Sakaguchi G, Young R L, Komeda M, Yamanaka K, Buxton B F, Louis W J
Departments of Clinical Pharmacology and Therapeutics and Cardiac Surgery, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia.
J Thorac Cardiovasc Surg. 2001 Apr;121(4):750-61. doi: 10.1067/mtc.2001.112462.
This study examined the effects of aneurysm repair in a rat model of myocardial infarction on functional indices and on the spatiotemporal distribution of cardiac contractile protein and natriuretic peptide messenger RNA.
In a rat infarct model, expanded left ventricular aneurysms were plicated 4 weeks after infarction. At 30 weeks, transverse heart sections were taken at 4 levels (apex [level 1] through base [level 4]) and assessed by in situ hybridization histochemistry to determine regional messenger RNA levels of pre-pro-atrial natriuretic peptide, cardiac alpha-actin, skeletal alpha-actin, myosin light chain-2v, and beta-myosin heavy chain.
Rats with plicated left ventricular aneurysms had reduced left ventricular endocardial circumference (19%, P <.005), lower heart weight ratio (31%, P <.05), left ventricular end-diastolic pressures (51%, P <.05), and increased +/-dP/dt (34%-38%, P <.05). Cardiac messenger RNA levels of pre-pro-atrial natriuretic peptide were reduced in the septum (levels 2 and 3), and skeletal alpha-actin levels were reduced in the septum and left ventricular free wall of plicated rats (level 3). beta-Myosin heavy chain levels were markedly reduced in peri-infarct regions of the left ventricular free wall, septum, and right ventricle in plicated rats at level 4, whereas myosin light chain-2v levels were reduced at levels 2 and 4 in the left ventricular free wall and at level 4 in the right ventricle.
Plication of left ventricular aneurysm after infarction in the rat significantly reduced cardiac hypertrophy, improved cardiac function, and reduced the upregulation of pre-pro-atrial natriuretic peptide and both fetal and adult contractile protein isoforms associated with cardiac hypertrophy.
本研究在大鼠心肌梗死模型中检测动脉瘤修复对功能指标以及心脏收缩蛋白和利钠肽信使核糖核酸时空分布的影响。
在大鼠梗死模型中，梗死4周后对扩张的左心室动脉瘤进行折叠处理。30周时，在4个水平（从心尖[水平1]至心底[水平4]）获取心脏横切面，通过原位杂交组织化学进行评估，以确定前心钠素原、心脏α-肌动蛋白、骨骼肌α-肌动蛋白、肌球蛋白轻链-2v和β-肌球蛋白重链的区域信使核糖核酸水平。
左心室动脉瘤折叠处理的大鼠左心室内膜周长减小（19%，P<.005），心脏重量比降低（31%，P<.05），左心室舒张末期压力降低（51%，P<.05），且±dP/dt增加（34%-38%，P<.05）。折叠处理大鼠的室间隔（水平2和3）前心钠素原的心脏信使核糖核酸水平降低，折叠处理大鼠的室间隔和左心室游离壁（水平3）骨骼肌α-肌动蛋白水平降低。在水平4，折叠处理大鼠的左心室游离壁、室间隔和右心室梗死周边区域β-肌球蛋白重链水平显著降低，而左心室游离壁的水平2和4以及右心室的水平4肌球蛋白轻链-2v水平降低。
大鼠梗死后左心室动脉瘤折叠处理可显著减轻心脏肥大，改善心脏功能，并减少与心脏肥大相关的前心钠素原以及胎儿和成人均收缩蛋白亚型的上调。
