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

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

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

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.

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.

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

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

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

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

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

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

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

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.

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.

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.

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.

Mitochondrial respiration of individual complexes will serve as primary outcome and will be examined by oxygraph technique.

Hemodynamic performance will be measured as contractile force of heart fibers before during and after ischemia.

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