Molecular hydrogen potentiates beneficial anti-infarct effect of hypoxic postconditioning in isolated rat hearts: Novel cardioprotective intervention

Abstract

Generation of free radicals through incomplete reduction of oxygen during ischemia/ reperfusion is well-described. On the other hand, molecular hydrogen (H2) reduces oxidative stress due to its ability to react with strong oxidants and easily penetrate cells by diffusion, without disturbing metabolic redox reactions. This study was designed to explore cardioprotective potential of hypoxic postconditioning (HpostC) against ischemia/reperfusion (30-min global I/120-min R) in isolated rat hearts using oxygen-free Krebs-Henseleit buffer (KHB). Furthermore, the possibility to potentiate the effect of HpostC by H2 using oxygen-free KHB saturated with H2 (H2+HpostC) was tested. HPostC was induced by 4 cycles of 1-min perfusion with oxygen-free KHB intercepted by 1-min perfusion with normal KHB, at the onset of reperfusion. H2+HPostC was applied in a similar manner using H2 enriched oxygen-free KHB. Cardioprotective effects were evaluated on the basis of infarct size (IS, in % of area at risk, AR) reduction, post-I/R recovery of heart function and occurrence of reperfusion arrhythmias. HPostC significantly reduced IS/AR compared to non-conditioned controls. H2 present in KHB during HPostC further decreased IS/AR compared to the effect of HPostC, attenuated severe arrhythmias, and significantly restored heart function (vs. controls). Cardioprotection by hypoxic postconditioning can be augmented by molecular hydrogen infusion.

Study details

Article type

Original Research

Disease / injury model

Ischemia/reperfusion injury (ex vivo, isolated rat heart)

Dose comparison

Only one concentration of hydrogen (≥0.3 mmol/L) was used; no dose-response comparison was performed.

Dose-dependent effect

No

Outcome

Positive

Findings

Molecular hydrogen, when combined with hypoxic postconditioning, significantly enhances cardioprotection in isolated rat hearts subjected to ischemia/reperfusion injury. This is evidenced by a greater reduction in infarct size, improved recovery of heart function, and decreased severity and incidence of reperfusion-induced arrhythmias compared to hypoxic postconditioning alone or controls.