Effect of hydrogen sulfide on myocardial protection in the setting of cardioplegia and cardiopulmonary bypass

We investigated the impact of hydrogen sulfide (H₂S) on myocardium in the setting of cold crystalloid cardioplegia and cardiopulmonary bypass (CP/CPB). Eighteen male Yorkshire pigs underwent 1 h CP/CPB followed by 2 h of reperfusion. Pigs received either: placebo (control, n=9), or H₂S (as NaHS) as a bolusyinfusion (bolus/infusion, n=6), or as an infusion (infusion, n=6). The expression pattern of various myocardial effector pathways was investigated. Coronary microvascular relaxation to endothelium-dependent and -independent agonists was assessed. No differences in cardiac function were observed among groups. Endothelium-dependent microvascular relaxation to adenosine diphosphate was improved in the H₂S bolusyinfusion group only (P<0.05). The expression of hemeoxygenase-1, phospho-heat shock proteins27 and phospho-p44/42 MAPK extracellular signal-regulated kinase were higher in H₂S-treated groups (P<0.05). Phosphoendothelial nitric oxide synthase (P=0.08), phospho-B-cell lymphoma 2 (P=0.09), and phospho-Bad (P=0.06) all displayed a trend to be higher with H₂S treatment. The expressions of apoptosis inducing factor and Bcl 2/adenovirus E1B 19 kDa-interacting protein were lower in HS treated groups (P<0.05). The microtubule-associated protein 1 light chain 3 ratio was lower in the infusion group vs. control animals 2 (P<0.05). There was a trend for lower phospho-mammalian target of rapamycin expression in the infusion group (P=0.07), whereas phosphorylation of p70S6K1 was higher with H₂S-treatment (P=0.09). This study demonstrates that H₂S-treatment may offer biochemical myocardial protection via attenuation of caspase-independent apoptosis and autophagy in the setting of CP/CPB.