The Cardioprotective Effect of Brief Acidic Reperfusion after Ischemia in Perfused Rat Hearts is not Mimicked by Inhibition of the Na+/H+ Exchanger NHE1

Cellular Physiology and Biochemistry

关键词: JNK;    p38 MAPK;    Akt/protein kinase B;    Ischemia/reperfusion;    HL-1 cells;    Postconditioning;   

DOI  :  10.1159/000331709

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background Ischemic postconditioning (PostC), i.e. brief ischemia-reperfusion cycles before full reperfusion, is protective against cardiac ischemia/reperfusion (I/R) injury. Inhibition of the Na⁺/H⁺ exchanger NHE1 and delayed intracellular pH-normalization have been proposed to underlie protection by PostC. Methods and Results We used Langendorff perfused rat hearts exposed to 35 min global ischemia to show that 15 min acidic (pH 6.5) treatment at onset of reperfusion decreased infarct size and functional deterioration at least to the same extent as PostC. In contrast, NHE1 inhibition by EIPA was detrimental. To evaluate HL-1 atrial cardiomyocytes as a cellular model for PostC, we exposed the cells to simulated ischemia/reperfusion (I/R) mimicking that in perfused hearts. Necrosis and apoptosis induced by I/R were unaffected by 15 min of pH 6.0 at onset of reperfusion. I/R increased the activity of c-Jun N-terminal Kinase 1/2 (JNK1/2) and Akt, but not of p38 MAPK, with no further effect of acidic reperfusion or EIPA. Conclusion In rat hearts, 15 min acidic reperfusion improves myocardial performance at least as much as does PostC, whereas NHE1 inhibition is detrimental. In contrast, in HL-1 cardiomyocytes, acidic reperfusion or NHE1 inhibition affect neither survival nor JNK1/2-, Akt-, and p38 MAPK activity after I/R, pointing to different mechanisms of damage and protection in these systems.

【 授权许可】

CC BY-NC-ND