[Animal modeling - Drug efficacy evaluation] - Myocardial ischemia model induced by vascular stenosis controller

  1. Modeling material animal: Pitman Moore strain miniature pig, 7 months old, weighing 40kg; Drugs: ketamine, atropine, halothane, O2, CO2; Instruments: surgical instruments, biological function experimental systems, artificial respirators, ameroid resin vascular stenosis controllers.

  2. The modeling method involves subcutaneous injection of ketamine at a dose of 10mg/kg to induce anesthesia in the animal within a few minutes. Then, atropine (0.04mg/kg) is injected intramuscularly, and a 7.0mm tube is inserted into the trachea for anesthesia with halothane. Fluorothane is mixed with 95% O2 and 5% CO2 to achieve deep anesthesia at a concentration of 4%, followed by maintenance at a concentration of 0.5%. The entire process is performed using an artificial respirator. Shave the skin, disinfect, and monitor changes in electrocardiogram with a monitor. The surgical site is between the third rib, opening the pericardium to expose the origin of the left coronary artery. The initial part of the anterior descending collateral branch is stripped from the surrounding connective tissue, and an ameroid resin vascular stenosis controller is installed.

  The diameter of the vascular stenosis controller is 8.0mm, with a narrow inner hole with a diameter of 1.9mm and a narrow slit width of 1.0mm. Push the blood vessel into the inner hole through the narrow slit, rotate the stainless steel frame, and control the blood vessel until it cannot slide out. The ameroid resin used should be stored in a dryer to allow it to dry thoroughly. After the installation of the stenosis controller, the pericardium is sutured, the chest wall is partially sutured in three layers, the chest cavity is closed, the halothane pathway is closed, and the animal is placed back in the cage, waiting for the restoration of spontaneous breathing. After surgery, intramuscular injection of antibiotics is necessary to prevent infection.

  3. The modeling principle utilizes a vascular stenosis controller to narrow coronary arteries and induce myocardial ischemia, establishing a chronic myocardial ischemia animal model.

  4. Changes after modeling: After surgery, the levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and glutamic oxaloacetic transaminase (GOT) in the blood sharply increased, which was caused by surgical stress response. After about 10 days, the peak value was reached, and the inner orifice of the vascular stenosis controller also became thinner around this time, only half of the initial value. So about 10 days after surgery, CPK, LDH, and GOT increase, indicating that myocardial infarction is occurring, and most animals will die during this period.

  When myocardial ischemia and hypoxia occur, the first manifestation is a decrease in diastolic function of the heart, followed by a decrease in systolic function and changes in ST segment T waves on electrocardiogram. Finally, symptoms such as chest pain occurred.

  5. Precautions: Surgical instruments should be strictly disinfected to prevent surgical infections, surgical trauma should be minimized, and aseptic operation should be strictly enforced.