Development of contractile dysfunction in rat heart failure: hierarchy of cellular events.
The cellular mechanisms underlying the development of congestive heart failure (HF) are not well understood. Accordingly, we studied myocardial function in isolated right ventricular trabeculae from rats in which HF was induced by left ventricular myocardial infarction (MI). Both early-stage (12 wk post-MI; E-pMI) and late, end-stage HF (28 wk post-Mi; L-pMI) were studied. HF was associated with decreased sarcoplasmic reticulum Ca(2+) ATPase protein levels (28% E-pMI; 52% L-pMI). HF affected neither sodium/calcium exchange, ryanodine receptor, nor phospholamban protein levels. Twitch force at saturating extracellular [Ca(2+)] was depressed in HF (30% E-pMI; 38% L-pMI), concomitant with a marked increase in sensitivity of twitch force toward extracellular [Ca(2+)] (26% E-pMI; 68% L-pMI). Ca(2+)-saturated myofilament force development in skinned trabeculae was unchanged in E-pMI but significantly depressed in L-pMI (45%). Tension-dependent ATP hydrolysis rate was depressed in L-pMI (49%), but not in E-pMI. Our results suggest a hierarchy of cellular events during the development of HF, starting with altered calcium homeostasis during the early phase followed by myofilament dysfunction at end-stage HF.
Daniels
Marcel C G
MC
Department of Physiology and Biophysics MC901, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612, USA.
Naya
Taihei
T
Rundell
Veronica L M
VL
de Tombe
Pieter P
PP
D008841:Actin Cytoskeleton / Q000502:physiology; D000465:Algorithms; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002303:Cardiac Output, Low / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure; D014129:Trabecular Meshwork / Q000502:physiology
D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D018995:Myosin Heavy Chains