Reappearance of myocytes in ovine infarcts produced by six hours of complete ischemia followed by reperfusion.
BACKGROUND
In this study we tested the hypothesis that delayed reperfusion of ischemic myocardium-too late to save myocytes-attenuates infarct expansion and improves collagen synthesis.


METHODS
The hypothesis was tested in a sheep model of anteroapical infarction that has no collateral blood flow to the area at risk. After coronary ligation or arterial occlusion for 1 or 6 hours, sheep had serial hemodynamic and quantitative echocardiographic studies before and after infarction and 2, 5, 8, and 12 weeks later. Hearts were examined by light and electron microscopy at 2 and 12 weeks; hydroxyproline and ratios of type I/III collagen were measured at 12 weeks.


RESULTS
After coronary occlusion, left ventricular (LV) function progressively decreased and size increased to form an anteroapical aneurysm. After 1 hour of ischemia, neither resting LV size nor function changed; the infarct contained a midmyocardial scar between epicardial and endocardial muscle. After 6 hours of ischemia, LV function was significantly better than that in nonperfused sheep. Two weeks after 6 hours of ischemia, no viable myocytes were visible by light microscopy, but electron micrographs showed rare intact nucleated myocytes with scarce cytoplasmic myofibrils. At the 12th week epicardial and endocardial myocytes reappeared in the infarct. Infarct collagen type I/III ratios were 1.2 in reperfused groups and 0.7 in nonperfused sheep.


CONCLUSIONS
Delayed reperfusion causes loss and subsequent reappearance of ovine epicardial myocytes, improves collagen type I/III ratios, and attenuates LV dilatation and loss of function. One hypothesis to explain the reappearance of myocytes is that reperfusion partially reverses an incomplete apoptotic process.
Bowen
F W
FW
Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia, USA.
Hattori
T
T
Narula
N
N
Salgo
I S
IS
Plappert
T
T
Sutton
M G
MG
Edmunds
L H
LH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004699:Endocardium / Q000473:pathology; D005260:Female; D008297:Male; D008854:Microscopy, Electron; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D012756:Sheep
D003094:Collagen