Preconditioning protects the severely atherosclerotic mouse heart.
BACKGROUND
Coronary atherosclerosis has profound effects on vascular and myocardial biology, and it has been speculated that the atherosclerotic heart does not benefit from ischemic preconditioning.


METHODS
To investigate if atherosclerosis would influence the preconditioning response, Apolipoprotein E/low density lipoprotein (LDL) receptor double knockout mice (ApoE/LDLr-/-) were fed an atherogenic diet (21% fat, 0.15% cholesterol) for 6 to 8 months. At that time, extensive atherosclerotic lesions throughout the coronary tree were seen in transverse sections stained with Oil Red-O. Hearts of ApoE/LDLr-/- mice were Langendorff-perfused with 40 minutes of global ischemia and 60 minutes reperfusion, and compared with C57BL/6 controls. Preconditioning with two episodes of 2 minutes of ischemia and 5 minutes reperfusion, or exposing the mice to a hyperoxic environment (O2 > 98%) for 60 minutes before heart perfusion, was performed.


RESULTS
Hearts of mice with coronary atherosclerosis had worse postischemic function, and increased infarct size and troponin T release compared to hearts of C57BL/6 mice. Ischemic preconditioning improved postischemic ventricular function, and reduced myocardial infarct size and troponin T release in both normal and ApoE/LDLr-/- mice. The effects were most pronounced in ApoE/LDLr-/- hearts. Exposure to hyperoxia exerted a similar protection of function and cell viability of ApoE/LDLr-/- mice hearts.


CONCLUSIONS
These findings suggest that the severely atherosclerotic heart may be protected by preconditioning induced by ischemia or hyperoxia.
Li
G
G
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Tokuno
S
S
Tähep ld
P
P
Vaage
J
J
Löwbeer
C
C
Valen
G
G
D000704:Analysis of Variance; D000818:Animals; D003324:Coronary Artery Disease / Q000473:pathology / Q000628:therapy*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D006334:Heart Function Tests; D018496:Hyperoxia; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D020107:Troponin T / Q000032:analysis
D020107:Troponin T