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

Reperfusion Injuries, Myocardial Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02993484
• Other study ID #: Human A-strips Mitochondria
• Status: Completed
• Phase: N/A
• Start date: December 2016
• Est. completion date: February 1, 2019

Study information

• Verified date: October 2018
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: February 1, 2019
• Est. primary completion date: February 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Myocardial Reperfusion Injury
• Reperfusion Injuries, Myocardial
• Reperfusion Injury

Intervention

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.

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.

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mitochondrial respiration of individual complexes	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	Hemodynamic performance	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