title: Title efficacy of phosphodiesterase 5 inhibitor on distant burn-induced muscle autophagy, microcirculation, and survival rate.
abstract: Skeletal muscle wasting is an exacerbating factor in the prognosis of critically ill patients. Using a systemic burn injury model in mice, we have established a role of autophagy in the resulting muscle wasting that is distant from the burn trauma. We provide evidence that burn injury increases the autophagy turnover in the distal skeletal muscle by conventional postmortem tissue analyses and by a novel in vivo microscopic method using an autophagy reporter gene (tandem fluorescent LC3). The effect of tadalafil, a phosphodiesterase 5 inhibitor (PDE5I), on burn-induced skeletal muscle autophagy is documented and extends our published results that PDE5Is attenuates muscle degeneration in a muscular dystrophy model. We also designed a translational experiment to examine the impact of PDE5I on whole body and demonstrated that PDE5I administration lessened muscle atrophy, mitigated microcirculatory disturbance, and improved the survival rate after burn injury.
authors.affiliation: Department of Anesthesiology and Critical Care and Pain Medicine, Shriners Hospital for Children, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hosokawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Koseki
authors.forename: Michio
authors.initials: M
authors.lastname: Nagashima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maeyama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yomogida
authors.forename: Chelsea
authors.initials: C
authors.lastname: Mehr
authors.forename: Madeleine
authors.initials: M
authors.lastname: Rutledge
authors.forename: Hannah
authors.initials: H
authors.lastname: Greenfeld
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: J A Jeevendra
authors.initials: JA
authors.lastname: Martyn
authors.forename: Shingo E
authors.initials: SE
authors.lastname: Yasuhara
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002056:Burns / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D002243:Carbolines / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D017930:Genes, Reporter; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects*; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D012039:Regional Blood Flow; D013534:Survival; D000068581:Tadalafil; D014945:Wound Healing / Q000187:drug effects
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil; D004247:DNA
keywords: Atg8/LC3; autophagosome turnover and maturation; autophagy; burn injury; in vivo microscopy; muscle wasting; phosphodiesterase 5 inhibitor; sildenafil; skeletal muscle; tadalafil; vardenafil