Myocardial preconditioning reduces kidney injury and apoptosis induced by myocardial ischaemia and reperfusion

OBJECTIVES: Acute kidney injury is a common and serious complication of cardiac surgery. Because its underlying mechanisms are unclear, there is no specific therapy to prevent or treat it. A regional transient ischaemia and reperfusion (I/R) may provide protection to distant tissue or organs, a phenomenon known as remote preconditioning. In this study, we investigated whether myocardial preconditioning (MPC) would reduce kidney injury and apoptosis induced by myocardial I/R, as well as the mechanisms involved. METHODS: Myocardial I/R was induced by a 40-min occlusion of the left anterior descending artery and a 3-h reperfusion in anaesthetized Sprague-Dawley rats. MPC was elicited by two 10-min coronary artery occlusions and two 10-min reperfusions. A sham group received the same surgical procedures without coronary artery occlusion and reperfusion. RESULTS: Compared with the sham group, myocardial I/R significantly increased the serum creatinine levels (1.15 +/- 0.44 vs 0.54 +/- 0.23 mg/dl, P < 0.05, mean +/- standard deviation) and renal histological damage, indicating increased kidney injury. Kidney apoptosis was also significantly increased, as evidenced by the increase in the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labelling (TUNEL)-positive nuclei, clear DNA laddering and increased caspase-3 activation. Serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6) were significantly elevated, as were TNF-alpha levels in the kidneys. MPC significantly decreased myocardial infarct size (18.5 +/- 3.1 vs 25.6 +/- 2.1% of area at risk, P < 0.001). Additionally, MPC significantly reduced the serum creatinine level (0.65 +/- 0.19 mg/dl, P < 0.05), renal histological damage and apoptosis. The increase in the serum levels of TNF-a, IL-1 and IL-6, and of TNF-alpha in the kidneys, was significantly inhibited. Western blot analysis found that MPC significantly increased Bcl-2 and decreased Bax in the kidneys. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2) was significantly increased. Haemodynamics, area at risk and mortality did not differ significantly among the groups. CONCLUSIONS: MPC significantly reduces kidney injury and apoptosis induced by myocardial I/R. The underlying mechanisms might be related to inhibition of both the extrinsic and intrinsic pathways of apoptosis, possibly via inhibition of TNF-alpha production, modulation of Bcl-2 and Bax and activation of Akt and ERK1/2.