Experimental Study About Protective Effect Of Trimetazidine Pretreatment On Hypertrophied Myocardium In Rat

【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 trimetazidine pretreatment on the isolated reperfused rat hearts made hypertrophy by aortic banding.【Methods】Sprague-Daw1ey rats (aged 8weeds) were subjected either to constriction of the abdominal aorta just above the renal artery or to sham operation. The rats were studied at 14 weeks of age, the hearts were subjected to 2h of global ischemia followed by 1 hour of reperfusion,with trimetazidine pretreatment (daily 30mg/kg, for 7 days) or unpretreatment. Animals completing the experiment included the trimetazidine pretreated group(n=10), the unpretreated group (n=10), and normal age-matched control group(n=10). Recovery of cardiac function, cardiac metabolism and myocardial morphology were assessed.【Results】The left ventricular weight/body weight ratio in the hypertrophied hearts was 4.57±0.06(g/kg) versus 3.16±0.07(g/kg) 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 with trimetazidine 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 unpretreated group,the level of MDA of heart in the trimetazidine pretreatment group were lower (p<0.05 or p<0.01),the level of ET,CK,LDH were also reduced (p<0.05 or p<0.01) and the level of NO,SOD were significantly increased (p<0.01). Morphometric study of electronmicro graphs demonstrated that mitochondria swelling was distinctlyless in trimetazidine-treated than in untreated rats (p<0.01). TENUL test also showed the AI in the trimetazidine pretreatment group were lower (p<0.05).【Conclusions】Trimetazidine pretreatment in hypertrophied hearts results in significantly improved postischemic recoveries of cardiac function and provides superior protectior of hypertrophied rat hearts. Trimetazidine reduces or delays the damage to the hypetrophied myocardiac cells. Moreover its effects are maximal in protecting the mitochondria, thereby suggesting that mitochondrial salvage may play an important role in trimetazidine pretreatment's ability to protect ischemic hypertrophied myocardium.