Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure
Study Details
Study Description
Brief Summary
This proof of concept study aims to evaluate the effects of applying ketone bodies to human atrial tissue biopsies using an atrial strips model and high resolution respirometry.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Ketone bodies are high energy molecules which are naturally occurring in the body during fasting or stress.
Recently, ketone bodies have been shown to improve cardiac function in patients with heart failure(1) through a mechanism, which has yet to be elaborated.
We wish to evaluate the effects of ketone body administration on cardiac tissue subjected to ischemia reperfusion injury. We will evaluate contractile force of the and the mitochondrial performance. Cardiac atrial tissue will be obtained from patients undergoing coronary artery bypass grafting (CABG) or valve replacement surgery. Patients will be recruited after signing an informed consent and allocated in heart failure / non-heart failure groups based on a clinical evaluation.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Heart failure Ejection fraction < 45% |
Dietary Supplement: 3-hydroxybuturate
3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model
|
| Other: Non-heart failure Ejection fraction > 45% |
Dietary Supplement: 3-hydroxybuturate
3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model
|
Outcome Measures
Primary Outcome Measures
- Contractile force recovery [Outcome will be assessed within a year when the inclusion of patients is complete]
Atrial strips model, contractile force (nm*mm^-1) during stabilization, ischemia and reperfusion
Secondary Outcome Measures
- Mitochondrial respiratory capacity [Outcome will be assessed within a year when the inclusion of patients is complete]
High Resolution Respirometry, Complex I and Complex I+II respiration (pmol O2 · s-1·mg-1) assessed via a substrate and inhibitor (SUIT) protocol.
- Mitochondrial Reactive Oxygen Species production [Outcome will be assessed within a year when the inclusion of patients is complete]
High Resolution FluoRespirometry, Complex I and Complex I+II linked ROS generation measured with AmplexUltra red and H2O2 interaction fluorescense
Eligibility Criteria
Criteria
Inclusion Criteria:
- EF < / > 45%, hospitalized for elective CABG or heart valve surgery
Exclusion Criteria:
- Myocardial infarction within 4 weeks, atrial fibrillation, medically treated thyroid disease, oral treatment with opioids.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aarhus University Hospital | Aarhus | Denmark | 8200 |
Sponsors and Collaborators
- University of Aarhus
- Aarhus University Hospital
Investigators
- Study Director: Hans Erik Bøtker, M.D., Prof., Aarhus University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- KetoCard01