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  • Title: Inhibition of the Na+/H+ exchanger protects the immature rabbit myocardium from ischemia and reperfusion injury.
    Author: Zhou RH, Long C, Liu J, Liu B.
    Journal: Pediatr Cardiol; 2008 Jan; 29(1):113-20. PubMed ID: 17874219.
    Abstract:
    BACKGROUND: This study investigated the cardioprotective effects of pharmacologic pretreatment with HOE642, a selective Na(+)/H(+ )exchanger (NHE) isoform-1 inhibitor, in immature rabbit hearts, as compared with ischemic preconditioning (IPC). METHODS: For this study, 36 isolated immature New Zealand white rabbit hearts were equilibrated on the Langendorff apparatus. They were randomly divided into three groups: control group, IPC group, and HOE642 group. The hearts in each group were subjected to 60 min of ischemia plus 60 min of reperfusion (I/R). In the IPC group, the hearts were preconditioned by 5 min of ischemia followed by 10 min of reperfusion before I/R. In the HOE642 group, the hearts were pretreated with HOE642 (5 mumol/l) for 15 min before I/R. Left ventricular performance (LVDP, +dp/dt(max), -dp/dt(max)), coronory artery flow (CF), myocardial water content, adenosine triphosphate (ATP), cardiac-specific enzymes (creatine kinase [CK], CK fraction MB [CK-MB], and lacate dehydrogenase [LDH]), and intracellular calcium content were measured. Myocardial ultrastructure was observed under transmission electron microscopy. RESULTS: The recovery rates for left ventricular performance and CF in both the HOE642 and the IPC groups increased compared with those for the control subjects (p < 0.05). Moreover, the recovery rates for LVDP, +dp/dt(max), -dp/dt(max), and CF in the HOE642 group were markedly higher than in the IPC group at most time points of reperfusion (p < 0.05). Compared with the control group, CK, CK-MB, and LDH in the HOE642 group were decreased significantly (p < 0.05), whereas only LDH was reduced in the IPC group (p < 0.05). Water content was significantly reduced and ATP reserve was significantly increased in both the IPC and HOE642 groups (p < 0.05). However, compared with the IPC group, water content in the HOE642 group was significantly lower (81.26% +/- 1.26% vs 83.58% +/- 1.27%; p < 0.05) and ATP was significantly higher (21.46 +/- 2.40 vs 17.66 +/- 1.50 mug/g; p < 0.05). The HOE642 pretreatment exerted a better effect of reducing calcium overload than IPC (265.8 +/- 41.1 vs 408.5 +/- 56.8 mg/kg dry weight; p < 0.05). The blinded ultrastructural assessment under transmission electron microscopy showed that HOE642 brought about more myocyte salvage than IPC. CONCLUSION: This study demonstrated that HOE642 pretreatment is superior to IPC against ischemia and reperfusion injury in isolated immature rabbit myocardium.
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