Surgical optimization and characterization of a minimally invasive aortic banding procedure to induce cardiac hypertrophy in mice

被引:30
作者
Martin, Tamara P. [1 ]
Robinson, Emma [2 ]
Harvey, Adam P. [2 ]
MacDonald, Margaret [1 ]
Grieve, David J. [2 ]
Paul, Andrew [1 ]
Currie, Susan [1 ]
机构
[1] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 ORE, Lanark, Scotland
[2] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland
关键词
FACTOR-KAPPA-B; PRESSURE-OVERLOAD; IN-VIVO; CARDIOMYOCYTE HYPERTROPHY; HEART-FAILURE; ACTIVATION; FIBROSIS; INFLAMMATION; DYSFUNCTION; DELTA;
D O I
10.1113/expphysiol.2012.065573
中图分类号
Q4 [生理学];
学科分类号
071003 [生理学];
摘要
Left ventricular pressure overload in response to aortic banding is an invaluable model for studying progression of cardiac hypertrophy and transition to heart failure. Traditional aortic banding has recently been superceded by minimally invasive transverse aortic banding (MTAB), which does not require ventilation so is less technically challenging. Although the MTAB approach is superior, few laboratories have documented success, and minimal information on the model is available. The aim of this study was to optimize conditions for MTAB and to characterize the development and progression of cardiac hypertrophy. Isofluorane proved the most suitable anaesthetic for MTAB surgery in mice, and 1 week after surgery the MTAB animals showed significant increases in systolic blood pressure (MTAB 110 +/- 6 mmHg versus sham 78 +/- 3 mmHg, n= 7, P < 0.0001) and heart weight to body weight ratio (MTAB 6.2 +/- 0.2 versus sham 5.1 +/- 0.1, n= 12, P < 0.001), together with systolic (e.g. fractional shortening, MTAB 31.7 +/- 1%versus sham 36.6 +/- 1.4%, P= 0.01) and diastolic dysfunction (e.g. left ventricular end-diastolic pressure, MTAB 12.7 +/- 1.0 mmHg versus sham 6.7 +/- 0.8 mmHg, P < 0.001). Leucocyte infiltration to the heart was evident after 1 week in MTAB hearts, signifying an inflammatory response. More pronounced remodelling was observed 4 weeks postsurgery (heart weight to body weight ratio, MTAB 9.1 +/- 0.6 versus sham 4.6 +/- 0.04, n= 10, P < 0.0001) and fractional shortening was further decreased (MTAB 24.3 +/- 2.5%versus sham 43.6 +/- 1.7%, n= 10, P= 0.003), together with a significant increase in cardiac fibrosis and further cardiac inflammation. Our findings demonstrate that MTAB is a relevant experimental model for studying development and progression of cardiac hypertrophy, which will be highly valuable for future studies examining potential novel therapeutic interventions in this setting.
引用
收藏
页码:822 / 832
页数:11
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