The Role of Mitochondrial Respiration in the Cardioprotective Capacity of IPC in Diabetic and Non-diabetic Patients

June 6, 2019 updated by: University of Aarhus
The overall aim of this study is to examine the role of mitochondrial respiration in human diabetic tissue before and after ischemia. Furthermore we will examine the ability of ischemic preconditioning (IPC) to preserve the mitochondrial function and hemodynamic performance of both non-diabetic and diabetic fibers after ischemia. To increase our understanding on the metabolic changes during ischemia in both non-diabetic and diabetic tissue we will use Dimethyl Malonate and examine the impact of this blockade on post-ischemic mitochondrial respiration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

20 diabetic and 20 non-diabetic patients undergoing elective CABG surgery or other heart surgery where extracorporal circulation is used will be included in the study. The patiens will not be given any treatment prior to the operation. During the cardiac surgery a small sample of the heart is routinely removed when the patient is connection to the heart-lung machine. From this tissue sample it is possible to isolate muscle trabeculae which will be used in an atrial strip model and randomized to one of four types of treatment. Simultaneously with the isolation of the trabeculae, a fifth trabecular will be used to assess mitochondrial respiration at baseline. Group 1 will serve as a sham control, group 2 will serve as ischemic control and receive an extended period of hypoxia, Group 3 will be treated with ischemic preconditioning, where short periods of non lethal lack of oxygen will be given directly to the tissue (after removal from the patient) prior to the extended period of hypoxia, Group 4 will receive dimethyl malonate prior to the prolonged hypoxia.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Not Applicable

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

18 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients undergoing CABG or other surgery where extracorporal circulation will be used.

Exclusion Criteria:

  • raise in ischemic markers within 4 weeks
  • ejection fraction <30
  • Atrial fibrilation
  • Oral opioid treatment

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: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: non-diabetic Sham control
Heart tissue obtained from non-diabetic patients undergoing surgery will not receive drugs or ischemia
Other: Sham
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
EXPERIMENTAL: non-diabetic Ischemia reperfusion
Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive ischemia
Other: Ischemia reperfusion
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
EXPERIMENTAL: non-diabetic Ischemic preconditioning
Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia
Biological: Ischemic preconditioning
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
EXPERIMENTAL: non-diabetic Dimethyl malonate
Heart tissue from non-diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia
Drug: Dimethyl Malonate
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
Other Names:
  • Dimethyl Malonate; PubChem Substance ID 24848281
EXPERIMENTAL: Diabetic Sham control
Heart tissue obtained from diabetic patients undergoing surgery will not receive drugs or ischemia
Other: Sham
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
EXPERIMENTAL: Diabetic Ischemia reperfusion
Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive ischemia
Other: Ischemia reperfusion
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
EXPERIMENTAL: Diabetic Ischemic preconditioning
Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia
Biological: Ischemic preconditioning
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
EXPERIMENTAL: Diabetic Dimethyl malonate
Heart tissue from diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia
Drug: Dimethyl Malonate
Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
Other Names:
  • Dimethyl Malonate; PubChem Substance ID 24848281

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mitochondrial respiration of individual complexes
Time Frame: Outcome will be assessed within a year when the inclusion of patients is complete
Mitochondrial respiration of individual complexes will serve as primary outcome and will be examined by oxygraph technique.
Outcome will be assessed within a year when the inclusion of patients is complete

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemodynamic performance
Time Frame: Outcome will be assessed within a year when the inclusion of patients is complete
Hemodynamic performance will be measured as contractile force of heart fibers before during and after ischemia.
Outcome will be assessed within a year when the inclusion of patients is complete

Collaborators and Investigators

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

Sponsor

University of Aarhus

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

December 1, 2016

Primary Completion (ACTUAL)

February 1, 2019

Study Completion (ACTUAL)

February 1, 2019

Study Registration Dates

First Submitted

December 8, 2016

First Submitted That Met QC Criteria

December 12, 2016

First Posted (ESTIMATE)

December 15, 2016

Study Record Updates

Last Update Posted (ACTUAL)

June 7, 2019

Last Update Submitted That Met QC Criteria

June 6, 2019

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Human A-strips Mitochondria

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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