To gain a comprehensive understanding of the biomechanical behaviour of human heart to explore the concept of myocardial fatigue in response to a temporal range of preload, afterload and drug-induced inotropy using in-vitro contractile assays.
All adult patients between 18 to 85-years old undergoing open-heart surgery who can undergo the consent process for the study
Healthy donor hearts that are deemed non-transplantable and consent received from a legal representative
Patients who do not have the mental capacity to undergo the consent process
For the safety of researchers, patients with evidence of ongoing blood-borne infections such as HIV, or a recent positive test for COVID-19 (within 10 days of last PCR test).
Human cardiac tissues (atrial appendages and ventricular tissue biopsies) are obtained from patients undergoing elective or inpatient open-heart surgery, namely coronary artery bypass grafting and valvular replacement. If available, explanted failing hearts are also recruited for experimentation. A control population consists of healthy donor hearts that are deemed non-transplantable and collected by the Arden Tissue Bank at UHCW.
Cohort
Prospective
In-vitro contractile fatigue protocol
Other interventionUsing contractility assays for muscle slices or the work-loop assay for isolated heart cells, the tissue preparation will undergo a series of contraction and relaxation under varying levels of preload, afterload, stimulation frequency and under other experimental conditions such as drug-induced inotropism.
Changes in the force generated by the muscle cell and/or muscle slice
This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects
Changes in the velocity of shortening by the muscle cell and/or muscle slice
This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects
Changes in the end-systolic force-length relationship of the muscle cell and/or muscle slice
This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects, and calculated by integrating the above force and length changes.
Changes in the phosphorylation potential
This will be calculated by determining the above concentration of adenosine triphosphate and its metabolic by-product including inorganic phosphate, at different times of the contraction fatigue protocol (e.g. before, during, and after).
Changes in the phosphocreatine/ATP ratio
This will be calculated by determining the above concentration of phosphocreatine and ATP at different times of the contraction fatigue protocol (e.g. before, during and after).
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University Hospitals Coventry and Warwickshire NHS Trust
Lead sponsor
Coventry University
Collaborator
