title: Constitutive cardiac overexpression of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase delays myocardial failure after myocardial infarction in rats at a cost of increased acute arrhythmias.
abstract: BACKGROUND
  Heart failure often complicates myocardial infarction (MI), and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a) is underexpressed in the failing myocardium. We examined the effect of preexisting cardiac SERCA2a protein overexpression on rat survival and left ventricular (LV) remodeling after MI.
  
  
  RESULTS
  Baseline myocardial SERCA2a expression was 37% higher in transgenic (TG) rats than in their wild-type (WT) controls, consistent with enhanced myocardial function. The mortality rate of TG rats during the 24 hours after surgical MI was higher than that of WT rats (71% versus 35%, P<0.001), associated with a higher frequency of ventricular arrhythmias, and was normalized by lidocaine treatment. The increased acute-phase mortality in TG rats was not accompanied by increased 6-month mortality. Function of the noninfarcted myocardium, as assessed by tissue Doppler imaging, was higher in TG rats than in WT rats for up to 1 month after MI, a beneficial effect no longer observed at 3 months. LV remodeling and global function were similar in TG and WT rats. No difference in papillary muscle function was found at 6 months.
  
  
  CONCLUSIONS
  Constitutive cardiac SERCA2a overexpression has a transient beneficial effect on remote myocardium function in rat MI, with no improvement in LV global function or prevention of LV remodeling and failure. This benefit is associated with a higher risk of acute mortality, which is prevented by lidocaine treatment.
authors.affiliation: INSERM U460, Xavier Bichat Medical School, University of Paris 7, France.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Escoubet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Prunier
authors.forename: Julien
authors.initials: J
authors.lastname: Amour
authors.forename: Warner S
authors.initials: WS
authors.lastname: Simonides
authors.forename: Benoît
authors.initials: B
authors.lastname: Vivien
authors.forename: Christophe
authors.initials: C
authors.lastname: Lenoir
authors.forename: Michèle
authors.initials: M
authors.lastname: Heimburger
authors.forename: Christine
authors.initials: C
authors.lastname: Choqueux
authors.forename: Barnabas
authors.initials: B
authors.lastname: Gellen
authors.forename: Bruno
authors.initials: B
authors.lastname: Riou
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Franz
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mercadier
mesh_terms: D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D001145:Arrhythmias, Cardiac / Q000453:epidemiology / Q000209:etiology*; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D002303:Cardiac Output, Low / Q000209:etiology*; D007700:Kinetics; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D016019:Survival Analysis; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases