Beeri Ronen, Yosefy Chaim, Guerrero J Luis, Abedat Suzan, Handschumacher Mark D, Stroud Robert E, Sullivan Suzanne, Chaput Miguel, Gilon Dan, Vlahakes Gus J, Spinale Francis G, Hajjar Roger J, Levine Robert A
Cardiac Ultrasound Laboratory, Cardiovascular Research Center, and Cardiothoracic Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Circulation. 2007 Sep 11;116(11 Suppl):I288-93. doi: 10.1161/CIRCULATIONAHA.106.681114.
Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model (no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling.
Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month (repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI+MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end-systolic volume [ESV; P<0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P<0.001). At 3 months, dP/dt and preload-recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to < or = 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically.
Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI.
二尖瓣反流（MR）使心肌梗死后（MI）的死亡率增加一倍。我们已经表明，在具有独立左心室至左心房MR型血流的急性心肌梗死模型（无固有MR）中，中度MR会加剧重塑。我们假设在心肌梗死后1个月修复中度MR可逆转这种重塑。
在18只绵羊中制造前壁心肌梗死，并在12只绵羊中植入左心室至左心房分流装置（反流分数为30%）。6只绵羊在1个月时关闭分流装置（修复组）。在基线时以及1个月和3个月时对绵羊进行比较。MI+MR（未修复）组和修复组的绵羊在第一个月出现重塑（左心室收缩末期容积[ESV]增加120%；P<0.01），但分流装置关闭在3个月时逆转了重塑，舒张末期容积（EDV）和ESV分别为基线的135%和128%，而未修复组分别为220%和280%（P<0.001）。在3个月时，修复组和仅心肌梗死组的dp/dt和预负荷可募集的搏功相对保持，而未修复组则下降近50%。促肥大的gp130和抗凋亡的pAkt增加，随后在未修复时降至基线以下，但在修复或仅心肌梗死时在3个月时仍保持升高。修复后，在3个月时，梗死周边和边缘区的基质金属蛋白酶-2降至未修复时的≤50%，而基质金属蛋白酶抑制剂TIMP-4显著增加。
在急性心肌梗死情况下早期修复中度MR可显著逆转原本进行性的重塑过程，左心室容积减小，收缩力相对保持，促进肥大和对抗凋亡的细胞内信号持续激活，基质蛋白水解活性降低。这些发现对于当前关于心肌梗死后修复MR的潜在益处的争议具有重要意义。
