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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model
Aarhus University Hospital
Aarhus, Denmark
Contractile force recovery
Atrial strips model, contractile force (nm\*mm\^-1) during stabilization, ischemia and reperfusion
Time frame: Outcome will be assessed within a year when the inclusion of patients is complete
Mitochondrial respiratory capacity
High Resolution Respirometry, Complex I and Complex I+II respiration (pmol O2 · s-1·mg-1) assessed via a substrate and inhibitor (SUIT) protocol.
Time frame: Outcome will be assessed within a year when the inclusion of patients is complete
Mitochondrial Reactive Oxygen Species production
High Resolution FluoRespirometry, Complex I and Complex I+II linked ROS generation measured with AmplexUltra red and H2O2 interaction fluorescense
Time frame: Outcome will be assessed within a year when the inclusion of patients is complete
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