Upregulation of hemeoxygenase enzymes HO-1 and HO-2 following ischemia-reperfusion injury in connection with experimental cardiac arrest and cardiopulmonary resuscitation: Neuroprotective effects of methylene blue
by Wiklund, Lars; Sharma, Aruna; Patnaik, Ranjana; Muresanu, Dafin F.; Sahib, Seaab; Tian, Z. Ryan; Castellani, Rudy J.; Nozari, Ala; Lafuente, José Vicente; Sharma, Hari Shanker
Oxidative stress plays an important role in neuronal injuries after cardiac arrest. Increased production of carbon monoxide (CO) by the enzyme hemeoxygenase (HO) in the brain is induced by the oxidative stress. HO is present in the CNS in two isoforms, namely the inducible HO-1 and the constitutive HO-2. Elevated levels of serum HO-1 occurs in cardiac arrest patients and upregulation of HO-1 in cardiac arrest is seen in the neurons. However, the role of HO-2 in cardiac arrest is not well known. In this review involvement of HO-1 and HO-2 enzymes in the porcine brain following cardiac arrest and resuscitation is discussed based on our own observations. In addition, neuroprotective role of methylene blue- an antioxidant dye on alterations in HO under in cardiac arrest is also presented. The biochemical findings of HO-1 and HO-2 enzymes using ELISA were further confirmed by immunocytochemical approach to localize selective regional alterations in cardiac arrest. Our observations are the first to show that cardiac arrest followed by successful cardiopulmonary resuscitation results in significant alteration in cerebral concentrations of HO-1 and HO-2 levels indicating a prominent role of CO in brain pathology andmethylene blue during CPR followed by induced hypothermia leading to superior neuroprotection after return of spontaneous circulation (ROSC), not reported earlier.