The implementation of physiological afterload during ex situ heart perfusion augments prediction of posttransplant function.

Ex situ heart perfusion (ex situ heart perfusion) is an emerging technique that aims to increase the number of organs available for transplantation by augmenting both donor heart preservation and evaluation. Traditionally, ex situ heart perfusion has been performed in an unloaded Langendorff mode, though more recently groups have begun to use pump-supported working mode (PSWM) and passive afterload working mode (PAWM) to enable contractile evaluation during ex situ heart perfusion. To this point, however, neither the predictive effectiveness of the two working modes nor the predictive power of individual contractile parameters has been analyzed. In this article, we use our previously described system to analyze the predictive relevance of a multitude of contractile parameters measured in each working mode. Ten porcine hearts were excised and perfused ex situ in Langendorff mode for 4 h, evaluated using pressure-volume catheterization in both PSWM and PAWM, and transplanted into size-matched recipient pigs. After 3 h, hearts were weaned from cardiopulmonary bypass and evaluated. When correlating posttransplant measurements to their ex situ counterparts, we report that parameters measured in both modes show sufficient power (Spearman rank coefficient > 0.7) in predicting global posttransplant function, characterized by cardiac index and preload recruitable stroke work. For the prediction of specific posttransplant systolic and diastolic function, however, a large discrepancy between the two working modes was observed. With 9 of 10 measured posttransplant parameters showing stronger correlation with counterparts measured in PAWM, it is concluded that PAWM allows for a more detailed and nuanced prediction of posttransplant function than can be made in PSWM.NEW & NOTEWORTHY Ex situ heart perfusion has been proposed as a means to augment the organ donor pool by improving organ preservation and evaluation between donation and transplantation. Using our multimodal perfusion system, we analyzed the impact of using a "passive afterload working mode" for functional evaluation as compared with the more traditional "pump-supported working mode." Our data suggests that passive afterload working mode allows for a more nuanced prediction of posttransplant function in porcine hearts.

A New Multi-Mode Perfusion System for Ex Vivo Heart Perfusion Study.

Ex vivo heart perfusion has been shown to be an effective means of facilitating the resuscitation and assessment of donor hearts for cardiac transplantation. Over the last ten years however, only a few ex vivo perfusion systems have been developed for this application. While results have been promising, a system capable of facilitating multiple perfusion strategies on the same platform has not yet been realized. In this paper, the design, development and testing of a novel and modular ex vivo perfusion system is described. The system is capable of operating in three unique primary modes: the traditional Langendorff Mode, Pump-Supported Working-Mode, and Passive Afterload Working-Mode. In each mode, physiological hemodynamic parameters can be produced by managing perfusion settings. To evaluate heart viability, six experiments were conducted using porcine hearts and measuring several parameters including: pH, aortic pressure, lactate metabolism, coronary vascular resistance (CVR), and myocardial oxygen consumption. Pressure-volume relationship measurements were used to assess left ventricular contractility in each Working Mode. Hemodynamic and metabolic conditions remained stable and consistent across 4 h of ex vivo heart perfusion on the ex vivo perfusion system, validating the system as a viable platform for future development of novel preservation and assessment strategies.

Echocardiographic assessment of left ventricular function in ex situ heart perfusion using pump-supported and passive afterload working mode: a pilot study.

Ex situ heart perfusion (ESHP) has been developed to decrease cold ischemia time and allow metabolic assessment of donor hearts prior to transplantation. Current clinical ESHP systems preserve the heart in an unloaded condition and only evaluate the cardiac metabolic profile. In this pilot study we performed echocardiographic functional assessment using two alternative systems for left ventricular (LV) loading: pump supported afterload working mode (SAM) and passive afterload working modes (PAM). Six hearts were procured from male Yorkshire pigs. During cold ischemia, hearts were mounted on our custom made ESHP circuit and a 3D-printed enclosure for the performance of echocardiography with a standard TEE probe. Following perfusion with Langherdorf mode of the unloaded heart, the system was switched into different working modes to allow LV loading and functional assessment: pump supported (SAM) and passive (PAM). Echocardiographic assessment of left ventricular function in the donor hearts was performed in vivo and at 1 h of ESHP with SAM, after 4.5 h with PAM and after 5.5 h with SAM. We obtained good quality epicardial echocardiographic images at all time points allowing a comprehensive LV systolic assessment. All indices showed a decrease in LV systolic function throughout the trial with the biggest drop after heart harvesting. We demonstrated the feasibility of echocardiographic functional assessment during ESHP and two different working modes. The expected LV systolic dysfunction consisted of a reduction in EF, FAC, FS, and strain throughout the experiment with the most significant decrease after harvesting.

Comparing Donor Heart Assessment Strategies During Ex Situ Heart Perfusion to Better Estimate Posttransplant Cardiac Function.

BACKGROUND: Ex situ heart perfusion (ESHP) limits ischemic periods and enables continuous monitoring of donated hearts; however, a validated assessment method to predict cardiac performance has yet to be established. We compare biventricular contractile and metabolic parameters measured during ESHP to determine the best evaluation strategy to estimate cardiac function following transplantation. METHODS: Donor pigs were assigned to undergo beating-heart donation (n = 9) or donation after circulatory death (n = 8) induced by hypoxia. Hearts were preserved for 4 hours with ESHP while invasive and noninvasive (NI) biventricular contractile, and metabolic assessments were performed. Following transplantation, hearts were evaluated at 3 hours of reperfusion. Spearman correlation was used to determine the relationship between ESHP parameters and posttransplant function. RESULTS: We performed 17 transplants; 14 successfully weaned from bypass (beating-heart donation versus donation after circulatory death; P = 0.580). Left ventricular invasive preload recruitable stroke work (PRSW) (r = 0.770; P = 0.009), NI PRSW (r = 0.730; P = 0.001), and NI maximum elastance (r = 0.706; P = 0.002) strongly correlated with cardiac index (CI) following transplantation. Right ventricular NI PRSW moderately correlated to CI following transplantation (r = 0.688; P = 0.003). Lactate levels were weakly correlated with CI following transplantation (r = -0.495; P = 0.043). None of the echocardiography measurements correlated with cardiac function following transplantation. CONCLUSIONS: Left ventricular functional parameters, especially ventricular work and reserve, provided the best estimation of myocardial performance following transplantation. Furthermore, simple NI estimates of ventricular function proved useful in this setting. Right ventricular and metabolic measurements were limited in their ability to correlate with myocardial recovery. This emphasizes the need for an ESHP platform capable of assessing myocardial contractility and suggests that metabolic parameters alone do not provide a reliable evaluation.

Primed Left Ventricle Heart Perfusion Creates Physiological Aortic Pressure in Porcine Hearts.

This article presents a primed left ventricle heart perfusion method to generate physiologic aortic pressure (AoP) and perform functional assessment. Isolated hearts of male Yorkshire pigs were used to study the hemodynamic behaviors of AoPs generated in the primed left ventricle heart perfusion (n = 6) and conventional (zero-loaded left ventricle) Langendorff perfusion (n = 6). The measurement results show that left ventricular pressure generated in the primed left ventricle heart perfusion is a determinant of physiologic AoP (i.e. systolic and diastolic pressures within physiologic range). The aortic pulse pressure (systolic pressure = 124.5 ± 1.7 mm Hg, diastolic pressure = 87.8 ± 0.9 mm Hg, aortic pulse pressure = 36.7 ± 2.6 mm Hg) from the primed left ventricle heart perfusion represents close match with the in vivo physiologic data. The volume in the left ventricle remains constant throughout the primed left ventricle heart perfusion, which allows us to perform isovolumetric left ventricular pressure measurement in ex vivo heart perfusion (EVHP). Left ventricular contractility measurements (maximum and minimum rates of left ventricular pressure change) were derived for cardiac assessment. In summary, the proposed primed left ventricle heart perfusion method is able to create physiologic AoP and enables left ventricular functional assessment in EVHP in porcine hearts.

The Implementation of an Adjustable Afterload Module for Ex Situ Heart Perfusion.

PURPOSE: Windkessel impedance analysis has proven to be an effective technique for instituting artificial afterload on ex situ hearts. Traditional fixed parameter afterload modules, however, are unable to handle the changing contractile conditions associated with prolonged ex situ heart perfusion. In this paper, an adjustable afterload module is described comprising of three fully adjustable sub-components: a systemic resistor, a proximal resistor and a compliance chamber. METHODS: Using a centrifugal pump, the systemic resistor and compliance chamber were subjected to testing across their operating ranges, whereby the predictability of resistance and compliance values was evaluated. The components were then assembled, and the full module tested on three separate porcine hearts perfused for 6 h with success defined by the ability to maintain physiological systolic and diastolic aortic pressures across flow rate variability. RESULTS: For both the systemic resistor and compliance chamber, experimental measurements agreed with their theoretical equivalents, with coefficients of determination of 0.99 and 0.97 for the systemic resistor and compliance chamber, respectively. During ex situ perfusion, overall 95% confidence intervals demonstrate that physiological systolic (95-96.21 mmHg) and diastolic (26.8-28.8 mmHg) pressures were successfully maintained, despite large variability in aortic flow. Left ventricular contractile parameters, were found to be in line with those in previous studies, suggesting the afterload module has no detrimental impact on functional preservation. CONCLUSIONS: We conclude that due to the demonstrable control of our afterload module, we can maintain physiological aortic pressures in a passive afterload working mode across prolonged perfusion periods, enabling effective perfusion regardless of contractile performance.