Reversibility and pathohistological basis of left ventricular remodeling in hibernating myocardium.
The phenomenon of left ventricular (LV) remodeling with dilatation, wall thinning, and increased muscle mass has previously been reported in pigs with 7-day myocardial hibernation. This study investigated cellular and extracellular basis and reversibility of the structural LV remodeling with hibernating myocardium. Five groups of pigs were included: Group A: 7-day myocardial hibernation with a fixed coronary stenosis; Group B: 7-day hibernation with subsequent 3-week reperfusion by release of the stenosis; Group C: control group with sham operation; Group D: 24-hour myocardial hibernation to define structural mechanism of initial wall thinning in the hibernating region without confounding factors of cell loss or hypertrophy, Group E: 4-week myocardial hibernation to exclude the possibility of spontaneous regression of LV remodeling with hibernation. LAD flow decreased by 38+/-12% (p<0.01) with a significant decrease in systolic wall thickening at 7 days of hibernation with severe coronary stenosis (Group A). End-diastolic wall thickness decreased by 19% (p<0.01) accompanied by a decrease in myocyte number across the wall (44%) and in myocyte density (24%), a significant increase in myocyte width (17%), a mild increase in interstitial tissues in hibernating region, and significant increases in LV diastolic volume and in LV mass at 7 days. After reperfusion (Group B), LV volume decreased, LV ejection fraction improved, and myocyte hypertrophy regressed with a decreased LV mass index without a significant change in interstitial tissue. LV remodeling progressed with further increases in LV volume, mass, and interstitial fibrosis in 4-week hibernation. In pigs undergoing 24 hours of myocardial hibernation (Group D), end-diastolic LV wall thickness decreased significantly in the hibernating region with a proportional decrease in the transmural myocyte number but without changes in myocyte width, myocyte density, or interstitial tissues. Therefore, progressive gross LV remodeling associated with hibernating myocardium is accompanied by increasing myocyte hypertrophy and interstitial fibrosis. In hibernating myocardial region, wall thinning is proportional to a decreased myocyte number across the LV wall, indicating slippage of myocytes as a preponderant mechanism for the wall thinning. Myocyte hypertrophy develops within 7 days in hibernating myocardium, causing an increase in LV mass. These changes are partially reversible after reperfusion.
Lai
T
T
Division of Cardiology, Hartford Hospital, University of Connecticut School of Medicine, Hartford, CT, USA.
Fallon
J T
JT
Liu
J
J
Mangion
J
J
Gillam
L
L
Waters
D
D
Chen
C
C
D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000209:etiology / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics; D009200:Myocardial Contraction / Q000502:physiology; D017682:Myocardial Stunning / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013552:Swine; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling