Chronic effects of ethanol on cultured myocardial cells: ultrastructural and morphometric studies.
Ultrastructural alterations of the myocardium due to chronic ethanol exposure were investigated using an in vitro system-mouse ventricular myocardial cells in a monolayer culture, which were spontaneously and synchronously contracting-by chronic exposure to 12.5, 50, and 200 mM ethanol for up to 21 days. Morphometric analyses revealed that exposure to 12.5 mM ethanol for 14 days induced an increase in the number of residual bodies, which are lysosomes containing electron-dense, amorphous materials. Some cells exposed to 50 mM ethanol for 14 days contained an accumulation of glycogen granules, increasing in inverse proportion to the mitochondrial volume. The volumetric proportion of myofibrils on day 14 decreased as the ethanol dose became lower, and was in proportion to large and giant mitochondria within the limits of three ethanol groups. Dose-dependent increases in the size and volumetric proportion of mitochondria were observed after the 14-day exposure; at a low dose (12.5 mM) mitochondria of usual size tended to increase, whereas at a high dose (200 mM) giant mitochondria increased. Coincidentally with this mitochondrial increase or gigantism, all ethanol groups showed higher beat rates than the control. Consequently, it is most likely that chronic 14-day exposures to these three ethanol doses remodel the cellular function of the in vitro myocardium in different ways; the 200-mM dose induced mitochondrial hypertrophy, an adaptive response to switch myocardial energy metabolism over to some special one; the 50-mM dose was a boundary dose; and the 12.5-mM dose mostly mimicked the chronic in vivo administration of ethanol and induced slightly degenerative alterations-increased residual bodies and lysosomes, decreased myofibrils and lowered mitochondrial respiratory function.
Mashimo
Keiko
K
Department of Legal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8602 Tokyo, Japan. kei-mam@nms.ac.jp
Sato
Shigeru
S
Ohno
Youkichi
Y
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008854:Microscopy, Electron; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure
D000431:Ethanol