Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure.
Young mice tolerate myocardial loss after coronary artery ligation (CAL) without congestive heart failure (CHF) signs or mortality. We predicted a CHF phenotype after CAL in aged mice. Left coronary artery ligation produced permanent myocardial infarcts (MI). Mortality was higher in male 14-mo-old C57BL/6N mice (Older mice) than in 2-mo-old mice (Young mice) (16 of 25 Older mice died vs. 0 of 10 Young mice, P < 0.02). After 8 wk, rales, weight loss, and lethargy preceded deaths. Captopril (50 mg x kg(-1) x day(-1)) increased Older mouse survival (6 of 22 died, P < 0.02). Captopril improved systolic function (peak aortic blood velocity) from 76 +/- 6% of baseline in untreated Older mice to 93 +/- 8% (P < 0.036). At 24 h, MI comprised 28 +/- 4% of the left ventricle in Young mice, surprisingly larger than that in Older mice (18 +/- 2%, P < 0.011). Endocardial area underlying the infarct scar was significantly larger in Older mice than in Young mice. Captopril did not reduce expansion but markedly reduced septal hypertrophy. Aging reduces compensatory ability in mice despite smaller acute infarcts. Less effective myocardial repair, greater infarct expansion, and septal hypertrophy are seen with aging. Aging is a more relevant murine model of post-MI heart failure in patients.
Gould
Kenneth E
KE
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. gould@lilly.com
Taffet
George E
GE
Michael
Lloyd H
LH
Christie
Robert M
RM
Konkol
Debra L
DL
Pocius
Jennifer S
JS
Zachariah
Justin P
JP
Chaupin
Damian F
DF
Daniel
Sherita L
SL
Sandusky
George E
GE
Hartley
Craig J
CJ
Entman
Mark L
ML
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D002216:Captopril / Q000494:pharmacology; D006332:Cardiomegaly / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D003327:Coronary Disease / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D006346:Heart Septum / Q000473:pathology; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril