Experimental research on establishing chronic ischemic heart failure model of minipig with intracoronary perfusion of plastic microspheres by catheterization

Abstract

To establish a stable chronic ischemic heart failure (CIHF) model of minipig caused by gradual myocardial ischemia and necrosis that was achieved with repetitive microspheres perfusion in left anterior descending artery (LAD). A total of fifteen Wuzhishan minipigs original in Hainan China (8 to 11 months old with body weight of 20 to 30 kg) were used. The 4F angiographic catheter was superselectively engaged in LAD, and 1 ml of suspending plastic microspheres fluid were given repeatedly at ten-minute intervals, which include microspheres 1.0 x 10(5)/ml, until LVEDP raising and maintaining from 15 mm Hg to 18 mm Hg and TIMI flow was less than or equal to grade 2. Electrocardiography, hemodynamic parameters, CK-MB and cTnT were monitored during the procedure. LVEF was repeatedly measured with ultracardiography at 10 d, 20 d, 30 d, 40 d, 50 d, 60 d after establishing chronic ischemic heart failure model. Meanwhile, hemodynamic indices including mRAP, mRVP, mPAP, PCWP and CO (thermo-dilution method) were measured before and two months after procedure. The success rate, stability and repetition of chronic ischemic heart failure model were identified and evaluated. Finally, myocardial infarcted area was measured and myocardial pathologic examination was investigated. Eleven minipigs survived two months after procedure. There were ten minipigs accorded with the criteria (LVEDP > 18 mm Hg CO reduced by 30%) of the CIHF model and the success rate was 66.7% with a mean of 3.2 +/- 0.9 times of microspheres injections and total doses of (3.2 +/- 0.9) x 10(5) microspheres. This resulted in 38.5% reduction in LVEF, 197.8% elevation in LVEDP and 46.8% declining in CO from baseline values (P < 0.01), while mRAP, mRVP, mPAP and PCWP increased significantly as compared with those before procedure. Cross myocardium pathology showed the ratio of necrosis area to left ventricle (LV) area was 25.4% - 34.9% (mean 28.6%) and light microscopy examination of LV myocardium revealed that intravascular semitransparent plastic microspheres distributed throughout subendocardium of left ventricular anterior and apical parts, with more numerous focal myofiber necrosis, which characterized by pathologic founding of ischemic necrosis of myocardium with fibre proliferation. A stable CIHF model could be established in Chinese Wuzhishan minipigs with intra-coronary microspheres perfusion via superselectively engaging in LAD, which was prior to those of drug-induced, tachycardia-pacing induced or coronary artery ligation-induced, and had the advantages of stability, closed chest, mild trauma higher success rate and easy for repetition. It might be suitable for using the research of CIHF as large reliable experimental animal model.