum obtained from septic shock patients and to describe potential depressant effects of human septic serum on rat cardiomyocytes. Serum was prepared from 10 non-septic patients and 10 patients with documented septic shock. Adult rat ventricular myocytes were exposed to 20 % serum in the medium. Cardiomyocyte contractility was assessed by measuring shortening fraction and shortening velocity. Serum levels of nitrite/nitrate, a marker of nitric oxide final metabolites, and cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL) 1beta, 6, 10, 8 and 12p70) were measured. Compared with serum from non-septic patients, serum of septic shock patients induced rapid reduction of the extent and velocity of shortening in isolated cardiomyocytes. Nitrite/nitrate, TNF-alpha, IL-1beta and IL-12p70 concentrations of tested serum for cardiomyocyte studies were not increased in septic serum compared with controls. In contrast, septic serum that induced a depression of in vitro contractility, had increased levels of IL-6, IL-8 and IL-10. We can conclude that the depression of in vitro contractility induced by septic serum is not directly dependent on elevated levels of nitric oxide metabolites, TNF-alpha or IL-1beta. Our results support the view that other cytokines, including IL-6, IL-8 and IL-10, are potent circulating mediators of myocardial depression in cardiomyocytes.