Hong Huashan, Aksenov Sergei, Guan Xiaoming, Fallon John T, Waters David, Chen Chunguang
Cardiac Non-Invasive Laboratory, The Heart Hospital of New Jersey and Newark Beth Israel Medical Center, Newark 07112, USA.
Arterioscler Thromb Vasc Biol. 2002 Dec 1;22(12):2059-65. doi: 10.1161/01.atv.0000041844.54849.7e.
Impaired coronary blood flow (CF) or flow reserve with incomplete and delayed recovery of left ventricular (LV) function after revascularization is common in severe ischemic LV dysfunction. The underlying mechanism is not fully known. We studied structural changes of small intramyocardial coronary arteries (SIMCAs) in a pig model of chronic coronary stenosis, testing the hypothesis that microvascular remodeling develops distally to a severe epicardial coronary artery stenosis.
A total of 24 pigs were studied in 3 groups. Left anterior descending coronary stenosis was created to reduce CF by a mean of approximately 30%, producing severe regional systolic dysfunction without infarction. The stenosis was maintained for 7 days in 6 pigs (Group 1) and for 4 weeks in 12 pigs (Group 2). The control group (Group 3) consisted of 6 pigs with the same surgical procedures but without stenosis. The wall thickness (WTa) and lumen (L) diameter of SIMCA were measured, and the ratio of WTa/L and lumen area/total vessel area (% lumen) were calculated. The composition of the arterial wall was studied with cell proliferation markers Ki67 and BrdU. The immediate reduction in CF after the creation of the stenosis was similar in both study groups, but after the first week, CF decreased significantly (P<0.05) when the stenosis was maintained (group 2). The left anterior descending stenosis caused regional LV dysfunction in all pigs (groups 1 and 2). After 4 weeks of stenosis with chronic myocardial hibernation (group 2), but not after 1 week (group 1), WTa and WTa/L increased and L decreased significantly in the chronic hibernating region located distally to the stenosis, compared with both the control (group 3) and the normal region in the same pig. The mean % lumen of SIMCA per pig correlated with the CF reduction (r=0.92, P<0.001) and with myocardial fibrosis (r=0.82, P<0.01) in the 4-week stenosis group. Ki67- and BrdU-positive cells were increased in the wall of SIMCA in Group 1 and 2 compared with the control group (P<0.01 for each). The proliferated cells were stained positively with smooth muscle alpha-actin antibody.
In the chronic ischemic, hibernating myocardial region distal to a flow-limiting epicardial coronary stenosis, the small intramyocardial coronary arteries undergo remodeling, with an increase in wall thickness and a decrease in lumen. These structural changes may further restrict blood flow to ischemic myocardium and may account for the pathophysiologic impairment of CF or flow reserve after revascularization, which leads to delayed or incomplete recovery of myocardial function.
在严重缺血性左心室功能障碍中，冠状动脉血流（CF）受损或血流储备受损，且血运重建后左心室（LV）功能恢复不完全和延迟的情况很常见。其潜在机制尚不完全清楚。我们在慢性冠状动脉狭窄的猪模型中研究了心肌内小冠状动脉（SIMCA）的结构变化，检验了微血管重塑发生在严重的心外膜冠状动脉狭窄远端的假说。
共对24头猪进行了3组研究。制造左前降支冠状动脉狭窄，使CF平均降低约30%，导致严重的局部收缩功能障碍但无梗死。6头猪（第1组）的狭窄维持7天，12头猪（第2组）的狭窄维持4周。对照组（第3组）由6头接受相同手术操作但无狭窄的猪组成。测量SIMCA的壁厚（WTa）和管腔（L）直径，并计算WTa/L和管腔面积/总血管面积（管腔%）的比值。用细胞增殖标志物Ki67和BrdU研究动脉壁的组成。两个研究组在制造狭窄后CF立即降低的情况相似，但在第一周后，当狭窄维持时（第2组），CF显著降低（P<0.05）。左前降支狭窄在所有猪（第1组和第2组）中均导致局部LV功能障碍。在慢性心肌冬眠4周后（第2组），而非1周后（第1组），与对照组（第3组）和同一猪的正常区域相比，狭窄远端的慢性冬眠区域的WTa和WTa/L增加，L显著减小。在4周狭窄组中，每头猪SIMCA的平均管腔%与CF降低相关（r=0.92，P<0.001），与心肌纤维化相关（r=0.82，P<0.01）。与对照组相比，第1组和第2组SIMCA壁中的Ki67和BrdU阳性细胞增加（每组P<0.01）。增殖细胞用平滑肌α-肌动蛋白抗体染色呈阳性。
在心外膜冠状动脉狭窄导致血流受限的远端慢性缺血、冬眠心肌区域，心肌内小冠状动脉发生重塑，壁厚增加，管腔减小。这些结构变化可能会进一步限制对缺血心肌的血流供应，并可能解释血运重建后CF或血流储备的病理生理损害，这导致心肌功能延迟或不完全恢复。
