Cardioprotection Of Fructose1,6-diphosphate On Ischemia/Reperfusion Injury In Isolated Rat Hearts

Objective: The study is to investigate the cardioprotection of postconditioning withfructose1,6-diphosphate on ischemia/reperfusion injury in isolated rat hearts, and toprovide theoretical basis for clinical therapy to myocardial ischemia/reperfusion injury.Methods:Preparation of isolated rat heart global isehemia/reperfusion model usesLengendorff Isolated Heart Perfusion System.Thirty-two Sprague-Dawley rats arerandomly divided into four groups (8each):ischemia/reperfusion group (I/R group),ischemia preconditioning group (IPC group), fructose1,6-diphosphate preconditioninggroup (FPC group) and fructose1,6-diphosphate postconditioning group (FPOgroup).All hearts experienced30min index ischemia followed by60min reperfusion.Three cycles of low-flow ischemia for3min followed by full-flow reperfusin for3minwere applied before index ischemia in IPC group. K-H liquid with fructose1,6-diphosphate was perfused for15min before index ischemia in FPC group. K-H liquidwith fructose1,6-diphosphate was perfused for15min at the beginning of reperfusionwhile it without fructose1,6-diphosphate was perfused for45min at resedual reperfusionin FPO group. Left ventricular developed pressure (LVDP), maximal rate of leftventricular pressure of development(＋dp/dtmax), Left ventricular end-diastolic pressure(LVEDP), maximal rate of left ventricular pressure of decline (－dp/dtmax), heart rate(HR),coronary flow (CF), Left ventricular systolic pressure (LVSP) and Left ventriculardiastolic pressure (LVDP#) were recorded at30min of equilibration(T0),30min ofischemia(T1), and5min(T2),15min(T3),30min(T4),60min(T5) of reperfusion, and(LVSP LVDP#)×HR were caiculated at each timepoint. At the end of the experiment, Superoxide dismutase (SOD) and Malondialdehyde (MDA) in myocardium tissue aredetected by colorimetry. Myocardial fixed paraffin-embedded tissue sections areperformed apoptosis index by TUNEL and immunohistochemical method are used todetecte Bcl-2and Bax.Results:1.Compared with T0,LVDP,±dp/dtmax, HR, and (LVSP-LVDP#)*HR in eachgroup declined significantly at T1(P＜0.01),while LVEDP elevated significantly at T1(P＜0.01). Compared with T0,LVDP,±dp/dtmax, HR, and (LVSP-LVDP#)*HR in group I/Rdroped significantly at T3～5(P＜0.05or P＜0.01), while its LVEDP rised significantly atT2～5(P＜0.05or P＜0.01). Compared with T0,LVDP,±dp/dtmax, HR,(LVSP-LVDP#)*HRand CF in group IPC decreased significantly at parts of timepionts from T2to T5(P＜0.05),while its LVEDP increased significantly at T2～5(P＜0.05). Compared with T0,LVDP,±dp/dtmax, HR, and (LVSP-LVDP#)*HR in group FPC and FPO had no significantstatistical differences at T2～5(P＞0.05), while LVEDP had no significant statisticaldifferences at T3～5(P＞0.05). Compared with group I/R, LVDP, LVEDP,±dp/dtmax, HR,(LVSP-LVDP#)*HR and CF in group IPC had no significant statistical differences(P＞0.05). Compared with group I/R, LVDP,±dp/dtmax, HR,(LVSP-LVDP#)*HR and CF ingroup FPC and FPO elevated significantly at T3～5(P＜0.05or P＜0.01), while LVEDP ingroup FPC and FPO descended significantly at T3～5(P＜0.05or P＜0.01).2.Comparedwith group I/R, the rise of SOD and the decline of MDA in group IPC had no significantstatistical differences (P＞0.05). Compared with group I/R, SOD in group FPC and FPOincreased significantly (P＜0.05), while MDA in group FPC and FPO decreasedsignificantly (P＜0.05).3. Compared with group I/R, the expression of Bcl-2and Bax ingroup IPC had no significant statistical differences (P＞0.05). Compared with group I/R,the expression of Bcl-2in group FPC and FPO augmented significantly (P＜0.05), whilethe expression of Bax in group FPC and FPO lessened significantly (P＜0.05). Comparedwith group I/R, AI in group IPC had no significant statistical differences (P＞0.05), whileit in group FPC and FPO reduced significantly (P＜0.05). Conclusion:1.Postconditioning with fructose1,6-diphosphate can evidently increaseintracellular energy production of cardiomyocytes and improve isolated cardiac functionin rats suffered ischemia/reperfusion.2.Postconditioning, as preconditioning, withfructose1,6-diphosphate can protect cardiomyocytes in isolated rat heart which sufferedischemia/reperfusion.