title: Nitric oxide release by deoxymyoglobin nitrite reduction during cardiac ischemia: A mathematical model.
abstract: Interactions between cardiac myoglobin (Mb), nitrite, and nitric oxide (NO) are vital in regulating O2storage, transport, and NO homeostasis. Production of NO through the reduction of endogenous myocardial nitrite by deoxygenated myoglobin has been shown to significantly reduce myocardial infarction damage and ischemic injury. We developed a mathematical model for a cardiac arteriole and surrounding myocardium to examine the hypothesis that myoglobin switches functions from being a strong NO scavenger to an NO producer via the deoxymyoglobin nitrite reductase pathway. Our results predict that under ischemic conditions of flow, blood oxygen level, and tissue pH, deoxyMb nitrite reduction significantly elevates tissue and smooth muscle cell NO. The size of the effect is consistent at different flow rates, increases with decreasing blood oxygen and tissue pH and, in extreme pathophysiological conditions, NO can even be elevated above the normoxic levels. Our simulations suggest that cardiac deoxyMb nitrite reduction is a plausible mechanism for preserving or enhancing NO levels using endogenous nitrite despite the rate-limiting O2levels for endothelial NO production. This NO could then be responsible for mitigating deleterious effects under ischemic conditions.
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
authors.forename: Yien
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Buerk
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Barbee
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA. Electronic address: dov.jaron@drexel.edu.
authors.forename: Dov
authors.initials: D
authors.lastname: Jaron
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D001783:Blood Flow Velocity; D015687:Cell Hypoxia; D003198:Computer Simulation; D003326:Coronary Circulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D009716:Numerical Analysis, Computer-Assisted; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D012039:Regional Blood Flow
chemical_list: D009211:Myoglobin; D009573:Nitrites; C055547:deoxymyoglobin; D009569:Nitric Oxide; D010100:Oxygen
keywords: Arteriole model; Mass transport; Myocardial infarction; Myoglobin nitrite reductase