Rossi M A
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
J Hypertens. 1998 Jul;16(7):1031-41. doi: 10.1097/00004872-199816070-00018.
To investigate pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans.
Seventeen human hearts were studied. Group 1 consisted of control hearts (four hearts, weighing 280 +/- 40 g each), from subjects who had had no evidence of heart disease and for whom the diagnoses of death were noncardiac. Groups 2 (five hearts, weighing 440 +/- 50 g each), 3 (five hearts, weighing 560 +/- 50 g each), and 4 (three hearts, weighing 680 +/- 60 g each) consisted of hearts from subjects who had had a history of systemic hypertension. All hearts had no valvular deformities and no evidence of ischemic disease at the postmortem examination. A cell-maceration method was employed to evaluate the myocardial connective matrix after removal of the nonfibrous elements of myocardial tissue, leaving behind a noncollapsed matrix, thus allowing a better three-dimensional view. Myocardial tissue was also processed for conventional light microscopic and morphometric studies.
The minor transverse diameter of myocytes from hearts in groups 1-4 hearts were 13.7 +/- 7.8, 23.7 +/- 3.4, 26.6 +/- 3.7, and 32.8 +/- 5.8 microm, respectively. The volume fraction of fibrosis of the controls was 6.5%, whereas the volume fractions in hypertensive hearts increased progressively according to heart weight: 15.4, 22.9, and 31.1% for hearts in groups 2, 3, and 4, respectively. The most striking feature was the diffuse marked increase in amount of pericellular collagen weave fibers (endomysial matrix), parallel to the increase of heart weight. The hypertrophied myocytes were encased in a dense weave of collagen fibrils continuous with those of adjacent myocytes. The muscle fibers in hypertrophied hearts were markedly larger than normal, although this was extremely variable from an area to another. Besides, a diffuse increase in the number of thick collagen fibers constituting broad bands and sheets of collagen surrounding disorganized muscle bundles (perimysial matrix) was observed. Scattered dense scar-like foci, apparently replacing areas of myocyte loss, could be seen, mainly on the periphery of muscle bundles. This latter finding was more commonly observed among hypertrophied hearts from group 3 and, mainly, among hypertrophied hearts of group 4. Importantly, a progressive disarray of the connective tissue skeleton of the myocardium could be seen in parallel to the progressive increase of cardiac hypertrophy.
The progressive accumulation of interstitial collagen fibers in left ventricular hypertrophy, in parallel to an increase in heart weight, can be expected to contribute to a spectrum of ventricular dysfunction involving either the diastolic or systolic phase of the cardiac cycle, or both, that is associated with the greater than normal arrhythmogenic risk for a hypertensive heart. Moreover, the methodology used is useful for studying the spatial organization of the collagen fibrils of the myocardium under normal and pathologic conditions.
研究人类慢性动脉高血压所致左心室肥厚中的病理性纤维化和结缔组织基质。
对17颗人类心脏进行研究。第1组由对照心脏（4颗心脏，每颗重280±40克）组成，来自无心脏病证据且死亡诊断为非心脏性疾病的受试者。第2组（5颗心脏，每颗重440±50克）、第3组（5颗心脏，每颗重560±50克）和第4组（3颗心脏，每颗重680±60克）由有系统性高血压病史的受试者的心脏组成。所有心脏在尸检时均无瓣膜畸形且无缺血性疾病证据。采用细胞浸渍法，在去除心肌组织的非纤维成分后评估心肌结缔组织基质，留下未塌陷的基质，从而能获得更好的三维视图。心肌组织也进行了常规光镜和形态计量学研究。
第1 - 4组心脏的心肌细胞短径分别为13.7±7.8、23.7±3.4 µ m、26.6±3.7 µ m和32.8±5.8 µ m。对照组的纤维化体积分数为6.5%，而高血压心脏的纤维化体积分数根据心脏重量逐渐增加：第2、3和4组心脏分别为15.4%、22.9%和31.1%。最显著的特征是与心脏重量增加平行，细胞周围胶原纤维编织（肌内膜基质）的数量弥漫性显著增加。肥大的心肌细胞被包裹在与相邻心肌细胞连续的致密胶原纤维编织中。肥大心脏中的肌纤维明显大于正常，尽管从一个区域到另一个区域差异极大。此外，观察到构成围绕紊乱肌束的宽胶原带和片的粗胶原纤维数量弥漫性增加（肌束膜基质）。可见散在的致密瘢痕样病灶，明显替代了心肌细胞缺失区域，主要位于肌束周边。后一发现更常见于第3组的肥大心脏中，主要是第4组的肥大心脏中。重要的是，与心脏肥大的逐渐增加平行，可以看到心肌结缔组织骨架逐渐紊乱。
左心室肥厚中间质胶原纤维的逐渐积累，与心脏重量增加平行，预计会导致一系列心室功能障碍，涉及心动周期的舒张期或收缩期，或两者皆有，这与高血压心脏高于正常的致心律失常风险相关。此外，所使用的方法对于研究正常和病理条件下心肌胶原纤维的空间组织很有用。
