Mitochondrial Apoptotic Pathway Induced by Myocardial Ischemia-Reperfusion Injury in Human

April 29, 2015 updated by: WANG Yan-bin

Background: The cardiomyocytes apoptosis induced by ischemia-reperfusion(I/R) is one of the most important factors in the myocardial I/R injury(MIRI) undergoing cardiac valve replacement with cardiopulmonary bypass(CVRCPB),and Ischemic postconditioning (I-postC) can inhibit apoptosis of myocardial cells. Consequently, this study investigated the key genes and apoptosis signaling pathways of myocardium in patients undergoing CVRCPB.

Methods: A total of 36 New York Heart Association class II or III patients with rheumatic heart disease (RHD) of both sexes, aged 21-59 years, who were scheduled for first cardiac valve replacement with CPB in the investigators' hospital from February 2014 to May 2015, were randomly divided into the following three groups (n=12 each): negative control group (NEG group); I/R group (POS group); and I-postC group (Treat group). In the Treat group, the procedure involved 5 min before opening the ascending aorta, aortic unclamping for 30 s, and cross-clamping for 30 s for three cycles, after which the ascending aorta was completely opened. The NEG and Treat groups were not treated. Thirty-six patients were assessed for arrhythmia and recovery of myocardial contractile function after reperfusion by electrocardiograms and degree of dependence on vasoactive drugs. The myocardial tissues of the right atrial appendage were obtained at 3 min before CPB was established in the NEG group, and at 45 min after opening the aorta in the POS and Treat groups. In all three groups, the myocardial tissues of the right atrial appendage were obtained and preserved at -80°C for further experiments. The right atrial appendage of three patients randomly selected in each group was fixed with RNA later (Qiagen, Hilden, Germany) in a centrifuge tube overnight at 4°C, and then preserved at -20°C for RNA extraction. Human 12×135K Gene Array profiling of mRNA expressions was undertaken in human cardiac muscle cells. Differentially expressed mRNAs verified by quantitative real-time RT-PCR were subjected to pathway analysis. The mRNA expressions of AIF, APAF1, CYCS, Bax, caspase-3, caspase-9, caspase-6, caspase-7, BCL2, BAG1, and PI3K were assessed by real-time RT-PCR and western blot analysis. The levels of myocardial apoptosis induced by I/R were investigated by TUNEL assays. The changes in MIRI induced by myocardial apoptosis were investigated by pathologic examination of the myocardium.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Shenzhen, China
        • Recruiting
        • Shenzhen Sun Yat-sen Cardiovascular Hospital
        • Contact:
          • Yanbin Wang, Master of Medicine
          • Phone Number: +8615816886696
          • Email: wangyb666@126.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 59 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • New York Heart Association class II or III
  • aged 21-59 years
  • scheduled for first cardiac valve replacement with CPB

Exclusion Criteria:

  • The patient with a history of heart operation or diabetes,
  • with a history of liver and/or kidney dysfunction,
  • with a history of coronary heart disease and the left ventricular ejection fraction(LVEF)<0.4, receiving drugs with pretreatment effectssuchas hormones, ATP-sensitive potassium (KATP) channel openers,insulin,et al. within preoperative one week,

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: negative control group
The myocardial tissues of the right atrial appendage were obtained at 3 min before CPB was established in the NEG group.
Active Comparator: I/R group
The myocardial tissues of the right atrial appendage were obtained at 45 min after opening the aorta in the I/R group.
In the Treat group, the procedure involved 5 min before opening the ascending aorta, aortic unclamping for 30 s, and cross-clamping for 30 s for three cycles, after which the ascending aorta was completely opened.
Other Names:
  • The intervention is neither a drug nor a device. It is a procedure.
Experimental: I-postC group
The procedure involved 5 min before opening the ascending aorta, aortic unclamping for 30 s, and cross-clamping for 30 s for three cycles, after which the ascending aorta was completely opened.
In the Treat group, the procedure involved 5 min before opening the ascending aorta, aortic unclamping for 30 s, and cross-clamping for 30 s for three cycles, after which the ascending aorta was completely opened.
Other Names:
  • The intervention is neither a drug nor a device. It is a procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
recovery of myocardial contractile function after reperfusion
Time Frame: 1 day
1 day
degree of dependence on vasoactive drugs
Time Frame: 1 day
1 day
number of participants with postoperative arrhythmia
Time Frame: 1 day
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (Anticipated)

May 1, 2015

Study Registration Dates

First Submitted

April 20, 2015

First Submitted That Met QC Criteria

April 29, 2015

First Posted (Estimate)

April 30, 2015

Study Record Updates

Last Update Posted (Estimate)

April 30, 2015

Last Update Submitted That Met QC Criteria

April 29, 2015

Last Verified

April 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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