Abstract 17695: Transsulfuration Pathway is Essential for Fasting-Induced Cardioprotection Against Ischemic/Reperfusion Injury

: Hydrogen sulfide (H 2 S), a gaseous mediator that is endogenously produced by two transsulfuration enzymes, cystathionine β-synthase (CBS) and cystathionine gamma-lyase (CTH), is known to act against myocardial ischemia/reperfusion (I/R) injury. However, the roles of the transsulfuration that is also essential for cysteine/glutathione biosynthesis remain to be clarified. We investigated the role of transsulfuration pathway in myocardial I/R injury and fasting-induced cardioprotection using mice lacking CBS (CBS -/- ) or CTH (CTH -/- ). : Ad libitum (AL) fed wild-type mice (Wt), CBS -/- and CTH -/- displayed no alteration in basal cardiac functions when evaluated by echocardiography. The Langendorff experiment, in which isolated perfused hearts were subjected to 25-min global ischemia followed by 60-min reperfusion, revealed a similar degree of I/R injury among AL-fed 3 strains. However, “2-day-fasting” induced much better LV functional recovery after I/R in Wt but not in CBS -/- and CTH -/- ( Figure ). Fasting failed to reduce total LDH release into the perfusate even in Wt. In Wt, fasting upregulated CBS mRNA expression in the heart. Heart glutathione contents were comparable indistinguishable between Wt and CTH -/- in either AL - fed or fasting condition. : These results demonstrate that fasting attenuates myocardial stunning (reversible change) but not myocardial infarction (irreversible damage) and strongly suggest the involvement of H 2 S generated by CBS / CTH in fasting-induced cardioprotection. Further investigation is required to assess the role of homocysteinemia on fasting-induced cardioprotection since both CBS -/- and CTH -/- exhibit hyperhomocysteinemia.