Elucidating 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. Experimental work with neonatal and adult cardiomyocytes considerably contributed to this progress, facilitating the documentation of direct attenuation of the contractions of the heart muscle cell by toxins and mediators, as well as investigating the underlying cellular mechanisms. With this respect, contractile-depressant effects have been found in cardiomyocytes for many toxins and sepsis mediators, with endotoxin, Pseudomonas exotoxin A, tumor necrosis factor alpha, interleukin-1 and nitric oxide being the most relevant ones identified. 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.
Werdan
K
K
Department of Cardiac Intensive Care Medicine, Martin-Luther-University of Halle-Wittenberg, Halle/Saale, Germany.
Müller-Werdan
U
U
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000503:physiopathology*; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology; D005098:Exotoxins / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D018805:Sepsis / Q000503:physiopathology*; D013999:Timolol / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D002118:Calcium; D003907:Dexamethasone; D005098:Exotoxins; D009638:Norepinephrine; D010716:Phosphatidylinositols; D013999:Timolol; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A