Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury / 中华医学杂志(英文版)

BACKGROUND@#Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.@*METHODS@#Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.@*RESULTS@#Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.@*CONCLUSION@#PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

Propofol eliminates the protective effect of heart pacing-induced preconditioning on the isolated ischemic myocardium / 中华麻醉学杂志

To study the effect of propofol on the protection of ischemic isolated heart preconditioned by rapid heart pacing. Method: 24 white rabbits were assigned randomly into ischemia control (IC), pacing+ischemia (PI), and propofol+pacing+ischemia (PPI)group. Result: After 30 min of total heart isehemia followed by 30 min reperfusion, the recovery level of LVDP, LV+dp/dt max and LV-dp/dt max is much better in PI group than that of IC group (P

Myocardial uptake of thiopental in the isolated rabbit heart:the study of pharmacokinetics and pharmacodynamics / 中华麻醉学杂志

To study the dynamic process of myocardial uptake of thiopentai in the isolated rabbit hearts. Method: Thiopental at doses of 500?mol, 1500?mol and 500?mol was given sequentially to the perfused rabbit heart in a total time of 15 min. The outflow concentration of thiopental was measured with high performance liquid chromatography and the left ventricular +dp/dtmax served as a effective parameter. Resuh: The disposition and elimination of thiopental can be best described hy a two-compartment open model. It can disposed into myocardium rapidly (T_(1/2)?=0.5?0.1 min), but elimination was relatively slow (T_(1/2)?=25.3?10.1 min). The transfer rate was slower from peripheral to central compartment than from central to peripheral compartment. The tbeoritical maximum depressant effect of thiopental on + dp/dt (Emax) was 19.0 4-11.2 kPa.s~(-1) corresponding to 1/10 E_0. Conclusion: The myocardial uptake of thiopental can be fitted to a two-compartment open model with rapid disposition and relative slow elimination process.