Title efficacy of phosphodiesterase 5 inhibitor on distant burn-induced muscle autophagy, microcirculation, and survival rate

被引：27

作者：

Hosokawa, Sachiko ^{[1
,2
]}

Koseki, Hiroaki ^{[1
,2
]}

Nagashima, Michio ^{[1
,2
]}

Maeyama, Yoshihiro ^{[1
,2
]}

Yomogida, Kentaro ^{[1
,2
]}

Mehr, Chelsea ^{[1
,2
]}

Rutledge, Madeleine ^{[1
,2
]}

Greenfeld, Hannah ^{[1
,2
]}

Kaneki, Masao ^{[1
,2
]}

Tompkins, Ronald G. ^{[1
,2
]}

Martyn, J. A. Jeevendra ^{[1
,2
]}

Yasuhara, Shingo E. ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesiol & Crit Care & Pain Med, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2013年 / 304卷 / 09期

关键词：

muscle wasting; burn injury; phosphodiesterase; 5; inhibitor; sildenafil; tadalafil; vardenafil; autophagy; skeletal muscle; in vivo microscopy; Atg8/LC3; autophagosome turnover and maturation; NITRIC-OXIDE; MUSCULAR-DYSTROPHY; OXIDATIVE STRESS; CRITICAL ILLNESS; RELAXING FACTOR; INJURY; SILDENAFIL; APOPTOSIS; PROTEIN; MICROSCOPY;

D O I：

10.1152/ajpendo.00078.2013

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：E922 / E933

页数：12

共 52 条

[1] NITRIC-OXIDE ACTIVATES GUANYLATE CYCLASE AND INCREASES GUANOSINE 3'-5'-CYCLIC MONOPHOSPHATE LEVELS IN VARIOUS TISSUE PREPARATIONS [J].