Gaudron P, Hu K, Schamberger R, Budin M, Walter B, Ertl G
Department of Medicine, Julius-Maximilians-University, Würzburg, Germany.
Circulation. 1994 Jan;89(1):402-12. doi: 10.1161/01.cir.89.1.402.
Remodeling of infarcted and noninfarcted ventricular regions, infarct expansion, shape distortion, and global left ventricular (LV) dilation influence LV performance and survival. The effect of chronic exercise, initiated early or later after infarction, on remodeling, hemodynamics, and survival has not been studied.
A total of 156 rats were randomized after coronary artery occlusion or sham operation to remain sedentary or to start with swim training 4 days or 21 days after coronary occlusion, which was continued over 8 weeks (6 days per week, 90 minutes per day). These intervals after coronary artery ligation were chosen because final size of infarction is well reached after 4 days; histological evolution of scar healing is still in progress, and after 21 days, histological scar healing is completed. At 8 weeks, hemodynamics were measured and LV dilation quantitated by passive pressure-volume curves. In groups with small (< or = 35%) and large (> 35%) infarcts, the area enclosed by endocardial circumference, infarct size, LV diameter, scar thickness, and septal thickness were measured in stained transverse serial LV sections to assess aneurysmal shape distortion and the response of infarcted and noninfarcted myocardia. Survival was not influenced by infarction or exercise alone. In rats with small infarcts, LV volume and shape and long-term survival were not altered by chronic exercise initiated early or late after coronary artery ligation. Mortality rose in animals with large infarction as a result of exercise (P < .0001) and was 47.6% with early exercise and 26.7% with late exercise (P < .05, early versus late). Infarct size in rats with early exercise (48 +/- 3%) was similar compared with infarct size of rats with late exercise (46 +/- 2%, P = NS compared with early exercise). Exercise did not affect LV dysfunction (assessed by systolic and end-diastolic pressures and dP/dtmax) in survivors of small and large infarctions. LV volumes increased (P < .05) in sedentary rats by large infarction (n = 13, 0.48 +/- 0.04 mL) compared with volumes after sham operation (n = 33, 0.33 +/- 0.03 mL) and with exercise (early, n = 11, 0.56 +/- 0.04 mL; late, n = 11, 0.65 +/- 0.04; P < .05 versus sedentary). In nonsurvivors from early exercise, the area enclosed by LV endocardial circumference (which corresponds to LV volume) was increased by 195%, LV diameter was increased by 60%, and scar thickness was reduced by 37% (P < .05 versus respective control). Septal thickness increased in survivors by exercise (+25%) but decreased (-28.6%) in nonsurvivors (P < .0001 versus respective control).
Endurance training in rats after small infarction, whether started early or late after left coronary artery ligation, was well tolerated without changes in LV volume, shape, hemodynamics, and long-term survival. Endurance training in rats with large infarction decreased overall survival (P < .0001). In survivors from late exercise, training caused aggravation of global LV dilation without additional shape changes. Endurance training after large infarction caused aggravation of remodeling to a degree that was not compatible with life in 27% of the rats with late exercise and in 48% with early exercise after coronary artery ligation, despite similar exercise. This was explained by extensive remodeling that was most pronounced in nonsurvivors from early exercise. In these rats, severe global LV dilation, distortion of LV shape, scar thinning, and a paradoxic reduction of septal thickness, ie, mismatch of infarcted and noninfarcted myocardia, were observed.
梗死和未梗死心室区域的重塑、梗死扩展、形状畸变以及左心室（LV）整体扩张会影响左心室功能和生存率。关于梗死后早期或晚期开始的慢性运动对重塑、血流动力学和生存率的影响尚未进行研究。
总共156只大鼠在冠状动脉闭塞或假手术后被随机分组，分别保持久坐不动，或在冠状动脉闭塞后4天或21天开始进行游泳训练，并持续8周（每周6天，每天90分钟）。选择这些冠状动脉结扎后的时间间隔是因为4天后梗死最终大小已基本形成；瘢痕愈合的组织学演变仍在进行中，而21天后，组织学瘢痕愈合已完成。在8周时，测量血流动力学，并通过被动压力-容积曲线对左心室扩张进行定量分析。在梗死面积小（≤35%）和大（>35%）的组中，在染色的左心室横向连续切片中测量心内膜周长所围成的面积、梗死面积、左心室直径、瘢痕厚度和室间隔厚度，以评估动脉瘤形状畸变以及梗死和未梗死心肌的反应。生存率不受梗死或单独运动的影响。在梗死面积小的大鼠中，冠状动脉结扎后早期或晚期开始的慢性运动不会改变左心室容积、形状和长期生存率。在梗死面积大的动物中，运动导致死亡率上升（P<.00），早期运动组死亡率为47.6%，晚期运动组为26.7%（早期与晚期相比，P<.05）。早期运动大鼠的梗死面积（48±3%）与晚期运动大鼠的梗死面积（46±2%，与早期运动相比P=无显著性差异）相似。运动对小面积和大面积梗死幸存者的左心室功能障碍（通过收缩压和舒张压以及最大dp/dt评估）没有影响。与假手术组（n=33，0.33±0.03 mL）和运动组（早期，n=11，0.56±0.04 mL；晚期，n=11，0.65±0.04 mL；与久坐不动组相比P<.05）相比，久坐不动的大面积梗死大鼠（n=13，0.48±0.04 mL）左心室容积增加（P<.05）。在早期运动的非幸存者中，左心室心内膜周长所围成的面积（相当于左心室容积）增加了195%，左心室直径增加了60%，瘢痕厚度减少了37%（与各自对照组相比P<.05）。运动使幸存者的室间隔厚度增加（+25%），但使非幸存者的室间隔厚度减少（-28.6%）（与各自对照组相比P<.0001）。
小面积梗死大鼠进行耐力训练，无论在左冠状动脉结扎后早期还是晚期开始，耐受性良好，左心室容积、形状、血流动力学和长期生存率均无变化。大面积梗死大鼠进行耐力训练会降低总体生存率（P<.0001）。在晚期运动的幸存者中，训练导致左心室整体扩张加重，但无额外的形状改变。大面积梗死大鼠进行耐力训练会导致重塑加重，在冠状动脉结扎后晚期运动的大鼠中有27%、早期运动的大鼠中有48%出现这种情况，尽管运动情况相似，但这与生命不相容。这可以通过广泛的重塑来解释，这种重塑在早期运动的非幸存者中最为明显。在这些大鼠中，观察到严重的左心室整体扩张、左心室形状畸变、瘢痕变薄以及室间隔厚度反常减少，即梗死和未梗死心肌不匹配。
