Abstract
BackgroundHeart transplantation (HTx) is a recognized therapy for terminal heart failure patients; however, it is limited by availability of suitable donors and quality of cardiac grafts. To expand heart donor pool, normothermic ex situ heart perfusion (ESHP) has emerged as a platform for reconditioning marginal donor hearts and consequently increasing the number and quality of organs available for transplant. It also allows continuous functional and metabolic assessment of donor hearts before transplantation. Myocardial function is highly dependent on myocardial perfusion. The coronary autoregulation is essential to maintain normal cardiac function. Our objective is to investigate coronary autoregulation during normothermic ESHP and find ways to protect myocardial function during heart preservation.MethodsThe hearts of anesthetized and intubated domestic breed pigs (N=12) will be harvested after cold cardioplegia arrest. After being mounted on a custom ESHP apparatus, the procured hearts will be perfused ex situ in a beating state in Langendorff mode for 1 hour and then will be switched to working heart system (heart rate=100 beats/minute) to be perfused at 37°C for 12 hours (whole blood based perfusate). Cardiac functional parameters was monitored in the entire interval. Coronary vascular resistance (CVR) was calculated as an indicator of coronary artery function. Myocardial oxygen consumption (MVO2) was determined by coronary blood flow and oxygen extraction as a metabolic parameter. At 1 and 5 hours of perfusion, loading of the heart was varied by increasing or decreasing left atrial pressure to observe the corresponding response in coronary artery flow.ResultsDuring 12 hours normothermic perfusion, cardiac function declined over time as indicated by the cardiac index change at 5 and 11 hours compared with its baseline (p<0.05); myocardial oxygen consumption was decreased significantly (p<0.01, Fig. A). The coronary blood flow increased over time and coronary vascular resistance decreased, with significantly difference at T5 and T11 compared with T1 respectively (p<0.01, Fig. B). At T1 of perfusion, coronary artery flow shows strong correlation with left ventricle stroke work (p<0.01, R2=0.79, Fig. C); however, at T5, the regression line is significantly different (p<0.01), with relative lower slope (R2=0.36, Fig. D), which means as myocardial function demand increases, coronary artery flow increases less proportion than that in T1.ConclusionOur data suggests that regulation of coronary artery function is disturbed during ESHP leading to apparent excessive coronary blood flow over time. This is in contrast to a gradual reduction in myocardial function over time, suggesting that there is loss of coronary autoregulation. The theory of coronary autoregulation states that as myocardial functional demand increases, coronary blood flow increases as well. However, our data reveals a poor correlation between hemodynamics stress and coronary flow suggesting that this autoregulation phenomenon is disturbed. Whether the loss of coronary artery regulation cause the decline of cardiac function or the mechanism of disturbed autoregulation need to be further investigated.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Published Version
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