Remote ischemic preconditioning elaborates a transferable blood-borne effector that protects mitochondrial structure and function and preserves myocardial performance after neonatal cardioplegic arrest

被引:42
作者
Wang, Lixing [2 ]
Oka, Norihiko [2 ]
Tropak, Michael [3 ]
Callahan, John [1 ,3 ]
Lee, John [2 ]
Wilson, Greg [4 ]
Redington, Andrew [2 ]
Caldarone, Christopher A. [1 ,2 ]
机构
[1] Hosp Sick Children, Div Cardiovasc Surg, Toronto, ON M5G 1X8, Canada
[2] Hosp Sick Children, Div Cardiovasc Res, Toronto, ON M5G 1X8, Canada
[3] Hosp Sick Children, Div Genet & Genome Biol, Toronto, ON M5G 1X8, Canada
[4] Hosp Sick Children, Div Pathol, Toronto, ON M5G 1X8, Canada
基金
加拿大健康研究院;
关键词
D O I
10.1016/j.jtcvs.2007.12.055
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Remote ischemic preconditioning is known to elicit production of a blood-home cardioprotective factor that is infarct sparing in models of ischemia-reperfusion injury and myocardial damage reducing after cardiopulmonary bypass in human subjects. The mechanism of protection remains incompletely understood. III this Study, we examined effects on mitochondrial structure and function in a noninfarct model of cardioplegic arrest. Methods: Explanted neonatal rabbit hearts were mounted in a Langendorff preparation and perfused with dialysate of blood taken from sham-treated or remotely preconditioned rabbits. Each heart was subsequently subjected to 1-hour cardioplegic arrest and 30-minute reperfusion periods, during which hemodynamic responses were measured. Mitochondria were isolated for structural and functional measurements. Results: Relative to hearts with sham-treated dialysate, myocardial performance (systolic pressure, maximum positive and negative first derivatives of left ventricular pressure, and left ventricular end-diastolic pressure) was better preserved with dialysate from preconditioned rabbits. Similarly, mitochondria isolated from hearts with dialysate from preconditioned rabbits showed preserved respiration at complex I and IV in the electron transport chain (P <.01 and P <.05, respectively). Mitochondrial outer membrane integrity was also preserved, with diminished sensitivity of mitochondrial respiration to exogenous cytochrome c (P <.01) and less cytosolic diffusion of cytochrome c (P <.01). Mitochondrial resistance to calcium-mediated mitochondrial permeability transition pore opening was not affected. Conclusion: The cardioprotective factor in plasma dialysate after remote preconditioning preserves mitochondrial structure and function in a noninfarct cardioplegic arrest model. This protection is associated with preservation of global myocardial performance.
引用
收藏
页码:335 / 342
页数:8
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