Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure

Study Overview
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Brief Summary
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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
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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.

Official Title
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Functional and Metabolic Effects of Ketone Bodies on Human Atrial Tissue in Patients With and Without Heart Failure

Conditions
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Heart Failure, Ischemia Reperfusion Injury, Mitochondrial Pathology

Intervention / Treatment
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* Dietary Supplement: 3-hydroxybuturate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Heart failure<br>Ejection fraction < 45% | Dietary Supplement: 3-hydroxybuturate<br>* 3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model<br>|
| Other: Non-heart failure<br>Ejection fraction > 45% | Dietary Supplement: 3-hydroxybuturate<br>* 3-hydroxybuturate will be administered directly as a modified Krebs Henseleit buffer in a super perfused atrial strips model<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contractile force recovery | Atrial strips model, contractile force (nm*mm^-1) during stabilization, ischemia and reperfusion | Outcome will be assessed within a year when the inclusion of patients is complete | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | Outcome will be assessed within a year when the inclusion of patients is complete |