title: Ventricular myocyte caspases are directly responsible for endotoxin-induced cardiac dysfunction.
abstract: BACKGROUND
  Although most of the deleterious effects of sepsis-induced apoptosis have been attributed to increased lymphocyte cell death, caspase activation may directly alter cell function of different organ systems. We postulated that left ventricular (LV) cardiomyocyte caspase activation is directly involved in sepsis-induced heart contractile dysfunction.
  
  
  RESULTS
  LV cardiomyocytes isolated 4 hours after rat treatment with endotoxin injection (10 mg/kg) displayed major reductions in contractile reserve and myofilament response to Ca2+. Concomitantly, endotoxin also induced increases in LV cardiomyocyte caspase-3, -8, and -9-like activities, which were associated with sarcomeric structure destruction and cleavage of components of the cardiac myofilament. Interestingly, zVAD.fmk treatment of septic rat prevented LV cardiomyocyte contractile dysfunction, reductions in myofilament response to calcium, troponin T cleavage, and sarcomere destruction. Serum (10%) of endotoxin-treated rats induced contractile dysfunction, caspase-3-like activity increase, and troponin T cleavage of naive LV cardiomyocytes. The effects of septic serum were prevented in LV cardiomyocytes isolated from zVAD.fmk- or zDEVD.cmk-treated rats or LV cardiomyocytes preincubated with zVAD.fmk or zDEVD.cmk.
  
  
  CONCLUSIONS
  The results show an important relationship between endotoxin-induced caspase activation and reduced contractile reserve and sarcomere disarray at the level of single LV cardiomyocytes.
authors.affiliation: EA 2689, CHRU, and Université de Lille 2, IFR 114 IMPRT, Lille, France.
authors.forename: Steve
authors.initials: S
authors.lastname: Lancel
authors.forename: Olivier
authors.initials: O
authors.lastname: Joulin
authors.forename: Raphael
authors.initials: R
authors.lastname: Favory
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Goossens
authors.forename: Jérome
authors.initials: J
authors.lastname: Kluza
authors.forename: Claude
authors.initials: C
authors.lastname: Chopin
authors.forename: Pierre
authors.initials: P
authors.lastname: Formstecher
authors.forename: Philippe
authors.initials: P
authors.lastname: Marchetti
authors.forename: Remi
authors.initials: R
authors.lastname: Neviere
mesh_terms: D008841:Actin Cytoskeleton / Q000473:pathology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D004731:Endotoxins / Q000009:adverse effects*; D006331:Heart Diseases / Q000209:etiology* / Q000473:pathology; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000473:pathology; D018805:Sepsis / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D020107:Troponin T / Q000378:metabolism
chemical_list: D004731:Endotoxins; D020107:Troponin T; D020169:Caspases; D002118:Calcium