[Animal Modeling] - Establishment of a Chronic Myocardial Ischemia Small Pig Model with Phlegm and Blood Stasis Syndrome

  Objective: To establish a chronic myocardial ischemia model of phlegm stasis syndrome in small pigs using high-fat, intravenous injection of vitamin D3 (VD3) and isoproterenol.

  Method: 15 male Bama miniature pigs were randomly divided into a normal control (Ctr) group, a high-fat (HFC) group, and a phlegm stasis syndrome myocardial ischemia model (CMI) group, with 5 pigs in each group. The Ctr group was fed with regular feed, the HFC group was fed with high-fat feed, and the CMI group was established with a combination of high-fat diet, intravenous injection of VD3 and isoproterenol to establish a chronic myocardial ischemia model of phlegm stasis syndrome. The model was continuously established for 24 weeks, and the animal weight, electrocardiogram, activity, blood lipids, myocardial enzymes were measured, respectively Hemorheology, inflammation, cardiac index (CI), and myocardial ischemic area (MIS) were used to evaluate the establishment of the model and the pathological process of phlegm stasis syndrome.

  Results: Compared with Ctr group, weight, heart rate (HR), total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), atherosclerosis index (AI), low, medium and high shear whole blood viscosity and reducing viscosity, erythrocyte electrophoresis time (EPT), high-sensitivity C-reactive protein (hs CRP) and interleukin-6 (IL-6) levels in HFC group were significantly increased (P<0.05, P<0.01); The body weight, HR, total ST segment elevation at 24 hours (∑ ST), mean ST segment elevation within 24 hours (ST-average), activity, TC, triglycerides (TG), LDL-C, HDL-C, AI, creatine kinase (CK), lactate dehydrogenase (LDH), troponin 1 (cTn-1), low, medium, and high shear whole blood viscosity and reduced viscosity, EPT, Carson viscosity (CV), hs CRP, IL-6, CI, and MIS of the CMI group were significantly increased (P<0.05, P<0.01), while adiponectin (APN) levels were significantly reduced. P<0.05); Compared with the HFC group, the CMI group had significantly higher levels of AI, CK, LDH, cTn-1, low, medium, and high shear whole blood viscosity, EPT, CI, and MIS (P<0.05, P<0.01), and the APN level was significantly lower than that of the HFC group (P<0.05). Correlation analysis showed that MIS was associated with TC, LDL-C, AI, CK, LDH, cTn-1, APN, high, medium, and low shear whole blood viscosity, EPT, CV, hs CRP, and IL-6 (P<0.05, P<0.01). Linear regression analysis also showed that phlegm stasis was closely related to TC, LDL-C, AI, CK, LDH, cTn-1, APN, EPT, CV, hs CRP, and IL-6 (P<0.01). Further linear stepwise regression analysis showed that the evolution of phlegm stasis was closely related to TC, CK, and IL-6 (P<0.01).

  Conclusion: High fat feeding and injection of VD3 and isoproterenol can successfully establish a chronic myocardial ischemia miniature pig model with phlegm stasis syndrome, and lipid metabolism, hemorheology, myocardial enzyme metabolism, and inflammation can serve as models for phlegm stasis syndrome