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

University of Aarhus

Status: Completed

Conditions: Reperfusion Injuries, Myocardial

Treatments: Other: Sham; Other: Ischemia reperfusion; Drug: Dimethyl Malonate; Biological: Ischemic preconditioning

Study type: Interventional

Funder types: Other

Identifiers

NCT02993484

Human A-strips Mitochondria

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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39 participants in 8 patient groups

non-diabetic Sham control

Experimental group

Description:

Heart tissue obtained from non-diabetic patients undergoing surgery will not receive drugs or ischemia

Treatment:

Other: Sham

non-diabetic Ischemia reperfusion

Experimental group

Description:

Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive ischemia

Treatment:

Other: Ischemia reperfusion

non-diabetic Ischemic preconditioning

Experimental group

Description:

Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia

Treatment:

Biological: Ischemic preconditioning

non-diabetic Dimethyl malonate

Experimental group

Description:

Heart tissue from non-diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia

Treatment:

Drug: Dimethyl Malonate

Diabetic Sham control

Experimental group

Description:

Heart tissue obtained from diabetic patients undergoing surgery will not receive drugs or ischemia

Treatment:

Other: Sham

Diabetic Ischemia reperfusion

Experimental group

Description:

Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive ischemia

Treatment:

Other: Ischemia reperfusion

Diabetic Ischemic preconditioning

Experimental group

Description:

Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia

Treatment:

Biological: Ischemic preconditioning

Diabetic Dimethyl malonate

Experimental group

Description:

Heart tissue from diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia

Treatment:

Drug: Dimethyl Malonate