疾病动物模型,心律失常 z-bio 2021-03-18 281

　　(1) Copy method

　　1) Chloroform-induced ventricular fibrillation (chloroform-induced ventricular fibrillation)

　　For mice weighing 25-30 g or more, use 3-4 ml chloroform cotton balls and place them in a 600 ml beaker (after replacement). Add 1 ml of chloroform to the mice. After stopping breathing, immediately remove the chest cavity and visually inspect the ventricles. The development of tremor. by

　　The incidence of ventricular fibrillation caused by chloroform is as follows: 40%-60% of mice weigh 18-22 g at about 3 weeks of age, 80% of 25-30 g mice weigh at 4-5 weeks of age, 40% to 90% of mice are 45g at 45-8 weeks of age, or even more, which is 100%. Therefore, each batch of animals must be screened before the experiment, and more than 80% of eligible animals will develop ventricular fibrillation.

　　2) Chloroform-adrenaline arrhythmia

　　In the experiment, the rabbit was placed supine and fixed on the operating table, the head was fixed, the electrode needle was inserted into the skin and connected to the electrocardiograph. Cover the nose and mouth with an anesthesia mask, put a cotton cloth soaked with chloroform on the anesthesia mask, and then let the rabbit inhale slowly (or slowly drip chloroform into the anesthesia mask) for inhalation anesthesia. When the corneal reflex disappears (this time we will enter the first stage of the third stage of anesthesia). After recording a normal ECG, read II. At this point, most animals have normal electrocardiograms, and a few animals have premature ventricular contractions or nodular heart rhythms. Stop using chloroform immediately and give the study drug. Five minutes later, the Reed II electrocardiogram was recorded, and 0.5 ml/kg of 0.01% epinephrine solution was quickly injected through the ear vein, and the electrocardiogram was recorded. It is immediately and continuously monitored by the oscilloscope. Record every 15 seconds for 1 minute, and then record up to 20 minutes every minute when needed. Rapid intravenous injection of adrenaline can quickly cause premature ventricular contractions, paroxysmal tachycardia, and even ventricular fibrillation caused by one or more causes. It lasted 3-7 minutes, and most animals fully recovered their sinus rhythm within 10 minutes. In a small number of animals, elevated blood pressure will reflexively stimulate the vagus nerve, slow down the rhythm of the heart and cause nodular or ventricular prolapse, and then gradually become nodular or ventricular pulsation, and sinus rhythm will recover approximately 5 minutes. After the arrhythmia returns to normal, you can take chloroform-adrenaline again for 30-60 minutes. Repeat 3 times in the same rabbit, and observe the duration of drug action. Since the dose of chloroform anesthesia has a great influence on the experimental results, the depth of anesthesia should be as constant as possible. The adrenaline injection should be rapid, and the arrhythmia should last for a short time. The time and duration of arrhythmia should be observed in time and accurately calculated. The experiment can be divided into a control group and an administration group. The treatment group can be given before the experiment or before the injection of epinephrine, followed by intravenous injection of epinephrine to compare the time and duration of arrhythmia between the two groups. The following methods can also be used to evaluate the efficacy: arrhythmia after administration is not a special effect; if compared with the control group, the arrhythmia is reduced by 80% or more, then it is effective; 50% or more is effective. If it is reduced, it is effective; if it is reduced by 50% or less, it is invalid. 3) Arrhythmia caused by adrenaline (arrhythmia caused by adrenaline) SD rats are 6 to 8 weeks old and weigh about 200 g. Rats were anesthetized with 20% ethyl urethane prepared by intraperitoneal injection at a dose of 1.2 g/kg body weight, fixed on the back, cut into the skin of the groin, separated and pierced femoral vein No. 5. Fix with scalp. A needle connected at a constant rate and an infusion pump for intravenous adrenaline administration at a constant rate. Needle electrodes are pierced under the skin of the rat's limbs and connected to the electrocardiograph and electrocardiograph. After the operation, a normal lead II electrocardiogram was recorded. Next, 1 ml of 0.9% sodium chloride solution was injected intravenously, and the injection was completed within 1 minute. Record ECG segments at 0, 1, 2, 3, 4, and 5 minutes to eliminate arrhythmia. The selected rats have a constant rate intravenous injection concentration of 0.0001 epinephrine 40 μg/kg body weight at a rate of 1 ml/min. Record the administration time, and carefully observe the changes in the animal's ECG with an oscilloscope. The ECG was recorded immediately after 30 seconds of injection and then every 10 seconds until the ECG was completely normal. Record the onset and recovery time of the arrhythmia. After a complete return to normal, intravenous epinephrine can be repeated every 10 to 20 minutes, and the record is the same as before. Observation indicators include the onset time of arrhythmia, the recovery time of arrhythmia, and the number of occurrences of ventricular premature beats.

　　(2) Model characteristics

　　Rabbit chloroform adrenaline-induced arrhythmia model animals will not die. The animals can be tested at intervals of one day or longer starting from the previous experiment, so that self-controlled experiments can be carried out. In the same animal, this method can reduce experimental errors caused by individual animal differences. When screening antiarrhythmic drugs, it is advantageous to choose small animals, which can be used for large-scale screening. This is also very easy to do without any special equipment. In addition, it is easy to observe that the incidence of ventricular fibrillation due to chloroform is high.

　　Epinephrine-induced arrhythmia model in rats. The method is simple, sensitive, short maintenance time, and can be repeated many times. The degree of arrhythmia can be controlled by increasing or decreasing the dose of epinephrine. Therefore, it is not easy to cause rapid Of tolerance. Compare

　　(3) In the case of drugs, high doses of adrenaline will directly stimulate β receptors, increase cardiac autonomy, conductivity, irritation, etc., and cause arrhythmia (ventricular ventricular contraction, ventricular tachycardia, etc.). Causes ventricular fibrillation). At the same time, a large amount of adrenaline is quickly injected into the animal's body, resulting in increased blood pressure, reflex excitement of the vagus nerve, a significant drop in heart rate, and gradual changes in the nodules or ventricular pre-diastole. The formation of nodular or ventricular rhythm ventricular systole. The combination of chloroform and epinephrine increases the toxicity to the heart.