动物造模,药效评价,心肌缺血 z-bio 2024-07-31 462

　　(1) Copy method

　　1) Rats weighing around 200g (excluding animals with abnormal electrocardiograms) were subjected to myocardial ischemia induced by posterior pituitary hormone. The rats were injected with posterior pituitary hormone via sublingual or tail vein at a dose of 0.5 or 0.7U/kg body weight, at a rate of 5 or 10 seconds. Immediately after injection, electrocardiograms were recorded at 5, 10, 15, and 30 seconds, 1, 2, and 5 minutes (the recording time can be determined based on the abnormal situation shown on the oscilloscope). The changes in electrocardiogram of normal rats after injection of posterior pituitary hormone can be divided into two stages: the first stage: immediately after injection to 30s, T wave elevation and ST segment elevation (exceeding 0.1mV), especially around 10s, with the most significant changes; Phase 2: 30 seconds to several minutes after injection, the T wave is low, biphasic, inverted, the heart rate slows down, and the P-R and Q-T intervals are prolonged. Result determination: Positive results are considered based on the occurrence of ischemic changes in the first or second stage, otherwise negative results are considered. The differences between the groups are compared and statistically analyzed. Or take 2-3kg of healthy rabbits and drip 2.5U/kg body weight of posterior pituitary hormone at a constant rate within 10 minutes. The electrocardiogram changes can last for 15-30 minutes. In addition to the ischemic electrocardiogram changes mentioned above, occasional arrhythmias such as sinus arrhythmia, ventricular premature beats, and ventricular tachycardia may occur. The determination method is the same as that of rats.

　　2) Rats, guinea pigs, rabbits, cats, or dogs (excluding animals with abnormal electrocardiograms) were selected for induction of myocardial ischemia by isoproterenol. Rats, guinea pigs, and dogs were subcutaneously injected with isoproterenol daily at a dose of 2-8mg/kg body weight, while rabbits were given 10-16mg/kg body weight for 2 consecutive days. Within 30 minutes after isoproterenol administration, electrocardiograms were recorded every 5 minutes. After 24 hours of administering isoproterenol for the second time, record the electrocardiogram and kill the animal. Take the heart for pathological section examination. Isoproterenol can cause T wave inversion or biphasic, accompanied by ST segment elevation, sinus tachycardia (significantly increased heart rate), premature beats, or other arrhythmias. Pathological observation of the myocardium under the microscope shows infiltration of inflammatory cells and macrophages, swelling, rupture, disappearance of striations, and even dissolution of myocardial fibers, as well as occurrence of glass like and fat degeneration.

　　3) Experimental dogs with a body weight of 10-20kg induced by ergometrine were anesthetized by intravenous injection of pentobarbital sodium at a dose of 35mg/kg body weight. A catheter was inserted from the right femoral artery to the opening of the left main coronary artery, and ergometrine was injected into the main coronary artery at a dose of 0.22mg/kg body weight for 1 minute to induce coronary spasm and myocardial ischemia.

　　(2) The model features good repeatability and stability, no need for open chest surgery, and is simple and easy to implement. Among them, posterior pituitary hormone and ergometrine cause myocardial ischemia by inducing coronary artery spasm, and are suitable for studying anti myocardial ischemia drugs that dilate coronary arteries; Isoproterenol induces myocardial ischemia mainly by increasing cardiac work and oxygen consumption, and is used to study drugs that affect myocardial oxygen metabolism balance or act on beta receptors to prevent and treat myocardial ischemia. Drug induced myocardial ischemia is difficult to quantitatively observe the effect of drugs using electrocardiography alone. It is necessary to simultaneously test hemodynamics, biochemistry, and pathology to evaluate the therapeutic effect of myocardial ischemia drugs. But the equipment and technical requirements are relatively high.

　　(3) In clinical comparative medicine, myocardial ischemia is mainly caused by insufficient coronary blood supply or increased myocardial oxygen consumption. Pituitrin and ergometrine cause myocardial blood supply deficiency by inducing coronary artery spasm, but their selectivity in constricting blood vessels is poor and there are still some differences between clinical coronary artery constriction induced myocardial ischemia; Isoproterenol induces myocardial ischemia mainly by increasing cardiac work and oxygen consumption, resulting in relatively insufficient myocardial blood supply, simulating the clinical model of increased cardiac work leading to relatively insufficient blood supply in patients. The symptoms, signs, and electrocardiogram changes caused by the above model are basically similar to those of clinical human patients.