动物造模,心律失常 z-bio 2021-03-18 441

　　(1) Reproduction method Experimental dogs weighing 10～13kg were anesthetized by intravenous injection of 3% sodium pentobarbital at a dose of 30mg/kg body weight, and artificial respiration was performed by endotracheal intubation. The respiratory rate was 24b/min and the respiratory ratio was 1. : 1.5, adjust the tidal volume to a positive breathing pressure of 20cmH2O. Under aseptic conditions, open the chest from the 3rd and 4th intercostal space on the left, cut the pericardium 2cm along the side of the vagus nerve, and suture the edge of the pericardium to the chest wall, exposing the left anterior wall of the heart, and descending branches in front of the left coronary artery. Separate the coronary arteries between 1 and 2 branches, put in two silk threads, according to the Harris two-step ligation method, before ligation, inject lidocaine intravenously to prevent ventricular fibrillation. When ligating for the first time, pierce a No. 5 injection needle together, and then The needle was removed, and 30 minutes later, the coronary artery was tightly ligated for the second time. Suture the pericardium, close the chest cavity layer by layer, and resume normal breathing. After 20 hours of ligation, operating dogs showed frequent and multi-source alternating nodular rhythms, ventricular premature beats, and ventricular tachycardia. This arrhythmia can be maintained until 48h later. 24h after the operation, the dog was awake and lying on his side. The electrocardiogram Ⅰ, Ⅱ, Ⅲ, aVR, aVL and aVF were continuously observed with a multi-channel electrocardiograph, and a Holter recorder could also be used for continuous recording. The method of administration can be from the dorsal vein or saphenous vein injection from outside the hind limbs of the dog. For example, if lidocaine is used as a positive control, the time for arrhythmia to return to normal is usually less than 1 hour, and many drugs do not last long on this model. Therefore, it can be administered repeatedly or drawn by the cumulative dose method. The observation indicators are total heart rate and sinus heart rate. The percentage of sinus rhythm can be calculated. The average value of the difference before and after the administration group is compared with the difference at the same time point in the control group by t test.

　　(2) Model characteristics The majority of experimental animals using this method can have more than 70% of ectopic ventricular rhythms. Depending on the location and degree of ligation, there are still a large number of nodular rhythms. In the process of model making, the use of Harris two-step ligation method can greatly reduce the mortality of animals during surgery. For example, intravenous injection of 5 mg/kg body weight lidocaine during the first ligation can significantly reduce the occurrence of ventricular fibrillation during surgery. The anterior descending branch of the left coronary artery in experimental dogs has a large variation, and some dogs have a very high position of the second branch. For example, the incidence of ventricular fibrillation in animals before ligation is very high. You can choose to ligate between the second and third branches. , And then ligate the small branches that develop downward on the second branch. Ventricular ectopic heart rhythm usually peaks after 20 hours after the second ligation. Without treatment, the ectopic heart rhythm can last for 2 to 4 days, but it is not very stable after 48 hours. Moreover, the incidence of arrhythmia is obviously related to the animal's stress state, so this experiment should be carried out in a quiet environment, and the animal is best separated from the observer. Drug experiments can be carried out 24h after surgery. This model can cause myocardial infarction in animals to a certain extent, leading to death, and animals are also prone to infection after surgery, so the success rate of the model is low.

　　(3) Comparative medicine Coronary artery ligation causes myocardial ischemic infarction to induce arrhythmia, which is the result of unidirectional conduction block and excitatory reentry due to conduction disorders. It is very similar to arrhythmia in patients with clinical acute myocardial infarction. The antiarrhythmic drugs studied by this model have great value in the clinical prevention and treatment of arrhythmias caused by acute myocardial infarction.