HO-1 and Muscle Mitochondrial Dysfunction in Sepsis

Overview

The current project was designed to examine dynamic changes in muscle wasting during sepsis. Researchers will focus the mitochondrial dysfunction of muscle cells and investigate the role of HO-1 in it. Researchers interested in identifying factors involved in the pathology of muscle wasting during sepsis.

Full Title of Study: “Skeletal Muscle Wasting in Patients With Sepsis”

Study Type

• Study Type: Observational
• Study Design
  • Time Perspective: Prospective
• Study Primary Completion Date: June 2016

Detailed Description

Rapid muscle atrophy or muscle wasting occured to septic patients.Sepsis induced muscle wasting has become a severe, frequent, and persistent complication among critically ill patients. Multiple factors including ubiquitin-proteasome system, proinflammatory cytokines and oxidative stress contribute muscle proteolysis. It is known that heme oxygenase-1 (HO-1) possesses a variety of functions like anti-inflammatory, antioxidative and anti-apoptosis effects. In order to investigate the mechanisms under the condition, researchers are going to examine the role of HO-1 in muscle atrophy during sepsis.

Interventions

• Procedure: therapy according to SSC guidelines and muscle biopsy
  • Septic patients will be treated according to the international guidelines for management of severe sepsis and septic shock 2012. Skeletal muscle biopsies, blotted free from blood, are frozen within 30 seconds in liquid nitrogen, and stored in liquid nitrogen until processing.150-300 mg muscle (wet weight) was routinely obtained , which is more than sufficient for the analyses proposed, with some muscle remaining for any additional validation assays that may arise during the course of the research. Muscle will be processed either for isolation of mRNA/microRNA or protein
• Procedure: standard surgery for femoral fracture and muscle biopsy
  • Patients with femoral fracture will under standard surgery for fracture fixation. Percutaneous needle muscle biopsies will be performed. Skeletal muscle biopsies, blotted free from blood, are frozen within 30 seconds in liquid nitrogen, and stored in liquid nitrogen until processing.150-300 mg muscle (wet weight) was routinely obtained , which is more than sufficient for the analyses proposed, with some muscle remaining for any additional validation assays that may arise during the course of the research. Muscle will be processed either for isolation of mRNA/microRNA or protein

Arms, Groups and Cohorts

• sepsis
  • Patients with a diagnosis of sepsis or severe sepsis,immobilization for 3 days at least. Therapy according to the SSC guidelines will be applied. therapy according to SSC guidelines and muscle biopsy
• Patients with femoral fractures
  • non septic patients with a femoral fracture,who need an fixation surgery.standard surgery for femoral fracture and muscle biopsy will be performed.

Clinical Trial Outcome Measures

Primary Measures

• HO-1 mRNA and protein expression, mitochondria function of musculus vastus lateralis
  • Time Frame: 3 days after diagnosis

Secondary Measures

• length of ICU stay
  • Time Frame: 60 days
• length of mechanical ventilation
  • Time Frame: 60 days
• muscle myosin content
  • Time Frame: 3 days after diagnosis

Participating in This Clinical Trial

Inclusion Criteria

• sepsis, severe sepsis, septic shock – clinical reason for fixation surgery of femoral fractures Exclusion Criteria:

• no informed consent – medical history of myopathy – unintended weight loss before surgery or ICU admission – chronic use of corticosteroids

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Changhai Hospital
• Provider of Information About this Clinical Study
  • Principal Investigator: Xiaoming Deng, Chief, Professer – Changhai Hospital
• Overall Official(s)
  • Xiaoming Deng, M.D., Ph.D., Principal Investigator, Changhai Hospital