title: Inhaled carbon monoxide provides cerebral cytoprotection in pigs.
abstract: Carbon monoxide (CO) at low concentrations imparts protective effects in numerous preclinical small animal models of brain injury. Evidence of protection in large animal models of cerebral injury, however, has not been tested. Neurologic deficits following open heart surgery are likely related in part to ischemia reperfusion injury that occurs during cardiopulmonary bypass surgery. Using a model of deep hypothermic circulatory arrest (DHCA) in piglets, we evaluated the effects of CO to reduce cerebral injury. DHCA and cardiopulmonary bypass (CPB) induced significant alterations in metabolic demands, including a decrease in the oxygen/glucose index (OGI), an increase in lactate/glucose index (LGI) and a rise in cerebral blood pressure that ultimately resulted in increased cell death in the neocortex and hippocampus that was completely abrogated in piglets preconditioned with a low, safe dose of CO. Moreover CO-treated animals maintained normal, pre-CPB OGI and LGI and corresponding cerebral sinus pressures with no change in systemic hemodynamics or metabolic intermediates. Collectively, our data demonstrate that inhaled CO may be beneficial in preventing cerebral injury resulting from DHCA and offer important therapeutic options in newborns undergoing DHCA for open heart surgery.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America. vmahan@bidmc.harvard.edu
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Mahan
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Leo E
authors.initials: LE
authors.lastname: Otterbein
authors.forename: Frank A
authors.initials: FA
authors.lastname: Pigula
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002248:Carbon Monoxide / Q000008:administration & dosage* / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D019610:Cytoprotection / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D019344:Lactic Acid / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D019344:Lactic Acid; D002248:Carbon Monoxide; D005947:Glucose; D010100:Oxygen