Myocardial Healing and Repair after Experimental Infarction in the Rabbit

• Published in: Circulation research 1983-09, Vol.53 (3), p.378-388
• Main Authors: Lerman, Robert H, Apstein, Carl S, Kagan, Herbert M, Osmers, Ellen L, Chichester, Clinton O, Vogel, W Mark, Connelly, Carolyn M, Steffee, William P
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Collagen - biosynthesis; Coronary heart disease; Coronary Vessels - physiology; Heart; Hydroxyproline - metabolism; Ligation; Male; Medical sciences; Myocardial Infarction - physiopathology; Procollagen-Proline Dioxygenase - metabolism; Protein-Lysine 6-Oxidase - metabolism; Rabbits; Tensile Strength
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.53.3.378

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 μg (cpm/mg) extractable protein (P < 0.01) at 48 hours and was nearly maximal at 3 days postmyocardial infarction (14,518 ± 2,030 cpm/mg, P < 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 < 0.01) at 72 hours and peaked at 121.5 ± 7.3 (P < 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 μg/g dry weight (P < 0.05) at 72 hours and continued to increase at 8 days postmyocardial infarction (14.5 ±1.7 μg/g dry weight; P < 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/mm; tensile strength in isolated left ventricle muscle strips was 25 ± 4 g/mm and in isolated scar strips at 7 days postmyocardial infarction was 59 ± 7 g/mm. The passive stiffness of the infarcted left ventricle increased from control of 61 ± 5 to 94 ± 6 mm Hg/100 μ(P < 0.05) at 4 days and 100 ± 7 mm Hg/100 pi (P < 0.01) at 6 days postmyocardial infarction. Stiffness correlated with hydroxyproline content over the 8 days postmyocardial infarction (r = 0.599; P < 0.001). Thus, the acutely infarcted ventricle was highly resistant to