疾病动物模型,心律失常,犬缺血心脏 z-bio 2021-03-18 644

　　(1) Reproduction method For experimental dogs weighing 12 to 15 kg, use 3% sodium pentobarbital at a dose of 30 mg/kg body weight for intravenous or intraperitoneal injection anesthetize, cut open the mid-neck skin, separate the trachea for endotracheal intubation, and connect Perform artificial respiration with an artificial ventilator, then cut along the fourth intercostal space on the left, open the chest cavity, expose the heart, separate the left anterior descending coronary artery (LAD) at the tip of the left atrial appendage 0.5cm, and put it together with the No. 5 injection needle After ligation, the needle was withdrawn and the LAD was incompletely ligated; 20 minutes later, the LAD was completely clamped with an arterial clip, and the collateral circulation formed by the lower blood vessel and the blunt marginal branch of the coronary circumflex branch was sutured with a noninvasive suture needle ; 2h later, loosen the arterial clamp to resume perfusion. 5 to 8 days after the operation, the dog was anesthetized again, ventilated, the chest was opened in the same way as above, and the left femoral vein was separated for infusion, maintaining PaO24.5-6kPa, pH 7.4, rectal temperature 38-39℃, right femoral artery cut Open intubation to monitor blood pressure, insert 8 to 10 myocardial monopolar stimulation electrodes with an outer diameter of 0.2mm (surface insulated, with a small hook at the front) respectively into the left ventricular infarction area and the adjacent normal area, optional 4-6 Stroke-controlled stimulation of each part, the minimum voltage that causes more than 8 ventricular beats is the diastolic excitement threshold (DET), and then double DET is the basis for stimulation (S1), the wave width is 2ms, and the interval (S1～S2) Is 30ms. After 8 S1s, 1 (S2), 2 (S2S3) and 3 (S2S3S4) pre-period stimuli were given in sequence, and each pre-period stimulus was subjected to diastolic negative scanning at 10ms steps until the effective refractory period ( ERP), the programmed stimulation is carried out to induce ventricular tachycardia or ventricular fibrillation. The induced ventricular tachycardia is terminated with short bursts of ventricular overspeed stimulation, and ventricular fibrillation is defibrillated with direct current epicardium, and the required power is 15-20mA. Program-controlled ventricular stimulation was performed before and after the medication, and the position and degree of the ventricular stimulation were unchanged. After the medication, the no longer induced ventricular tachycardia or ventricular fibrillation was used as a marker of efficacy.

　　(2) Model characteristics This model making method can repeatedly induce ventricular tachycardia and ventricular fibrillation in model animals. The disadvantage is that the model preparation method is more complicated, and the need for surgical thoracotomy will cause great damage to the animal, but the model has a high success rate and good reproducibility. It is still a comparison to explore the pathological mechanism of ventricular tachycardia and ventricular fibrillation after myocardial infarction and to screen new anti-arrhythmic drugs. Ideal pharmacology experimental model.

　　(3) Comparative medicine This method uses Harris two-stage ligation with partial reperfusion and anastomotic branch suture method to cause acute anterior wall myocardial infarction in dogs. After 5-8 days, the dog’s spontaneous arrhythmia disappears and can be repeatedly induced by ventricular programmed stimulation. Rapid ventricular arrhythmia, the main mechanism of arrhythmia is the formation of reentry, and the pathological changes caused by repetitive arrhythmia are very similar to the clinical ones. Therefore, this method has similar electrophysiological and histological characteristics with recurrent ventricular tachycardia and ventricular fibrillation of clinical myocardial infarction, and the pathological morphology is very similar.