The Study Of Thiazolidinedione (Rosiglitazone) On Isolated Rat Hypertrophy Myocardial Ischemia Reperfusion Injury Protective Effect

【Background】Previous Studies have shown that hypertrophied myocardium has nonuniform electrophysiologic propertie and electrotonic interaction compared with normal myocardium. Hypertrophied hearts have been demonstrated to have an increased vulnerability to ischemia-reperfusion injury. But studies on the methods for protection of the hypertrophied myocardium are rare and controversial. This study was carried out to investigate the effect of rosiglitazone treatment on the isolated reperfused rat hearts made hypertrophy by aortic banding.【Methods】Sprague-Daw1ey rats (aged 6~7 weeks) were subjected either to constriction of the abdominal aorta just above the renal artery or to sham operation. The rats were studied at 6 weeks of age, the hearts were subjected to 2h of global ischemia followed by 1 hour of reperfusion,with the method of rosiglitazone treatment. Animals completing the experiment included the normal age-matched control group(Con-N group, n = 10) ,the untreated group (Con-H, n = 10), rosiglitazone treated group in extracorporeal circulation(Con-N group,n=10), and rosiglitazone pretreated group(Ros-O group, n=10, daily 4mg·kg-1, for 7 days). Recovery of cardiac function, cardiac metabolism and myocardial morphology were assessed.【Results】The left ventricular weight/body weight ratio in the hypertrophied hearts was heigher in the age-matched controls (P<0.01). LVSP measured at 15, 30,60 minutes of reperfusion in group of aortic-constricted rats that were treated or pretreat with rosiglitazone were significantly higher than that of the untreated group (P<0.0l) and LVEDP measured at the same different time points were lower (P<0.0l).Compared with the untreated group,the level of ET,CK,LDH were also reduced (p<0.05 or p<0.01) and the level of NO was significantly increased (p<0.01). Morphometric study of electronmicro graphs demonstrated that mitochondria swelling was distinctlyless in Rosiglitazone-treated than in untreated rats (p<0.01). TENUL test also showed the AI in the Rosiglitazone pretreatment group were lower (p<0.01).【Conclusions】Rosiglitazone treatment and pretreatment in hypertrophied hearts results in significantly improved postischemic recoveries of cardiac function and provides superior protectior of hypertrophied rat hearts. Rosiglitazone reduces or delays the damage to the hypertrophied myocardiac cells. Moreover its effects are maximal in protecting cells from apoptosis, thereby suggesting that mitigating apoptosis may play an important role in rosiglitazone treatment and pretreatment's ability to protect ischemic hypertrophied myocardium.