动物造模,药效评价,心力衰竭 z-bio 2024-07-26 394

　　1. Modeling material animal: Healthy SD rats, male, 260-280g; Medications: Atropine, Penicillin, Ketamine/Diazepam; Equipment: BL-420 Biological Function Experiment System, Small Animal Ventilator.

　　2. Modeling method: After weighing the rats, subcutaneous injection of atropine 1mg/kg was administered to inhibit respiratory secretions, and intramuscular injection of penicillin 10000u was administered to prevent infection. After 30 minutes, ketamine/diazepam was mixed in a ratio of 100mg: 5mg, and intraperitoneal anesthesia was administered at a dose of 130mg/kg ketamine. After successful anesthesia, the tube is cut open and inserted, and a small animal respirator is connected. Tidal volume of 3-5ml, frequency of 80 times/min. Subcutaneous connection of electrocardiogram monitoring electrodes to the limbs of rats for intraoperative electrocardiogram monitoring. The mouse is placed in a supine position, the surgical area is dehulled, iodine is disinfected, sterile hole towels are laid, and a horizontal incision (1.5cm) is made in the third intercostal space of the left anterior chest. The intercostal muscles are separated and entered into the chest cavity, and an open heart is cut to expose the heart. An ophthalmic eyelid opener can be used to open the intercostal incision, and sterile forceps are used to lift the left atrial appendage, exposing the root of the aorta. Between the right ventricular outflow tract and the left atrium, 2-3mm away from the root of the aorta, a silk thread is threaded through the main trunk of the left coronary artery, and a small bundle of myocardium is tied together. The color of the myocardium below the suture becomes lighter and paler. At the same time, electrocardiogram monitoring shows a significant increase in the amplitude of the limb lead R wave. Subsequently, the ST segment of the aVL lead. After sterilization, increase the ventilation volume to 10-12 ml with a frequency of 90-100 beats per minute, fully inflate the lungs, and then gradually close the chest layer by layer. After the rats recover spontaneous breathing, the tubes are removed and they are housed in cages. Four hours after surgery, the rats are given feed and drinking water. Daily intramuscular injection of 10000u penicillin for 3 days after surgery to prevent infection. The control group underwent thoracotomy sham surgery during the same period, which involved only threading the silk thread around the left coronary artery trunk without ligation.

　　3. Modeling principle: As myocardial infarction can lead to heart failure, the method of ligating coronary arteries is used for modeling.

　　4. General changes after modeling: Five weeks after surgery, the surgical group rats showed obvious poor hair luster, rapid breathing, cyanosis, increased eyelid secretions, and decreased mobility.

　　5. Biochemical and pathological changes after modeling

　　(1) Hemodynamic changes in rats: Six weeks after left coronary artery ligation, a comparison of hemodynamics between the surgical group and the sham group showed that LVSP, LV+dp/dt max, and LV dp/dt max in the surgical group were significantly lower than those in the sham group; LVEDP， Significantly higher than the sham surgery group, both exceeding 2.0kPa. The surgical group of rats showed impaired myocardial contraction and relaxation function. There was no significant difference in heart rate between the two groups.

　　(2) Pathological changes in rats: Image analysis of cardiac pathological sections in the surgical group determined that the myocardial infarction area accounted for (42 ± 13)% of the left ventricle, while pathological sections in the sham surgery group confirmed no myocardial necrosis.

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