动物造模,药物损伤心功能模型 z-bio 2021-11-29 662

　　[Modeling mechanism] Commonly used drugs include pentobarbital, propranolol, verapamil, imipramine, furazolidone and allylamine. The main mechanism that causes heart failure is the inhibitory effect on the heart, such as negative frequency, negative conduction, negative muscle strength and dose. -rely. Blood vessels are over-dilated, blood pressure is reduced, coronary blood flow is reduced, and blood supply to the heart muscle is reduced.

　　[Modeling method] A healthy 9-18 kg mongrel dog was selected, intravenously anesthetized with sodium pentobarbital (30 mg/kg), fixed supine position and artificial respiration, the electrode needle was inserted into the limbs, and the electrocardiogram was measured. . Cut the skin along the center of the sternum, separate the muscle layer, and cut the costal cartilage in the fourth intercostal space at the left end of the sternum to expose the heart. Cut the heart capsule and suture the Walton-Brodie pressure gauge to the left and right ventricular walls, or implant ultrasound crystals under the ventricular membrane to record ventricular contractions and dopamine (20μg/kg intravenous injection). It is recommended to use an adjusted wall pressure gauge to generate the maximum diastolic tension energy. Close the chest cavity and re-establish negative pressure in the chest cavity. Next, the left ventricle dp/dtmax systolic blood pressure, diastolic blood pressure, central venous pressure and other indicators were measured by intubation. Alternatively, use a male Sprague Dawley rat to anesthetize the rat with an intraperitoneal injection of 20% urethane 1.2 g/kg, fix it on the operating table in a supine position, insert the needle electrode into the limbs, and guide the II ECG and Heart rate. Observed. Make a 1.5 cm longitudinal incision 1 cm below the sword, separate the duodenum, ligate the gastric pylorus, make a small incision on the surface of the duodenum (be careful not to damage the blood vessels), insert the gastric tube 2 mm thick, and ligate And fix, return the duodenum to the abdominal cavity, and suture the muscle skin. The left superficial jugular vein was separated and 1200 U/kg heparin was injected intravenously. The right common carotid artery was separated, and a heparin-filled heart catheter with an inner diameter of 1 mm coated with liquid paraffin was inserted into the left ventricle through the common carotid artery, and the other end was inserted into the left ventricle BL-420E multi-channel physiological recorder through the transducer. Observe and record your heart rhythm. The maximum rate of increase in left ventricular pressure (+dp/dtmax), the maximum rate of decrease in left ventricular pressure (-dp/dtmax).

　　(1) Propranolol induces heart failure (dogs): First, propranolol 4 mg/kg intravenously, and then propranolol 0.125-0.25 mg/kg intravenously? min, lasts 80 minutes. Animal myocardial contractility is reduced and cardiac output is reduced. Output, left ventricle dp/dtmax decreased, heart rate decreased, systolic and diastolic blood pressure decreased, central venous pressure increased, and total peripheral vascular resistance increased. Start the test after 20 minutes with Xindean. Inotropic drugs, such as intravenous injection of 1 mg/kg aminoketone, can improve heart function, but have no significant effect on contraction, relaxation and heart rhythm.

　　(2) Verapamil causes heart failure (dogs): Verapamil maintains 100μg/(kg·min) until the cardiac output is significantly reduced, and then continuously administers for 5-30 minutes, after which the dose is adjusted to 25μg/(kg Minutes) until the heart failure is stable and maintained for 20 minutes.

　　(3) Pentobarbital sodium can induce heart failure (dogs): intravenous injection of 5 mg/kg or 10 mg/kg of pentobarbital sodium every 10 minutes until heart failure occurs.

　　(4) Propafenone causes heart failure (rats): 0.35% propafenone injection 3 ml/kg rapid sublingual intravenous injection (injection should be completed within 3-5 seconds), wait for the left ventricular maximum ventricular pressure increase rate Animals dropped to 20%-40% before dosing. [Model Features] The method of establishing a drug-induced heart failure model is simple and reproducible. However, this model cannot reflect the pathological changes of clinical heart failure. [Model Evaluation and Application] The model can be used as a pharmacological tool for evaluating drugs that are toxic to the heart, and can also be used to evaluate the effects of specific cardiotonic drugs. However, because this is an acute experimental model, it does not necessarily reflect the drug's effect and treatment on chronic congestive heart failure. In addition, the effects of drugs on myocardial depression have different stages of development and disappearance, so it is necessary to choose an appropriate stage to evaluate the effects of drugs. In experiments, rapid supplementation of inhibitory drugs should be avoided.