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Liming Xin - One of the best experts on this subject based on the ideXlab platform.
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Model Reference Adaptive Control for Aortic Pressure Regulation in Ex Vivo Heart Perfusion
IEEE Transactions on Control Systems Technology, 2021Co-Authors: Liming Xin, Mitesh V. Badiwala, Weiran Yao, Yan Peng, Shaorong Xie, Yu SunAbstract:This brief proposes the first model reference adaptive control (MRAC) method for aortic pressure (AoP) regulation and maintaining the Heart’s physiological aerobic metabolism in ex vivo Heart Perfusion (EVHP). A mathematical model of the EVHP was established to describe the hemodynamic behavior of EVHP and quantify the changes in cardiac parameters. A reference model consisting of a virtual proportional–integral–derivative (PID) controller and the EVHP model was employed to generate the reference trajectory of AoP. An adaptation algorithm tunes the control parameters based on the reference model and the isolated Heart. Experiments were conducted using large animal Hearts (50 ± 5 kg porcine) to validate the adaptive controller’s performance for stepwise and fast switching AoP references. The results confirmed the effectiveness of the proposed controller for regulating the AoP in isolated porcine Hearts, in an accurate (mean error less than 2 mmHg) and fast (4–8 s of settling time) manner.
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Comparing Donor Heart Assessment Strategies During Ex Situ Heart Perfusion to Better Estimate Post-Transplant Cardiac Function.
Transplantation, 2020Co-Authors: Roberto Vanin Pinto Ribeiro, Liming Xin, Bryan Gellner, Mitchell B. Adamson, Emanuela Paradiso, Arnaud Romeo Mbadjeu Hondjeu, J. Alvarez, Maja Degen, Ved BissoondathAbstract: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.
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primed left ventricle Heart Perfusion creates physiological aortic pressure in porcine Hearts
Asaio Journal, 2020Co-Authors: Liming Xin, Bryan Gellner, Roberto Vanin Pinto Ribeiro, Weiran Yao, Yan Peng, Bin Wei, Craig A SimmonsAbstract: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.
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The Implementation of an Adjustable Afterload Module for Ex Situ Heart Perfusion.
Cardiovascular engineering and technology, 2019Co-Authors: Bryan Gellner, Liming Xin, Roberto Vanin Pinto Ribeiro, Ved Bissoondath, Mitchell B. Adamson, Emanuela Paradiso, Craig A SimmonsAbstract: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.
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The implementation of physiological afterload during ex situ Heart Perfusion augments prediction of posttransplant function.
American journal of physiology. Heart and circulatory physiology, 2019Co-Authors: Bryan Gellner, Liming Xin, Roberto Vanin Pinto Ribeiro, Ved Bissoondath, Mitchell B. Adamson, Emanuela Paradiso, Arnaud Romeo Mbadjeu Hondjeu, Craig A SimmonsAbstract: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 perfus...
Roberto Vanin Pinto Ribeiro - One of the best experts on this subject based on the ideXlab platform.
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Comparing Donor Heart Assessment Strategies During Ex Situ Heart Perfusion to Better Estimate Post-Transplant Cardiac Function.
Transplantation, 2020Co-Authors: Roberto Vanin Pinto Ribeiro, Liming Xin, Bryan Gellner, Mitchell B. Adamson, Emanuela Paradiso, Arnaud Romeo Mbadjeu Hondjeu, J. Alvarez, Maja Degen, Ved BissoondathAbstract: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.
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primed left ventricle Heart Perfusion creates physiological aortic pressure in porcine Hearts
Asaio Journal, 2020Co-Authors: Liming Xin, Bryan Gellner, Roberto Vanin Pinto Ribeiro, Weiran Yao, Yan Peng, Bin Wei, Craig A SimmonsAbstract: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.
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Comparison of Lactate and Glucose during Ex Situ Heart Perfusion as Predictors of Early-Stage Heart Transplantation Outcomes
The Journal of Heart and Lung Transplantation, 2020Co-Authors: L. Xin, Roberto Vanin Pinto Ribeiro, Weiran Yao, Yan Peng, Yu Sun, J. Alvarez, Mitesh V. BadiwalaAbstract:Purpose Ex situ Heart Perfusion (ESHP) provides a means to assess Heart viability prior to transplantation. Lactate concentration has been used to predict post-transplant viability. However, many studies show that lactate is insufficient for marginal Hearts or Heart donated after circulatory death (DCD) evaluation. We sought to determine if glucose is a better indicator to predict early-stage Heart transplantation outcomes than lactate. Methods We utilized a custom-developed ESHP system to analyze and compare the predictive relevance of the lactate and glucose measured in ESHP. Six donations after brain death (DBD) and seven DCD pig Hearts were excised and perfused ex situ in Langendorff mode for four hours according to the current experimental protocol of our program. D5W was infused continuously at the rate of 25ml/h. Arterial and venous lactate and glucose were measured at T1 and T4. Hearts were then transplanted into recipient pigs. After three hours, Hearts were weaned from cardiopulmonary bypass and cardiac index (CI) was measured. Results Post-transplant CI (CI was set to zero if pig died or failed to wean) was correlated to the ex situ lactate and glucose data. As shown in Fig. 1, arterial glucose and glucose trend (glucoseT4 - GlucoseT1) at T4 shows sufficient power (r= 0.7035 and r= 0.6834, respectively) in predicting early post-transplant outcome; glucose shows much better predictive performance in DCD Heart group(Fig 1ef lactate at T4 shows lower correlation with post-transplant CI (r= 0.5594), while lactate trend (LactateT4 - LactateT1) has limited ability to predict post-transplant outcome (r= 0.2323). Conclusion Glucose concentration demonstrates a better capability to predict early transplant outcomes than lactate in the porcine model.
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The Implementation of an Adjustable Afterload Module for Ex Situ Heart Perfusion.
Cardiovascular engineering and technology, 2019Co-Authors: Bryan Gellner, Liming Xin, Roberto Vanin Pinto Ribeiro, Ved Bissoondath, Mitchell B. Adamson, Emanuela Paradiso, Craig A SimmonsAbstract: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.
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The implementation of physiological afterload during ex situ Heart Perfusion augments prediction of posttransplant function.
American journal of physiology. Heart and circulatory physiology, 2019Co-Authors: Bryan Gellner, Liming Xin, Roberto Vanin Pinto Ribeiro, Ved Bissoondath, Mitchell B. Adamson, Emanuela Paradiso, Arnaud Romeo Mbadjeu Hondjeu, Craig A SimmonsAbstract: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 perfus...
Christopher W. White - One of the best experts on this subject based on the ideXlab platform.
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The Position of the Heart During Normothermic Ex Situ Heart Perfusion is an Important Factor in Preservation and Recovery of Myocardial Function.
ASAIO journal (American Society for Artificial Internal Organs : 1992), 2021Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Consolato Sergi, Sabin J. Bozso, David S. Nobes, Hyun-joong Chung, Darren H. FreedAbstract:Ex situ Heart Perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated Heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the Heart and may negatively affect the functional preservation of the Heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig Hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position Hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode Perfusion in supported position = 94.77% versus nonworking mode Perfusion in supported position = 62.80%, working mode Perfusion in H position = 36.18%, nonworking mode Perfusion in H position = 9.75%; p < 0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H Heart groups. The Hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H Hearts in non-S position. Optimizing the positional support for the ex situ-perfused Hearts may improve myocardial preservation during ESHP.
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Immunity and Stress Responses Are Induced During Ex Situ Heart Perfusion.
Circulation. Heart failure, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Martin Ondrus, Alexandra Kinnear, Sayed Himmat, Jayan Nagendran, Max T. Buchko, Consolato Sergi, Darren H. FreedAbstract:Background: Ex situ Heart Perfusion (ESHP) preserves the donated Heart in a perfused, beating condition preventing cold storage–related ischemia and provides a platform to evaluate myocardial viabi...
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Preservation and Recovery of Myocardial Function during Normothermic Ex Situ Heart Perfusion: Does the Position of the Heart during Perfusion Matter?
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Max T. Buchko, S. Bozsu, Darren H. FreedAbstract:Purpose Ex-situ Heart Perfusion preserves the donated Heart in a perfused and semi-physiologic condition preventing preservation-related ischemia however, myocardial function declines overtime in this setting. All models of ex-situ Heart Perfusion (ESHP) position the Heart in a suspended state which is at considerable variance with the in vivo positioning of the Heart. In vivo, the aorta, vasculature and extracellular matrix support the myocardial mass. We hypothesize that the suspended myocardium may sustain greater injury and therefore may have greater decline in function compared to the supported myocardium. Methods In this study, cardiac function and metabolism was assessed in healthy pig Hearts, perfused for 12 hours, in either a conventional suspended position (susp) in which the Heart is perfused suspending from the main vascular cannulas, or in a supported position (supp) in which the Heart is perfused lying on a supporting membrane with integrated vascular cannulas (Figure 1). The Hearts in each position were perfused either in non-working mode (NWM) or working mode (WM). Results Cardiac function was best preserved in the Hearts perfused in a supported position in WM (relative 11-hour cardiac index / 1-hour cardiac index %: WM-supp=94.25 vs. NWM-supp=54.85, WM-susp=37.43, NWM-sup=11.17, p Conclusion ESHP in a semi-anatomical supported position, and physiologic, WM leads to less tissue injury and better preservation of myocardial function and viability.
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The Impact of Whole Blood versus Dilute Whole Blood on Coronary Vascular Tone during Ex Situ Heart Perfusion
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Max T. Buchko, Sabin J. Bozso, Larissa Lautner, X. Wang, Darren H. FreedAbstract:Purpose Ex situ Heart Perfusion (ESHP) allows continuous functional and metabolic assessment of donor Hearts before transplantation. Evidence indicates that circulating chemical mediators in whole blood are involved in the regulation of oxygen delivery. We aim to evaluate the impact of whole blood versus dilute whole blood in the regulation of coronary vascular tone during ESHP. Methods Normal porcine Hearts were perfused in working mode for 6 hours either by whole blood (n=5) or whole blood with Krebs-Henseleit solution (1:1) containing 8% albumin (n=5). Cardiac functional parameters, coronary artery flow and metabolism were monitored continuously. Coronary vascular resistance (CVR) was calculated to evaluate coronary artery function. These parameters were compared between groups at different time. Results The whole blood group had significantly higher hemoglobin concentration than blood+buffer group (p Conclusion Whole blood appears to play a role in regulating coronary vascular tone, as indicated by relative higher vascular resistance and better oxygen delivery in whole blood Perfusion after 6 hours. The relative contribution of hemoglobin content versus plasma protein content is not clear. Whether this translates into improved post-transplant function remains to be determined.
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Myocardial Functional Decline During Prolonged Ex Situ Heart Perfusion.
The Annals of thoracic surgery, 2019Co-Authors: Sanaz Hatami, Christopher W. White, Shubham Shan, Alois Haromy, Martin Ondrus, Alexandra Kinnear, Sayed Himmat, Evangelos D. Michelakis, Jayan NagendranAbstract:Background Myocardial function declines in a time-dependent fashion during ex situ Heart Perfusion. Cell death and metabolic alterations may contribute to this phenomenon, limiting the safe Perfusion period and the potential of ex situ Heart Perfusion to expand the donor pool. Our aim was to investigate the etiology of myocardial functional decline in ex situ perfused Hearts. Methods Cardiac function, apoptosis, effectors and markers of cell death, and metabolic function were assessed in healthy pig Hearts perfused for 12 hours. These Hearts were perfused in nonworking mode or working mode. Results Cardiac function declined during ex situ Heart Perfusion regardless of Perfusion mode but was significantly better preserved in the Hearts perfused in working mode (11-hour cardiac index/1-hour cardiac index: working mode, 33%; nonworking mode, 10%; p = 0.025). The rate of apoptosis was higher in the ex situ perfused Hearts compared with in vivo samples (apoptotic cells: in vivo, 0.13%; working mode, 0.54%; nonworking mode, 0.88%; p Conclusions A significant decline in myocardial function occurs over time in Hearts preserved ex situ that is out of proportion to the magnitude of myocyte cell death present in dysfunctional Hearts. Alterations in myocardial substrate utilization during prolonged ex situ Heart Perfusion may contribute to this phenomenon and represent an avenue to improve donor Heart preservation.
Sanaz Hatami - One of the best experts on this subject based on the ideXlab platform.
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The Position of the Heart During Normothermic Ex Situ Heart Perfusion is an Important Factor in Preservation and Recovery of Myocardial Function.
ASAIO journal (American Society for Artificial Internal Organs : 1992), 2021Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Consolato Sergi, Sabin J. Bozso, David S. Nobes, Hyun-joong Chung, Darren H. FreedAbstract:Ex situ Heart Perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated Heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the Heart and may negatively affect the functional preservation of the Heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig Hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position Hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode Perfusion in supported position = 94.77% versus nonworking mode Perfusion in supported position = 62.80%, working mode Perfusion in H position = 36.18%, nonworking mode Perfusion in H position = 9.75%; p < 0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H Heart groups. The Hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H Hearts in non-S position. Optimizing the positional support for the ex situ-perfused Hearts may improve myocardial preservation during ESHP.
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Immunity and Stress Responses Are Induced During Ex Situ Heart Perfusion.
Circulation. Heart failure, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Martin Ondrus, Alexandra Kinnear, Sayed Himmat, Jayan Nagendran, Max T. Buchko, Consolato Sergi, Darren H. FreedAbstract:Background: Ex situ Heart Perfusion (ESHP) preserves the donated Heart in a perfused, beating condition preventing cold storage–related ischemia and provides a platform to evaluate myocardial viabi...
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Preservation and Recovery of Myocardial Function during Normothermic Ex Situ Heart Perfusion: Does the Position of the Heart during Perfusion Matter?
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Max T. Buchko, S. Bozsu, Darren H. FreedAbstract:Purpose Ex-situ Heart Perfusion preserves the donated Heart in a perfused and semi-physiologic condition preventing preservation-related ischemia however, myocardial function declines overtime in this setting. All models of ex-situ Heart Perfusion (ESHP) position the Heart in a suspended state which is at considerable variance with the in vivo positioning of the Heart. In vivo, the aorta, vasculature and extracellular matrix support the myocardial mass. We hypothesize that the suspended myocardium may sustain greater injury and therefore may have greater decline in function compared to the supported myocardium. Methods In this study, cardiac function and metabolism was assessed in healthy pig Hearts, perfused for 12 hours, in either a conventional suspended position (susp) in which the Heart is perfused suspending from the main vascular cannulas, or in a supported position (supp) in which the Heart is perfused lying on a supporting membrane with integrated vascular cannulas (Figure 1). The Hearts in each position were perfused either in non-working mode (NWM) or working mode (WM). Results Cardiac function was best preserved in the Hearts perfused in a supported position in WM (relative 11-hour cardiac index / 1-hour cardiac index %: WM-supp=94.25 vs. NWM-supp=54.85, WM-susp=37.43, NWM-sup=11.17, p Conclusion ESHP in a semi-anatomical supported position, and physiologic, WM leads to less tissue injury and better preservation of myocardial function and viability.
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The Impact of Whole Blood versus Dilute Whole Blood on Coronary Vascular Tone during Ex Situ Heart Perfusion
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Max T. Buchko, Sabin J. Bozso, Larissa Lautner, X. Wang, Darren H. FreedAbstract:Purpose Ex situ Heart Perfusion (ESHP) allows continuous functional and metabolic assessment of donor Hearts before transplantation. Evidence indicates that circulating chemical mediators in whole blood are involved in the regulation of oxygen delivery. We aim to evaluate the impact of whole blood versus dilute whole blood in the regulation of coronary vascular tone during ESHP. Methods Normal porcine Hearts were perfused in working mode for 6 hours either by whole blood (n=5) or whole blood with Krebs-Henseleit solution (1:1) containing 8% albumin (n=5). Cardiac functional parameters, coronary artery flow and metabolism were monitored continuously. Coronary vascular resistance (CVR) was calculated to evaluate coronary artery function. These parameters were compared between groups at different time. Results The whole blood group had significantly higher hemoglobin concentration than blood+buffer group (p Conclusion Whole blood appears to play a role in regulating coronary vascular tone, as indicated by relative higher vascular resistance and better oxygen delivery in whole blood Perfusion after 6 hours. The relative contribution of hemoglobin content versus plasma protein content is not clear. Whether this translates into improved post-transplant function remains to be determined.
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Myocardial Functional Decline During Prolonged Ex Situ Heart Perfusion.
The Annals of thoracic surgery, 2019Co-Authors: Sanaz Hatami, Christopher W. White, Shubham Shan, Alois Haromy, Martin Ondrus, Alexandra Kinnear, Sayed Himmat, Evangelos D. Michelakis, Jayan NagendranAbstract:Background Myocardial function declines in a time-dependent fashion during ex situ Heart Perfusion. Cell death and metabolic alterations may contribute to this phenomenon, limiting the safe Perfusion period and the potential of ex situ Heart Perfusion to expand the donor pool. Our aim was to investigate the etiology of myocardial functional decline in ex situ perfused Hearts. Methods Cardiac function, apoptosis, effectors and markers of cell death, and metabolic function were assessed in healthy pig Hearts perfused for 12 hours. These Hearts were perfused in nonworking mode or working mode. Results Cardiac function declined during ex situ Heart Perfusion regardless of Perfusion mode but was significantly better preserved in the Hearts perfused in working mode (11-hour cardiac index/1-hour cardiac index: working mode, 33%; nonworking mode, 10%; p = 0.025). The rate of apoptosis was higher in the ex situ perfused Hearts compared with in vivo samples (apoptotic cells: in vivo, 0.13%; working mode, 0.54%; nonworking mode, 0.88%; p Conclusions A significant decline in myocardial function occurs over time in Hearts preserved ex situ that is out of proportion to the magnitude of myocyte cell death present in dysfunctional Hearts. Alterations in myocardial substrate utilization during prolonged ex situ Heart Perfusion may contribute to this phenomenon and represent an avenue to improve donor Heart preservation.
Darren H. Freed - One of the best experts on this subject based on the ideXlab platform.
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The Position of the Heart During Normothermic Ex Situ Heart Perfusion is an Important Factor in Preservation and Recovery of Myocardial Function.
ASAIO journal (American Society for Artificial Internal Organs : 1992), 2021Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Consolato Sergi, Sabin J. Bozso, David S. Nobes, Hyun-joong Chung, Darren H. FreedAbstract:Ex situ Heart Perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated Heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the Heart and may negatively affect the functional preservation of the Heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig Hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position Hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode Perfusion in supported position = 94.77% versus nonworking mode Perfusion in supported position = 62.80%, working mode Perfusion in H position = 36.18%, nonworking mode Perfusion in H position = 9.75%; p < 0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H Heart groups. The Hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H Hearts in non-S position. Optimizing the positional support for the ex situ-perfused Hearts may improve myocardial preservation during ESHP.
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Immunity and Stress Responses Are Induced During Ex Situ Heart Perfusion.
Circulation. Heart failure, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Martin Ondrus, Alexandra Kinnear, Sayed Himmat, Jayan Nagendran, Max T. Buchko, Consolato Sergi, Darren H. FreedAbstract:Background: Ex situ Heart Perfusion (ESHP) preserves the donated Heart in a perfused, beating condition preventing cold storage–related ischemia and provides a platform to evaluate myocardial viabi...
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Preservation and Recovery of Myocardial Function during Normothermic Ex Situ Heart Perfusion: Does the Position of the Heart during Perfusion Matter?
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Max T. Buchko, S. Bozsu, Darren H. FreedAbstract:Purpose Ex-situ Heart Perfusion preserves the donated Heart in a perfused and semi-physiologic condition preventing preservation-related ischemia however, myocardial function declines overtime in this setting. All models of ex-situ Heart Perfusion (ESHP) position the Heart in a suspended state which is at considerable variance with the in vivo positioning of the Heart. In vivo, the aorta, vasculature and extracellular matrix support the myocardial mass. We hypothesize that the suspended myocardium may sustain greater injury and therefore may have greater decline in function compared to the supported myocardium. Methods In this study, cardiac function and metabolism was assessed in healthy pig Hearts, perfused for 12 hours, in either a conventional suspended position (susp) in which the Heart is perfused suspending from the main vascular cannulas, or in a supported position (supp) in which the Heart is perfused lying on a supporting membrane with integrated vascular cannulas (Figure 1). The Hearts in each position were perfused either in non-working mode (NWM) or working mode (WM). Results Cardiac function was best preserved in the Hearts perfused in a supported position in WM (relative 11-hour cardiac index / 1-hour cardiac index %: WM-supp=94.25 vs. NWM-supp=54.85, WM-susp=37.43, NWM-sup=11.17, p Conclusion ESHP in a semi-anatomical supported position, and physiologic, WM leads to less tissue injury and better preservation of myocardial function and viability.
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The Impact of Whole Blood versus Dilute Whole Blood on Coronary Vascular Tone during Ex Situ Heart Perfusion
The Journal of Heart and Lung Transplantation, 2020Co-Authors: Sanaz Hatami, Christopher W. White, Sayed Himmat, Jayan Nagendran, Max T. Buchko, Sabin J. Bozso, Larissa Lautner, X. Wang, Darren H. FreedAbstract:Purpose Ex situ Heart Perfusion (ESHP) allows continuous functional and metabolic assessment of donor Hearts before transplantation. Evidence indicates that circulating chemical mediators in whole blood are involved in the regulation of oxygen delivery. We aim to evaluate the impact of whole blood versus dilute whole blood in the regulation of coronary vascular tone during ESHP. Methods Normal porcine Hearts were perfused in working mode for 6 hours either by whole blood (n=5) or whole blood with Krebs-Henseleit solution (1:1) containing 8% albumin (n=5). Cardiac functional parameters, coronary artery flow and metabolism were monitored continuously. Coronary vascular resistance (CVR) was calculated to evaluate coronary artery function. These parameters were compared between groups at different time. Results The whole blood group had significantly higher hemoglobin concentration than blood+buffer group (p Conclusion Whole blood appears to play a role in regulating coronary vascular tone, as indicated by relative higher vascular resistance and better oxygen delivery in whole blood Perfusion after 6 hours. The relative contribution of hemoglobin content versus plasma protein content is not clear. Whether this translates into improved post-transplant function remains to be determined.
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Mimicking "J-Shaped" and Anisotropic Stress-Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites.
ACS applied materials & interfaces, 2019Co-Authors: Dinara Zhalmuratova, Darren H. Freed, David S. Nobes, Alexander R. A. Szojka, Stephen H. J. Andrews, Adetola B. Adesida, Chun Il Kim, Hyun-joong ChungAbstract:An ex vivo Heart Perfusion device preserves the donor Heart in a warm beating state during transfer between extraction and implantation surgeries. One of the current challenges includes the use of ...
