动物造模,药效评价 z-bio 2024-08-29 453

　　Rapid atrial stimulation has various effects on the electrical activity of atrial cells, such as shortening the effective refractory period (AERP) of the atrium, increasing the heterogeneity (non-uniformity or dispersion) of AERP, and slowing down local conduction. Moreover, rapid atrial electrical stimulation significantly increases the diameter and volume of the atrium, as well as the sympathetic nerve density, thus promoting the occurrence and persistence of atrial fibrillation. Morillo et al. designed a rapid atrial pacing AF model in 1995: the animal neck and chest were routinely disinfected with a cloth, the right neck skin was cut open and subcutaneous tissue was separated, the right internal jugular vein was exposed, and a "J" - shaped umbrella shaped atrial single electrode was inserted. Under X-ray fluoroscopy, the electrode tip was fixed to the right atrial appendage, and pacing threshold, pulse width, resistance, and other parameters were measured satisfactorily. After that, the electrode tail was connected to a fixed frequency pulse generator. First, set the pacing frequency to 70 beats per minute, gradually adjust it to 400 beats per minute, and maintain the ventricular rate at around 130 beats per minute with a pacing pulse width of 2 milliseconds. After the electrocardiogram examination showed that the pacemaker was working normally, the pulse generator was buried in the neck pocket and the incision was sutured. The pacing was continued for about 6-8 weeks (if stimulated at a frequency of 600-800 times/division, the duration of pacing could be reduced to 1-2 weeks), followed by programmed stimulation (S1S2S3~S1S2S3S4) or Burst stimulation. The S1S2 cycle is 400 milliseconds or 300 milliseconds, and the S1S2 interval is 30 milliseconds longer than the atrial effective refractory period. The starting interval of S2S3 is equivalent to 80% of the base cycle and decreases in steps of 10 milliseconds. If S1S2S3 stimulation cannot induce AF, then S1S2S3S4 stimulation is introduced, and the initial interval and decreasing step size of S3S4 are the same as S2S3 stimulation. If S1S2S3S4 stimulation still cannot induce AF, give a Burst stimulation of 20-30 seconds with a circumference of 100 milliseconds. After the above stimulation, most models can induce AF. This method has a high success rate in establishing a chronic persistent AF model and a long duration of AF maintenance. It is the most mature and widely used method for studying the mechanism and treatment of non valvular AF. However, this method may encounter unexpected situations such as pacemaker electrode detachment leading to model establishment failure, intraoperative induction of ventricular fibrillation resulting in sudden animal death, thromboembolism, and unstable pacemaker operation. Therefore, it is necessary to provide electrocardiographic monitoring during the surgical process and conduct regular surface electrocardiography and echocardiography examinations after surgery to monitor the safety of the animals and ensure the successful establishment of the model. When preparing AF models using rapid pacing in Sichuan, attention should also be paid to controlling ventricular rate, as excessively fast ventricular rate can cause ventricular dysfunction and lead to atrial changes unrelated to rapid atrial pacing.