Intermittent Normoxia Reduces Myocardial Reperfusion Injury (INCPB)

Effect of Intermittent Normoxic Cardiopulmonary Bypass on Myocardial Reperfusion Injury in Adult Valve Replacement

This study aims to determine the effect of intermittent normoxic cardiopulmonary bypass (CPB) on inflammatory response, oxidative stress and myocardial reperfusion injury in adult patients undergoing valve replacement. The investigators hypothesized that nuclear factor kappa B (NFkB) was involved in regulating gene expression of myocardial inflammatory factor.

Study Overview

• Status: Unknown
• Conditions: Hyperoxia
• Intervention / Treatment: Procedure: intermittent normoxia

Detailed Description

Methods:Patients meeting the requirement will be randomized into 2 groups: the control group received hyperoxic reperfusion (PaO2 180-250 mmHg) throughout CPB as routine; the treatment group underwent 3 cycles of 5/5 min normal/high oxygenation (PaO2 80-150/180-250 mmHg) during cardioplegia arrest, and maintained the same hyperoxia as the control group in the rest time of CPB. The clinical data of inotropes requirement, drainage, ventilation and intensive care time will be recorded. Venous blood samples will be taken perioperatively for detecting concentration of troponin I (cTnI), tumor necrosis factor-α , interleukin-6, 10, and malondialdehyde (MDA). Atrial biopsies will be removed before cardioplegia arrest and 30min after aortic de-clamping to determine the extent of neutrophil infiltration (myeloperoxidase activity), NFkB binding DNA activity, and gene expression of inflammatory factors (TNF-α, IL-6, 10).

Statistical analysis:A sample size of at least 32 patients in each group was needed to have a power of 90%, significance at the two-side 5% level, on the basis that a SD of 0.2 ng/ml and a difference in peak serum cTnI release of about 0.15 ng/ml between control and conditioned patients was determined.

Expected Results: The treatment group will have significantly lower release of cTnI, inflammatory factors, and MDA during CPB and afterwards. Intermittent normoxia may be related to less myocardial inflammation characterized by decreased myeloperoxidase activity, gene expression of inflammatory factors, the later may result from reduced activity of NFkB binding to DNA after reperfusion.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shengxi Chen, M.D.; Phone Number: 86-731-89753413; Email: shengxi.chen@hotmail.com
• Study Contact Backup: Name: Li Li, M.D.; Phone Number: 86-731-84327097; Email: lovelily0920@yahoo.cn

Study Locations

• China
  • Hunan
    • Changsha City, Hunan, China, 410008
      • Recruiting
      • Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University
      • Contact: Wanjun, Luo; Phone Number: 86-731-89753703; Email: luowanjun@yahoo.com
      • Sub-Investigator: Li Li, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• rheumatic heart valve disease requiring selective aortic or double valve(aortic and mitral valve) replacement

Exclusion Criteria:

• infective endocarditis congenital valve disease previous cardiac surgery complicated with diabetes, coronary artery disease, hypertension or peripheral vascular disease.

receiving aspirin, corticosteroids, angiotensin-converting enzyme inhibitors or statin perioperatively

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intermittent normoxia; Repeated brief normoxic reperfusion during cardioplegia arrest in adult valve replacement	Procedure: intermittent normoxia; 3 cycles of 5/5 min normoxia/hyperoxic reperfusion during cardioplegia arrest in adult valve replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
plasma concentration of troponin I	within the first 24h after cardiac surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
gene expression of TNFa, IL-6, and IL-10 in myocardium	30 min after aotic de-clamping

Collaborators and Investigators

• Sponsor: Central South University

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Anticipated): July 1, 2011
• Study Completion (Anticipated): July 1, 2011

Study Registration Dates

• First Submitted: May 3, 2011
• First Submitted That Met QC Criteria: May 5, 2011
• First Posted (Estimate): May 6, 2011

Study Record Updates

• Last Update Posted (Estimate): May 6, 2011
• Last Update Submitted That Met QC Criteria: May 5, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: cardiopulmonary bypass
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Signs and Symptoms, Respiratory; Cardiomyopathies; Reperfusion Injury; Myocardial Reperfusion Injury; Hyperoxia
• Other Study ID Numbers: INCPB