Hydrogen sulfide preconditioning shows differential protection towards interfibrillar and subsarcolemmal mitochondria from isolated rat heart subjected to revascularization injury.

BACKGROUND: Hydrogen sulfide (H2S) is well known to protect the heart from ischemia reperfusion injury by specifically modulating the mitochondrial adenosine-triphosphate-linked potassium channel, thereby preserving mitochondrial function. The present study is designed to investigate the H2S preconditioning effect specifically on the mitochondrial subpopulation, namely, interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria.

METHODS: Isolated heart perfusion model with the method of Langendorff was used to induce reperfusion injury in rat hearts. The animals were randomly divided into five groups: normal, ischemia (ISC), reperfusion (IR), preconditioning (IPC), and H2S preconditioning (HIPC). All the groups, except normal and ischemia, were subjected to 30-min global ischemia followed by 60-min reperfusion with Krebs-Henseleit buffer.

RESULTS: Our study results show that H2S at a dose of 20 μM significantly (P<.05) reduced the infarct size (59%) and the creatine kinase and lactate dehydrogenase activity in cardiac tissue. DNA fragmentation as observed in ischemia reperfusion control was absent in case of H2S-preconditioned heart. On comparing the classical protection provided by IPC with H2S, a significant recovery was seen in the IFM fraction in case of HIPC, whereas the SSM could not recover as evidenced by better mitochondrial respiration rate and electron chain enzyme activities. Studies on isolated mitochondrial subpopulation from normal, IR, and IPC hearts exposed to H2S in vitro support the above observation.

CONCLUSION: The present study concluded that IFM shows major contribution towards H2S-mediated cardioprotection, whereas classical IPC recovered both subpopulations from IR injury.