Lerman R H, Apstein C S, Kagan H M, Osmers E L, Chichester C O, Vogel W M, Connelly C M, Steffee W P
Circ Res. 1983 Sep;53(3):378-88. 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 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.
急性心肌梗死后的愈合情况可能决定心肌梗死后破裂和室壁瘤的发生率。因此，我们对36只家兔在冠状动脉结扎后1至8天进行了研究，并设置了18只假手术组作为对照，测量梗死左心室的胶原形成以及其对拉伸和破裂的机械抵抗力。脯氨酰羟化酶是胶原合成的一种细胞内酶，在心肌梗死后48小时，其活性从对照的3970±431计数/分钟每毫克可提取蛋白（cpm/mg）增加到9224±643 cpm/mg（P<0.01），并在心肌梗死后3天接近最大值（14518±2030 cpm/mg，P<0.01）。赖氨酰氧化酶是一种细胞外胶原交联酶，在72小时时其活性从对照的29.6±4.8增加到74.7±18.8 cpm/mg可提取蛋白（P<0.01），并在心肌梗死后4 - 6天达到峰值121.5±7.3（P<0.01）。羟脯氨酸作为胶原含量的指标，在72小时时从对照的2.8±0.2增加到5.3±0.6毫克/克干重（P<0.05），并在心肌梗死后8天继续增加（14.5±1.7毫克/克干重；P<0.01）。当酶活性和羟脯氨酸含量相对于其他参考基准（包括DNA、组织蛋白、干重和整个左心室）表示时，得到了类似的结果。梗死左心室的力学性能通过向离体左心室内充气球直至破裂来测定。正常左心室的破裂阈值为[664±43毫米汞柱（n = 16）]，与心肌梗死后1 - 8天梗死左心室的破裂阈值无显著差异。然而，心肌梗死后1 - 4天，左心室破裂更常发生在心肌梗死部位（59%），而在胶原含量显著增加的6天和8天，破裂发生率为18%（P = 0.03）。假手术组和正常组左心室破裂点的壁应力为30±2克/平方毫米；离体左心室肌条的抗张强度为25±4克/平方毫米，心肌梗死后7天离体瘢痕条的抗张强度为59±7克/平方毫米。梗死左心室的被动硬度在心肌梗死后4天从对照的61±5增加到94±6毫米汞柱/100微升（P<0.05），在6天增加到100±7毫米汞柱/100微升（P<0.01）。在心肌梗死后的8天内，硬度与羟脯氨酸含量相关（r = 0.599；P<0.001）。因此，在心肌梗死后最初的48小时内，即在胶原含量增加之前，急性梗死的心室对破裂具有高度抵抗力。这一结果表明梗死前的胶原含量在预防破裂方面具有重要作用。心肌梗死后72小时后，胶原合成似乎是梗死硬度以及梗死心室对破裂抵抗力的一个决定因素。
