【Animal Modeling】-A model of myocardial infarction caused by electrical stimulation of the canine coronary artery

  (1) Reproduction method After weighing, the experimental dogs were anesthetized with 3% sodium pentobarbital at a dose of 30 mg/kg intravenously and inserted into the tracheal tube. The animal was fixed in the right decubitus position, and the femoral artery and the femoral vein were separated. They were used to measure peripheral arterial pressure, give test samples and supplement anesthesia [3% sodium pentobarbital 10ml add 500ml normal saline, and 5ml/(kg· h) the speed of giving]. Separate the right jugular vein cannula for intravenous infusion of heparin. Open the chest from the 4th and 5th intercostal space, cut the open bag, expose the heart, separate the left circumflex branch (LCX), from the root to the first main branch, and ligate the other small branches, the separation length is nearly 2cm, and the appropriate electromagnetic hook The flowmeter probe (about 2mm) continuously records the blood flow of the left circumflex branch. Thread a thin silk thread under the LCX, lift the silk thread to block the blood flow for 20 seconds, observe and record the flow change. Put down the silk thread to fully fill the blood and use this flow as the peak flow. Place 2 to 3 small silver clips on the LCX and adjust the silver clips to reduce the blood flow to about 30% of the peak flow (this test reduces to about 8ml/min). When the flow is relatively stable, the electric stimulation can be started. The electrical stimulation needle is made of stainless steel, and the electrode tip penetrates the LCX blood vessel wall, extends into the lumen and is fixed to ensure that the tip is in close contact with the artery intima. Electrical stimulation with a direct current of 150μA, continued until the LCX blood flow decreased to 0, and continued for 3 minutes. The electrical stimulation time was at least 15 minutes, and this time was recorded as the occurrence time of blood flow blockage. When screening samples, the observed recanalization time after administration is the time from the start of administration until the LCX flow rate is restored to 1/3 of the flow before electrical stimulation; the re-blocking time is the time from the recanalization time to when the LCX flow rate decreases to 0 again . At the end of the experiment, the animals were sacrificed, the LCX segment was cut long enough and cut open, the thrombus was removed and its wet weight was weighed.

  (2) Features of the model This model requires thoracotomy, which is difficult to operate, but is easy to locate accurately. The model has a high success rate and good stability. It is mainly used for the screening and pharmacodynamic evaluation of coronary thrombolytic drugs. The coronary artery obstruction and recanalization are judged by observing the coronary artery flow, and the indicators are objective. In the process of modeling, animals are prone to ventricular arrhythmia leading to ventricular fibrillation, which requires monitoring and defibrillation.

  (3) Comparative Medicine Clinical studies have shown that almost all myocardial infarctions, especially elderly patients, are mainly caused by coronary atherosclerosis, and occasionally by coronary embolism, inflammation, and congenital malformations. In 85%-95% of autopsy cases of acute myocardial infarction, occlusive thrombus can be found in the coronary arteries. On the basis of coronary atherosclerosis, once hemorrhage or persistent vascular spasm or thrombosis occurs in or under the atherosclerotic plaque, the coronary arteries are completely occluded, leading to myocardial infarction. This model adopts thoracotomy to stimulate the left circumflex coronary artery in animals with acute myocardial infarction and the clinical pathogenesis is similar. However, thoracotomy itself can cause a series of pathophysiological changes in animals, which are partly different from clinical acute myocardial infarction, but the results of myocardial pathology and electrocardiogram changes show similar to clinical acute myocardial infarction patients.