Effect of hydrogen sulfide on myocardial protection in the setting of cardioplegia and cardiopulmonary bypass.
Interactive cardiovascular and thoracic surgery 2010 Jan 5; In press
Osipov R RM, Robich M, Feng J, Chan V, Clements R RT, Deyo R RJ, Szabo C, Sellke F FW
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
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 (bolusyinfusion, 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). Phospho-endothelial 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 H2S treated groups (P<0.05). The microtubule-associated protein 1 light chain 3 ratio was lower in the infusion group vs. control animals (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. Keywords: Cardiopulmonary bypass; Myocardial protectionyCardioplegia; Cardiac function; Apoptosis.
Keywords: hydrogen sulfide myocardial protection