【Animal Modeling】-The pharmacological model of delayed depolarization of cardiomyocytes and triggering arrhythmia

  (1) Reproduction method The guinea pig weighing 200~300g is stunned with a blunt instrument, and the heart is quickly taken out. In the oxygen-rich Tris-Tai's solution (NaCl 137mmol/L, KCl 5.4mmol/L, CaCl22.3mmol/L, MgCl21.05mmol/L, NaHCO31.2mmol/L. Glucose 11.2mmol/L, Tris5.0mmol/L, pH 7.4) Separate the left ventricular papillary muscle from a petri dish, fix it in a special glass bath, and use Tris-set The perfusion of the solution is 4ml/min, the temperature is maintained at 37°C, and 95% O2 + 5% CO2 is passed through. After stabilizing for 20 minutes, give a square wave stimulation. The basic circumference of the stimulation is 800ms, the wave width is 2ms, and the intensity is twice the threshold intensity. The transmembrane potential is recorded with a glass microelectrode. The microelectrode is connected to the microelectrode amplifier with A9-AgCL filament. After zooming in, one way is imported into a two-wire oscilloscope for observation, and the other way is imported into a microcomputer recording system for recording. First record the waveform of the control transmembrane action potential of the specimen perfused with normal Tris-Ty's solution, and then perfusion with 0.1~0.5μmol/L ouabain or 0.5~2μmol/L isoproterenol or ≥10mmol/L Ca2+ Fluid perfusion was performed to observe the appearance of action potential waveform, DAD and trigger arrhythmia (premature ventricular beats, dual rhythm, triple rhythm, ventricular tachycardia, etc.) within 1.5 hours of adding the above-mentioned drugs.

  (2) Model features Cardiac glycosides and other drugs can cause excessive intracellular Ca2+ and induce Na+ transient influx to cause delayed depolarization (DAD) and even trigger arrhythmia. This method uses standard microelectrode technology to record guinea pig papillary muscles Action potential, combined with ouabain or isoproterenol to observe the effect of drugs on DAD and triggered arrhythmia. An in vitro experimental model for studying the electrophysiological basis of arrhythmia.