Heart Failure, Ischemia Reperfusion Injury, Mitochondrial Pathology
Conditions
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.
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.
Interventions
DIETARY_SUPPLEMENT3-hydroxybuturate
3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model
Sponsors
Aarhus University Hospital
University of Aarhus
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Denmark
Contacts
Primary ContactJacob Seefeldt, B.M
Backup ContactBent Roni Nielsen, M.D., PhD.
Outcome results
None listed