Delayed reperfusion has a beneficial effect on prognosis, independent of
infarct size. One potential mechanism to explain this observation may be an effect on
infarct healing. In this study, the impact of delayed reperfusion on two aspects of the healing process was examined, the activity of
matrix metalloproteinase (
MMP)
enzymes and the expression of
fibronectin (FN)
mRNA. The rat model of coronary artery
ligation was used and rats were randomly assigned to delayed reperfusion (150 min following coronary
ligation) or permanent
ligation. Animals were subsequently killed 1, 2, 3 and 7 days following
infarction.
Infarct tissue was harvested for
MMP activity (zymography), FN
mRNA (
RNase protection analysis) and
protein (immunofluorescence microscopy and Western analysis), and
collagen content (
hydroxyproline concentration).
Infarction produced marked activation of MMP-1, -2, and -9. Reperfusion significantly attenuated the activity of these
enzymes (approximately 50% reduction in
MMP-1, P=0.03 and ;60% reduction in
MMP-2 at 7 days, P=0.001; approximately 55% reduction in
MMP-9 at 24 h and 84% reduction at 48 h, P=0.01 and 0.002, respectively). Delayed reperfusion also produced a trend toward a greater increase in FN
mRNA 24 h following
infarction and immunofluorescent staining suggested the presence of more FN
protein at this point. These data demonstrate that delayed reperfusion alters
matrix metalloproteinase activity and
fibronectin mRNA expression in the
infarct zone. The impact of these changes on
infarct healing and their association with the improved prognosis of a patent
infarct vessel following
infarction will require further study.