Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism

Hatami, Sanaz; White, Christopher W.; Ondrus, Martin; Xiao, Qi; Buchko, Max; Himmat, Sayed; Lin, Lily; Cameron, Katie; Nobes, David S.; Chung, Hyun‐Joong; Nagendran, Jayan; Freed, Darren H.

doi:10.3791/58430

Cited by 11 publications

(15 citation statements)

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“…The stress–strain curves of the human and porcine aortas are compared at a maximum strain of 150%, although a previous study has shown that the average physiological strain in the circumferential direction of healthy human aortas is approximately 32%, while the maximum is 57% . The physiological pressure range of the aorta is from 30 to 120 mmHg, , which corresponds to an average wall stress of 120–200 kPa. , For this study, the stress values were compared to the failure of aortas. When comparing these two samples, the human aorta was stiffer than the porcine aorta.…”

Section: Resultsmentioning

confidence: 99%

Mimicking “J-Shaped” and Anisotropic Stress–Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites

Zhalmuratova¹,

La²,

Yu³

et al. 2019

ACS Appl. Mater. Interfaces

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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 rigid and noncompliant plastic tubes, which causes injuries to the heart at the junction between the tissue and the tube. The compliant and rapidly strain-stiffening mechanical property that generates a “J-shaped” stress–strain behavior is necessary for producing the Windkessel effect, which ensures continuous flow of blood through the aorta. In this study, we mimic the J-shaped and anisotropic stress–strain behavior of human aorta in synthetic elastomers to replace the problematic noncompliant plastic tube. First, we assess the mechanical properties of human (n = 1) and porcine aorta (n = 14) to quantify the nonlinear and anisotropic behavior under uniaxial tensile stress from five different regions of the aorta. Second, fabric-reinforced elastomer composites were prepared by reinforcing silicone elastomers with embedded fabrics in a trilayer geometry. The knitted structures of the fabric provide strain-stiffening as well as anisotropic mechanical properties of the resulting composite in a deterministic manner. By optimizing the combination between different elastomers and fabrics, the resulting composites matched the J-shaped and anisotropic stress–strain behavior of natural human and porcine aorta. Finally, improved analytical constitutive models based on Gent’s and Mooney–Rivlin’s constitutive model (to describe the elastomer matrix) combined with Holzapfel–Gasser–Ogden’s model (to represent the stiffer fabrics) were developed to describe the J-shaped behavior of the natural aortas and the fabric-reinforced composites. We anticipate that the suggested fabric-reinforced silicone elastomer composite design concept can be used to develop complex soft biomaterials, as well as in emerging engineering fields such as soft robotics and microfluidics, where the Windkessel effect can be useful in regulating the flow of fluids.

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Section: Resultsmentioning

confidence: 99%

Mimicking “J-Shaped” and Anisotropic Stress–Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites

Zhalmuratova¹,

La²,

Yu³

et al. 2019

ACS Appl. Mater. Interfaces

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“…However, there are obvious differences between those, including exclusive, isolated perfusion of the procured organ in ESOP as opposed to systemic perfusion in ECLS, or lesser bloodair interface in ECMO (closed circuit) compared to CPB. The similarities and differences of ESHP with ECLS systems are summarized in Table 1 (4,5,19,20).…”

Section: Similarities and Differences Between Ecls And Esop Settings ...mentioning

confidence: 99%

“…Later, with addition of RBC to the perfusate to reach a hematocrit of 35%, the oxygen delivery of the perfusate to the heart improved with more physiologic values of PaO 2 (122). More recently, in the experimental studies using a RBC-containing perfusate (either whole blood or separated RBCs), the PaO 2 is maintained mostly in the range of 100≤PaO2<200 mmHg, which is able to provide a physiological oxygen saturation (20,123,124). Interestingly, in ESLP, while most common approach in ESLP has been using a deoxygenated perfusate containing 6% oxygen, In a rat model of ESLP and lung transplantation, Noda et al demonstrated that the perfusate containing 40% or 60% oxygen, when compared to 6%, or 100%, showed significantly lower inflammation expression of the inflammatory cytokine genes in the lung tissue during ESLP, while the group with 40% oxygen in perfusate showed the best post-transplantation pulmonary function (125).…”

Section: Hyperoxiamentioning

confidence: 99%

“…In ESOP, when compared to standard donor organ preservation method (i.e., SCS), the duration of cold ischemia is considerably shorter. However, ischemia still occurs with the hypoperfusion period following the withdrawal of the life support in the donor, during procurement of the organ, and during mounting of the organ on the ex-situ perfusion apparatus (20). More over, in case of DCD, longer warm ischemic times are expected due to the mandatory "no touch" period that is required to confirm the irreversible loss of circulatory function before organ procurement proceeds.…”

Section: Ischemia-reperfusion Injurymentioning

confidence: 99%

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Inflammation and Oxidative Stress in the Context of Extracorporeal Cardiac and Pulmonary Support

2022

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Extracorporeal circulation (ECC) systems, including cardiopulmonary bypass, and extracorporeal membrane oxygenation have been an irreplaceable part of the cardiothoracic surgeries, and treatment of critically ill patients with respiratory and/or cardiac failure for more than half a century. During the recent decades, the concept of extracorporeal circulation has been extended to isolated machine perfusion of the donor organ including thoracic organs (ex-situ organ perfusion, ESOP) as a method for dynamic, semi-physiologic preservation, and potential improvement of the donor organs. The extracorporeal life support systems (ECLS) have been lifesaving and facilitating complex cardiothoracic surgeries, and the ESOP technology has the potential to increase the number of the transplantable donor organs, and to improve the outcomes of transplantation. However, these artificial circulation systems in general have been associated with activation of the inflammatory and oxidative stress responses in patients and/or in the exposed tissues and organs. The activation of these responses can negatively affect patient outcomes in ECLS, and may as well jeopardize the reliability of the organ viability assessment, and the outcomes of thoracic organ preservation and transplantation in ESOP. Both ECLS and ESOP consist of artificial circuit materials and components, which play a key role in the induction of these responses. However, while ECLS can lead to systemic inflammatory and oxidative stress responses negatively affecting various organs/systems of the body, in ESOP, the absence of the organs that play an important role in oxidant scavenging/antioxidative replenishment of the body, such as liver, may make the perfused organ more susceptible to inflammation and oxidative stress during extracorporeal circulation. In the present manuscript, we will review the activation of the inflammatory and oxidative stress responses during ECLP and ESOP, mechanisms involved, clinical implications, and the interventions for attenuating these responses in ECC.

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“…1 These donors typically include older individuals, those with previous conditions, and donors with circulatory (DCD), as opposed to brain (DBD), determined death. 2,3 The potential risks of using extended criteria hearts have motivated the study of non-beating, 4,5 empty beating, 6 and working heart models [7][8][9][10] to perfuse the cardiac muscles and provide indicators of heart performance prior to transplantation.…”

Section: Introductionmentioning

confidence: 99%

A novel nonlinear afterload for ex vivo heart evaluation: Porcine experimental results

et al. 2022

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Background Existing working heart models for ex vivo functional evaluation of donor hearts often use cardiac afterloads made up of discrete resistive and compliant elements. This approach limits the practicality of independently controlling systolic and diastolic aortic pressure to safely test the heart under multiple loading conditions. We present and investigate a novel afterload concept designed to enable such control. Methods Six ∼70 kg pig hearts were evaluated in vivo, then ex vivo in left‐ventricular working mode using the presented afterload. Both in vivo and ex vivo, the hearts were evaluated at two exertion levels: at rest and following a 20 μg adrenaline bolus, while measuring aortic pressure and flow, left ventricular pressure and volume, and left atrial pressure. Results The afterload gave aortic pressure waveforms that matched the general shape of the in vivo measurements. A wide range of physiological systolic pressures (93 to 160 mm Hg) and diastolic pressures (73 to 113 mm Hg) were generated by the afterload. Conclusions With the presented afterload concept, multiple physiological loading conditions could be tested ex vivo, and compared with the corresponding in vivo data. An additional control loop from the set pressure limits to the measured systolic and diastolic aortic pressure is proposed to address discrepancies observed between the set limits and the measured pressures.

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Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism

Cited by 11 publications

References 0 publications

Mimicking “J-Shaped” and Anisotropic Stress–Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites

Mimicking “J-Shaped” and Anisotropic Stress–Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites

Inflammation and Oxidative Stress in the Context of Extracorporeal Cardiac and Pulmonary Support

A novel nonlinear afterload for ex vivo heart evaluation: Porcine experimental results

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