title: Creatine and creatine pyruvate reduce hypoxia-induced effects on phrenic nerve activity in the juvenile mouse respiratory system.
abstract: Adequate concentrations of ATP are required to preserve physiological cell functions and protect tissue from hypoxic damage. Decreased oxygen concentration results in ATP synthesis relying increasingly on the presence of phosphocreatine. The lack of ATP through hypoxic insult to neurons that generate or regulate respiratory function, would lead to the cessation of breathing (apnea). It is not clear whether creatine plays a role in maintaining respiratory phrenic nerve (PN) activity during hypoxic challenge. The aim of the study was to test the effects of exogenously applied creatine or creatine pyruvate in maintaining PN induced respiratory rhythm against the deleterious effects of severe hypoxic insult using Working Heart-Brainstem (WHB) preparations of juvenile Swiss type mice. WHB's were perfused with control perfusate or perfusate containing either creatine [100μM] or creatine pyruvate [100μM] prior to hypoxic challenge and PN activity recorded throughout. Results showed that severe hypoxic challenge resulted in an initial transient increase in PN activity, followed by a reduction in that activity leading to respiratory apnea. The results demonstrated that perfusing the WHB preparation with creatine or creatine pyruvate, significantly reduced the onset of apnea compared to control conditions, with creatine pyruvate being the more effective substance. Overall, creatine and creatine pyruvate each produced time-dependent degrees of protection against severe hypoxic-induced disturbances of PN activity. The underlying protective mechanisms are unknown and need further investigations.
authors.affiliation: Onkologie, Hämatologie, Immunologie, Klinikum Stuttgart Olgahospital, Stuttgart, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Scheer
authors.affiliation: Georg-August-Universität Göttingen, Abteilung für Neuro- und Sinnesphysiologie, Göttingen, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bischoff
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic. Electronic address: kruzliakpeter@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Opatrilova
authors.affiliation: Weill Cornell Medicine in Qatar, Qatar Foundation-Education City, Doha, Qatar.
authors.forename: Douglas
authors.initials: D
authors.lastname: Bovell
authors.affiliation: Weill Cornell Medicine in Qatar, Qatar Foundation-Education City, Doha, Qatar. Electronic address: dib2015@qatar-med.cornell.edu.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Büsselberg
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D003401:Creatine / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D009043:Motor Activity; D010791:Phrenic Nerve / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism*; D012137:Respiratory System / Q000294:innervation* / Q000378:metabolism*
chemical_list: D019289:Pyruvic Acid; D003401:Creatine
keywords: Creatine; Creatine pyruvate; Hypoxia; Working heart-brainstem preparation