McGarvey Jeremy R, Kondo Norihiro, Witschey Walter R T, Takebe Manabu, Aoki Chikashi, Burdick Jason A, Spinale Francis G, Gorman Joseph H, Pilla James J, Gorman Robert C
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
Ann Thorac Surg. 2015 Feb;99(2):597-603. doi: 10.1016/j.athoracsur.2014.09.014. Epub 2014 Dec 15.
There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model.
Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 μL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content.
Global and regional left ventricular functions were depressed in all infarcted subjects at 1 week compared with healthy controls. By 4-weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared with infarcted controls (ejection fraction 0.485 ± 0.019 vs 0.38 ± 0.017, p < 0.01). Similarly, regional borderzone radial contractile strain (16.3% ± 1.5% vs 11.2% ± 1.5%, p = 0.04), MR grade (0.4 ± 0.2 vs 1.2 ± 0.2, p = 0.04), and infarct thickness (7.8 ± 0.5 mm vs 4.5 ± 0.2 mm, p < 0.01) were improved at this time point in the treatment group compared with infarct controls.
Calcium hydroxyapatite injection after MI progressively improves global left ventricular function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is a viable alternative in the current management of heart failure.
心肌梗死（MI）后持续需要能够逆转或减轻重塑过程的治疗方法。在本研究中，我们评估了羟基磷灰石微球凝胶对猪MI模型中局部应变、整体心室功能和二尖瓣反流（MR）的纵向影响。
纳入25只约克夏猪。5只为体重匹配的对照猪。20只通过直接结扎旋支动脉及其分支进行后外侧梗死。梗死动物随机分为以下4组：1周治疗组；1周对照组；4周治疗组；4周对照组。梗死后，动物在梗死区内接受20次150μL羟基磷灰石凝胶或盐水注射。在各自的时间点，收集超声心动图、心脏磁共振成像和组织，以评估MR、局部和整体左心室功能、壁厚和胶原含量。
与健康对照相比，所有梗死受试者在1周时整体和局部左心室功能均降低。梗死4周后，与梗死对照组相比，羟基磷灰石组的整体功能有显著改善（射血分数0.485±0.019对0.38±0.017，p<0.01）。同样，在该时间点，治疗组的局部边缘区径向收缩应变（16.3%±1.5%对11.2%±1.5%，p=0.04）、MR分级（0.4±0.2对1.2±0.2，p=0.04）和梗死厚度（7.8±0.5mm对 4.5±0.2mm，p<0.01）与梗死对照组相比有所改善。
MI后注射羟基磷灰石可逐渐改善整体左心室功能、边缘区功能和二尖瓣反流。使用新型生物材料增强梗死物质特性是目前心力衰竭管理中的一种可行替代方法。
