In an experimental rabbit model, the acutely infarcted ventricle was highly resistant to rupture during the initial 48 hours post-MI, after which collagen synthesis determined infarct stiffness.
Preinfarction collagen content prevents early post-MI rupture, while subsequent collagen synthesis determines infarct stiffness and resistance to rupture after 72 hours.
Adequacy of healing after acute myocardial infarction may determine the incidence of postmyocardial infarction rupture and ventricular aneurysm. Accordingly, in 36 rabbits, from 1 to 8 days after coronary ligation, and in 18 shams, we measured collagen formation and mechanical resistance of the infarcted left ventricle to stretch and rupture. Prolyl hydroxylase, an intracellular enzyme of collagen synthesis, increased from control activity of 3970 +/- 431 to 9224 +/- 643 counts/min per mg (cpm/mg) extractable protein (P less than 0.01) at 48 hours and was nearly maximal at 3 days postmyocardial infarction (14,518 +/- 2,030 cpm/mg, P less than 0.01). Lysyl oxidase, an extracellular collagen cross-linkage enzyme, increased from control activity of 29.6 +/- 4.8 to 74.7 +/- 18.8 cpm/mg extractable protein (P less than 0.01) at 72 hours and peaked at 121.5 +/- 7.3 (P less than 0.01) 4-6 days postmyocardial infarction. Hydroxyproline, a measure of collagen content, increased from control of 2.8 +/- 0.2 to 5.3 +/- 0.6 mg/g dry weight (P less than 0.05) at 72 hours and continued to increase at 8 days postmyocardial infarction (14.5 +/- 1.7 mg/g dry weight; P less than 0.01). When enzyme activities and hydroxyproline content were expressed relative to other reference bases, including DNA, tissue protein, dry weight, and total left ventricle, similar results were obtained. The mechanical properties of the infarcted left ventricle were determined by filling a balloon in the excised left ventricle until rupture. The rupture threshold in the normal left ventricle, 664 +/- 43 mm Hg (n = 16), was not significantly different from that of the infarcted left ventricle on days 1-8 postmyocardial infarction. However, left ventricular rupture occurred more often through the myocardial infarction on days 1-4 postmyocardial infarction (59%) than on days 6 and 8 (18%; P = 0.03) when collagen content had significantly increased. Wall stress at the point of rupture in left ventricles from shams and normals was 30 +/- 2 g/mm2; tensile strength in isolated left ventricle muscle strips was 25 +/- 4 g/mm2 and in isolated scar strips at 7 days postmyocardial infarction was 59 +/- 7 g/mm2. The passive stiffness of the infarcted left ventricle increased from control of 61 +/- 5 to 94 +/- 6 mm Hg/100 microliters (P less than 0.05) at 4 days and 100 +/- 7 mm Hg/100 microliters (P less than 0.01) at 6 days postmyocardial infarction. Stiffness correlated with hydroxyproline content over the 8 days postmyocardial infarction (r = 0.599; P less than 0.001). Thus, the acutely infarcted ventricle was highly resistant to rupture during the initial 48 hours postmyocardial infarction, before any increase in collagen occurred. This result suggests that the preinfarction collagen content has an important role in preventing rupture. After 72 hours postmyocardial infarction, collagen synthesis appeared to be a determinant of infarct stiffness and resistance of the infarcted ventricle to rupture.
Lerman et al. (Thu,) conducted a other in Acute myocardial infarction (n=54). Coronary ligation (experimental infarction) vs. Sham operation was evaluated on Collagen formation and mechanical resistance of the infarcted left ventricle to stretch and rupture. In an experimental rabbit model, the acutely infarcted ventricle was highly resistant to rupture during the initial 48 hours post-MI, after which collagen synthesis determined infarct stiffness.