[Experimental study on elucidating pathogenesis of adriamycin induced cardiomyopathy (author's transl)].
For the determination of the pathophysiological mechanisms responsible for the adriamycin-induced cardiomyopathy we investigated the acute myocardial effects of this drug on contractile behavior in cultured embryonic ventricular cells in comparison to metabolic inhibitors, e.g., 2,4-dinitrophenol. There could be demonstrated a fall in contraction amplitude due to exposure to adriamycin, an increase in heart rate and the occurrence of "after-contractions". The fall in contraction could be explained by a decreased Ca-uptake by the sarcoplasmic reticulum (SR) and/or the mitochondria, leading to a rise in [Ca2+]i. This would tend to reduce spontaneous rate in pacemaker cells, to increase gK (conductance of potassium) and to influence the conduction. 10 microgram/ml adriamycin showed a 25% increment of K-flux above rest. A similar result was obtained by use of 10(-4) mmol/l 2,4-DNP which also caused cessation of spontaneous activity. This increment in K-flux, a parameter for K-permeability, might be caused by an increase in [Ca2+]i. The possible origin of this increment of [Ca2+]i might be of mitochondrial nature.l Thus an acute perturbance of mitochondrial function might give rise to [Ca2+]i, since mitochondria are known as Ca-buffering compartment. The pathophysiological mechanisms of the adriamycin cardiomyopathy therefore can be seen in the increase of [Ca2+]i.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000503:physiopathology; D002642:Chick Embryo; D004317:Doxorubicin / Q000009:adverse effects*; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism
D000963:Antimetabolites; D004317:Doxorubicin; D011188:Potassium; D002118:Calcium
Experimentelle Untersuchungen zur Klärung der Pathogenese der durch Adriamycin induzierten Kardiomyopathie.