动物造模,药效评价,充血性心力衰竭 z-bio 2024-07-23 302

　　1. Modeling material animal: New Zealand white rabbit, 16-20 weeks old, male, weighing 2.1-3.3kg; Medications: Su Mian Xin, Penicillin, Ketamine/Diazepam; Instrument: BL-420 Biological Function Experiment System.

　　2. Modeling method: After weighing the rabbit, inject 0.1ml/kg of Su Mian Xin intramuscularly. After satisfactory anesthesia, fix the rabbit in a supine position on the operating table. Shave the chest, disinfect it regularly, and then lay a sterile hole towel. Cut open the skin and muscles along the midline of the sternum, and closely adhere to the left edge of the sternum to cut open the 2nd to 3rd or 3rd to 4th rib cartilage (be careful to avoid pneumothorax). Use a small hook to gently open the chest cavity, being careful not to damage the pleura. Use a small curved forceps to gently lift and carefully cut the pericardium, suspending the pericardium under the skin to fully expose the heart. Gently lift the left atrial appendage with toothless forceps, locate the starting point of the left coronary artery to the left along the left atrial appendage, and ligate the coronary artery at a distance of 3mm from the opening of the coronary artery at the root of the aorta in the anterior descending branch of the left coronary artery. Observe with the naked eye that the color of the blood supply area of the coronary artery becomes darker and the pulsation weakens. If there is no such change, ligate the blood vessel again to ensure sufficient myocardial necrosis. Then, connect the limb guide and chest lead to record the surface electrocardiogram at a speed of 50mm/s. The electrocardiogram shows ST segment arched upward to determine the success of the myocardial infarction (MI) model. Close the chest and place a No.14 scalp needle catheter connected to a 10ml syringe in the pericardial cavity. After closing the chest, remove the residual gas in the pericardial cavity and remove it. Intramuscular injection of 1g piperacillin to prevent wound infection. After the surgery, place the rabbit on its side to keep warm and wait for anesthesia to awaken before returning it to the rabbit cage. Three weeks after surgery, electrocardiogram examination showed pathological 0 waves in the relevant leads of the coronary artery ligation group, while there were no abnormal changes in the sham surgery group, proving the success of the myocardial infarction model.

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

　　4. Changes after modeling: Three weeks after surgery, the left ventricular diastolic dimension (LVDD) and left ventricular end systolic dimension (LVSD) in the heart failure group were significantly increased compared to the sham surgery group, while the left ventricular shortening fraction (FS) and left ventricular ejection fraction (LVEF) were significantly reduced, indicating left ventricular systolic dysfunction in the heart failure group. The results at 15 weeks after surgery were the same as those at 3 weeks after surgery.

　　Hemodynamic examination showed that the heart failure group had a decrease in the maximum ascending and descending rates of the left ventricle compared to the sham surgery group, accompanied by an increase in end diastolic pressure and a decrease in end systolic pressure, indicating myocardial dysfunction in rabbits with acute myocardial infarction after coronary artery ligation.

　　Gross observation of infarct area in the heart. The sham surgery group had no myocardial infarction; In the heart failure group, the infarction foci were mainly distributed in the left ventricular anterior wall and lateral wall, and all were transmural infarctions. The average infarct area at the papillary muscle level was 22.3% (19.0% to 30.6%).

　　5. Precautions: During anesthesia, due to the large individual differences in rabbits, the new dose of rapid sleep should be individualized, and close observation of breathing, heartbeat, corneal reflex, and response to pain should be conducted. Otherwise, it may lead to respiratory depression and even death; Surgical thoracotomy should be performed at the midline of the sternum, and then 2-3 or 3-4 ribs should be cut tightly against the left edge of the sternum. This can effectively avoid damaging the pleura without causing pneumothorax. If pneumothorax occurs during surgery, the experiment should be completed quickly, the chest cavity should be closed, and air should be extracted from the affected side of the chest cavity to assist in lung expansion; The tissue of the left atrial appendage is relatively fragile. When pulling the left atrial appendage, the tension should be moderate. If it is too loose, it cannot expose the anterior descending branch well. If it is too tight, it can cause significant damage to the left atrial appendage, sometimes crushing it and leading to the death of the rabbit; After ligation, an electrocardiogram should be performed to confirm the successful preparation of the acute myocardial infarction (MI) model if the sT segment shows an upward arch shape. If it does not appear, a second ligation can be performed, but generally not more than three times, to avoid excessive damage to the myocardial tissue; When ligating, attention should be paid to the variation of the anterior descending branch of the coronary artery to avoid missed ligation and unsuccessful model; Strictly follow aseptic procedures during the operation, and administer 40-60ml of intravenous fluid (5% GNS) appropriately. Administering antibiotics once after surgery to prevent infection has a high survival rate for animals.