TNF-alpha and IL-1beta separately and synergistically depress human myocardial function. Sphingosine likely participates in the TNF-alpha and IL-1beta signal leading to human myocardial functional depression. Therapeutic strategies to reduce production or signaling of either TNF-alpha or IL-1beta may limit myocardial dysfunction in sepsis.

Senescent human myocardium exhibits decreased myocardial SERCA2a content with age, which may, in part, explain impaired myocardial function after either I/R or Ca2+ exposure.

No abstract

This study tested the hypothesis that in vivo norepinephrine (NE) treatment induces bimodal cardiac functional protection against ischemia and examined the roles of α1-adrenoceptors, protein kinase C (PKC), and cardiac gene expression in cardiac protection. Rats were treated with NE (25 μg/kg iv). Cardiac functional resistance to ischemia-reperfusion (25/40 min) injury was examined 30 min and 1, 4, and 24 h after NE treatment with the Langendorff technique, and effects of α1-adrenoceptor antagonism and PKC inhibition on the protection were determined. Northern analysis was performed to examine cardiac expression of mRNAs encoding α-actin and myosin heavy chain (MHC) isoforms. Immunofluorescent staining was performed to localize PKC-βI in the ventricular myocardium. NE treatment improved postischemic functional recovery at 30 min, 4 h, and 24 h but not at 1 h. Pretreatment with prazosin or chelerythrine abolished both the early adaptive response at 30 min and the delayed adaptive response at 24 h. NE treatment induced intranuclear translocation of PKC-βI in cardiac myocytes at 10 min and increased skeletal α-actin and β-MHC mRNAs in the myocardium at 4–24 h. These results demonstrate that in vivo NE treatment induces bimodal myocardial functional adaptation to ischemia in a rat model. α1-Adrenoceptors and PKC appear to be involved in signal transduction for inducing both the early and delayed adaptive responses. The delayed adaptive response is associated with the expression of cardiac genes encoding fetal contractile proteins, and PKC-βI may transduce the signal for reprogramming of cardiac gene expression.

No abstract