Constitutive cardiac overexpression of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase delays myocardial failure after myocardial infarction in rats at a cost of increased acute arrhythmias.
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.
Chen
Ying
Y
INSERM U460, Xavier Bichat Medical School, University of Paris 7, France.
Escoubet
Brigitte
B
Prunier
Fabrice
F
Amour
Julien
J
Simonides
Warner S
WS
Vivien
Benoît
B
Lenoir
Christophe
C
Heimburger
Michèle
M
Choqueux
Christine
C
Gellen
Barnabas
B
Riou
Bruno
B
Michel
Jean-Baptiste
JB
Franz
Wolfgang M
WM
Mercadier
Jean-Jacques
JJ
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
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases