Restraining acute infarct expansion decreases collagenase activity in borderzone myocardium.
BACKGROUND
After acute myocardial infarction, regional myocardial wall strains and stresses change and a complex cellular and biochemical response is initiated to remodel the ventricle. This study tests the hypothesis that changes in regional ventricular wall strains affect regional collagen accumulation and collagenase activity.


METHODS
Fourteen sheep had acute anteroapical infarction that progressively expands into left ventricular aneurysm within 8 weeks. In 7 sheep, infarct expansion was restrained by prior placement of mesh over the area at risk. Fourteen days after infarction, and after hemodynamic and echocardiographic measurements, animals were euthanized for histology, measurements of hydroxyproline, matrix metalloproteinase-1 (MMP-1 or collagenase) and MMP-2 (gelatinase) activity, as well as collagen type I and III in infarcted, borderzone, and remote myocardium.


RESULTS
Restraining infarct expansion does not change collagen content or MMP-1 or MMP-2 activity in the infarct, but significantly increases the ratio of collagen I/III. In borderzone and remote myocardium infarct, restraint significantly increases collagen content and significantly reduces MMP-1 activity. MMP-2 activity is reduced (p = 0.059) in borderzone myocardium only. Between groups, the ratio of type I/III fibrillar collagen does not change in borderzone myocardium.


CONCLUSIONS
Fourteen days after acute myocardial infarction, restraining infarct expansion increases collagen accumulation in borderzone and remote myocardium, which may prevent expansion of hypocontractile, fully perfused "remodeling myocardium" adjacent to the infarct. This study demonstrates that changes in regional myocardial wall strain alter the cellular and biochemical processes involved in postinfarction ventricular remodeling.
Bowen
F W
FW
Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia, USA.
Jones
S C
SC
Narula
N
N
St John Sutton
M G
MG
Plappert
T
T
Edmunds
L H
LH
Dixon
I M
IM
D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology / Q000601:surgery; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D011126:Polypropylenes; D019736:Prostheses and Implants; D012756:Sheep; D013526:Surgical Mesh; D013536:Suture Techniques; D020257:Ventricular Remodeling / Q000502:physiology*
D024042:Collagen Type I; D024043:Collagen Type II; D011126:Polypropylenes; D017364:Collagenases; D018093:Gelatinases