动物造模,药效评价,慢性心肌缺血 z-bio 2024-09-06 955

　　1. Modeling material animals: Healthy experimental miniature pigs, weighing (22.64 ± 4.3) kg, male or female not limited; Medications: Ketamine, Atropine, Pentobarbital, Isoflurane, Nitroglycerin, Penicillin; Equipment: ECG monitor.

　　2. Modeling method: Animals were induced to anesthesia by intramuscular injection of 10mg/kg ketamine and 0.04mg/kg atropine, followed by intravenous anesthesia with 5% pentobarbital, tracheal intubation, assisted breathing with a ventilator, inhalation of isoflurane to maintain anesthesia, and routine electrocardiogram monitoring. An incision is made on the anterior outer side of the third intercostal space on the left side, and a heart bag is cut. The starting part of the left circumflex branch is freed about 2-3cm and an ameroid constrictor ring (diameter 2-2.25cm, depending on the thickness of the artery) is inserted at this location. Continuous intravenous infusion of nitroglycerin during surgery to prevent vascular spasm. Perform a 12 lead electrocardiogram before and 1 hour after surgery. After surgery, 1.6 million units of penicillin sodium were administered via intramuscular injection twice a day for three consecutive days.

　　3. The principle of modeling is to wrap the ameroid constriction ring around the outside of the coronary artery. The ameroid constriction ring is a double-layer ring with an inner diameter of 2.0-2.5mm, consisting of an outer layer of metal, plastic, or other materials and an inner layer of casein. It will expand after absorbing water. Due to the inability of the outer layer to deform, casein can only be compressed inward after expansion, gradually narrowing the inner diameter of blood vessels. Meanwhile, due to the formation of blood clots, the narrowing of the vascular lumen can reach over 95%, leading to myocardial ischemia in animals.

　　4. Changes in electrocardiogram after modeling: One hour after the insertion of the ameroid constriction ring, no acute myocardial infarction pattern (including ST segment elevation and non ST segment elevation myocardial infarction) was observed in the electrocardiograms of all animals. After 5 weeks of insertion of the ameroid constrictor ring, most animals showed changes in electrocardiogram, mainly ST segment depression and/or T wave changes in leads I, AVI and/or II, UI, AVF and/or V4-V6.

　　Coronary angiography results: The model animals underwent coronary angiography immediately after the insertion of the ameroid constrictor ring and at 5 weeks postoperatively, and no vascular variations were found in the miniature pigs. No acute vascular occlusion was detected by immediate coronary angiography after the insertion of the ameroid constrictor ring. At 5 weeks after surgery, coronary angiography showed complete occlusion of the left eir cum lex coronary artery (LCX) in half of the animals, 99% stenosis in 35% of the animals, and 95% stenosis in 15% of the animals.

　　Cardiac magnetic resonance examination results: Compared with the results before model preparation, the data of cardiac motion function and myocardial tissue blood flow perfusion in the model animals after 5 weeks of implantation of the ameroid constrictor ring showed a significant decrease in myocardial wall thickening rate and wall motion amplitude within the LCX dominated range (left ventricular sidewall or inferior wall) in all animals; All animals showed myocardial perfusion defects within the LCX controlled area at rest and/or after loading, with some animals experiencing subendocardial myocardial infarction. No perfusion defects or myocardial infarction were observed in other walls of the left ventricle.

　　5. Pathological changes after modeling: After 5 weeks of insertion of the constriction ring, it was observed that the lumen of the constriction ring was occluded. HE staining of the left ventricular sidewall revealed degenerative changes in the myocardium, which contained a large number of degenerated and necrotic cells interwoven with normal myocardium. The middle layer of the myocardium was more significant, and no reparative fibrosis was observed.

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