Coronary artery disease progression is associated with increased resistance of hearts and myocytes to cardiac insults.
OBJECTIVE
To investigate whether coronary artery disease alters vulnerability of hearts and myocytes to cardiac insults. To address this issue, we developed an experimental model of coronary artery disease.


METHODS
Prospective, experimental study.


METHODS
University experimental research laboratories.


METHODS
Apolipoprotein E knockout mice.


METHODS
Male apolipoprotein E knockout mice, aged 8 wks, were fed either a normal or high-fat diet.


RESULTS
High-fat feeding for 24 wks induced atherosclerosis in the coronary arteries, was associated with myocardial infarction, and produced evidence of myocardial metabolic anaerobic stress when compared with apolipoprotein E knockout mice fed normal diet. Myocytes and hearts from both groups had similar morphometric and hemodynamic characteristics. During global ischemia, hearts with coronary disease had shorter time to enter into rigor and developed greater ischemic contracture. They were markedly more resistant to reperfusion injury than nondiseased hearts, as shown by cardiac function, release of cardiac enzymes, and metabolic preservation. An increase in prosurvival signaling was detected in diseased hearts, as shown by a higher ratio of phospho-Akt/total Akt than in nondiseased hearts. Myocytes from diseased heart exposed to metabolic inhibition and reperfusion had fewer arrhythmias than myocytes from nondiseased heart. These differences are not due to high-fat feeding, as hearts of wild-type mice fed this diet were more, not less, vulnerable to cardiac insults.


CONCLUSIONS
This work suggests that chronic partial ischemia associated with progression of coronary artery disease preconditions myocytes and hearts against subsequent acute cardiac insults.
Chase
Anabelle
A
Faculty of Medicine and Dentistry, Bristol Heart Institute, University of Bristol, Bristol, UK.
Jackson
Christopher L
CL
Angelini
Gianni L
GL
Suleiman
M-Saadeh
MS
D000818:Animals; D003324:Coronary Artery Disease / Q000150:complications*; D004041:Dietary Fats / Q000009:adverse effects*; D018450:Disease Progression; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032342:Muscle Cells / Q000502:physiology*; D017202:Myocardial Ischemia / Q000209:etiology; D015428:Myocardial Reperfusion Injury / Q000150:complications*
D004041:Dietary Fats