Molecular and cellular biochemistry
-
Mol. Cell. Biochem. · Oct 1996
ReviewElucidating molecular mechanisms of septic cardiomyopathy--the cardiomyocyte model.
In the multiple organ dysfunction syndrome of sepsis and septic shock the heart is one of the organs subject to failure. Many new insights into the mechanisms underlying septic cardiomyopathy were gained in the last years. ⋯ These substances interfere at clinically relevant concentrations with several main inotropic axes, not only with the beta-adrenoceptor/adenylyl cyclase and with the NO-cGMP-system-on which most of the interest is focused at present-but also with the alpha 1-adrenoceptor/phosphoinositide pathway and the Ca2+ homeostasis of the cardiomyocyte, the latter representing the common final inotropic pathway. Not a single cardiodepressant factor, but more likely a total bunch of toxins and mediators with different attack mechanisms seem to contribute to the picture of septic cardiomyopathy.
-
Mol. Cell. Biochem. · Oct 1996
Alterations in inotropy, nitric oxide and cyclic GMP synthesis, protein phosphorylation and ADP-ribosylation in the endotoxin-treated rat myocardium and cardiomyocytes.
To evaluate the effects of the in vivo endotoxin treatment of the rat on (1) the contractile responses in the subsequently isolated papillary muscle to adrenergic and cholinergic agonists and (2) the biochemical parameters (cyclic GMP, nitric oxide synthesis, protein phosphorylation and ADP-ribosyslation) in the subsequently isolated cardiomyocytes. Following the in vivo endotoxin treatment (4 mg/kg i.p., 18 h), contractile responses to increasing amounts of isoprenaline or to increasing amounts of oxotremorine in the presence of a fixed amount of isoprenaline were determined in isolated papillary strips. Activities of nitric oxide synthase, guanylyl cyclase, as well as phosphorylation of phospholamban and troponin-inhibitory subunit, and pertussis toxin-catalyzed and endogenous ADP-ribosylations were determined in the intact cardiomyocytes and subcellular fractions. ⋯ The activities of both nitric oxide synthase, primarily of the inducible form of the enzyme, and cytosolic guanylyl cyclase were higher while the phosphorylations of both phospholamban and troponin-inhibitory subunit were of lesser magnitude in the cardiomyocytes following the in vivo endotoxin treatment. Pertussis toxin-catalyzed ADP-ribosylation of the 41 kDa polypeptide, which is the alpha subunit of Gi, was also decreased. The results of the present study support the postulate that alterations in both the cyclic AMP and cyclic GMP signalling cascade contribute to the myocardial dysfunction caused by endotoxin and cytokines.