Current preservation technology and future prospects of thoracic organs. Part 2: heart

Jacobs, Steven; Rega, Filip; Meyns, Bart

doi:10.1097/mot.0b013e328337343f

Cited by 32 publications

(24 citation statements)

References 46 publications

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“…However, there is evidence to suggest that hypothermia inhibits sodium-potassium ATPase activity during the reperfusion of ischemic myocardium (17). Most enzymatic processes have a 1.5-2.5-fold decrease in enzyme activity rate for every 108C decrease in temperature (35), and profound hypothermia has been shown to decrease the efficiency of oxidative phosphorylation and limit the synthesis of ATP (36). Taken together, these studies suggest that initial reperfusion with a profoundly hypothermic cardioplegia is likely to inhibit sodium-potassium ATPase activity and the generation of ATP required for the restoration of ionic homeostasis (17).…”

Section: Discussionmentioning

confidence: 99%

Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death

White

Ambrose

Müller

et al. 2016

American Journal of Transplantation

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The resuscitation of hearts donated after circulatory death (DCD) is gaining widespread interest; however, the method of initial reperfusion (IR) that optimizes functional recovery has not been elucidated. We sought to determine the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-min standoff period was observed and then hearts were reperfused for 3 min at three different temperatures (58C; N ¼ 6, 258C; N ¼ 5, and 358C; N ¼ 7) with a normokalemic adenosine-lidocaine crystalloid cardioplegia. Hearts then underwent normothermic EVHP for 6 h during which time myocardial function was assessed in a working mode. We found that IR coronary blood flow differed among treatment groups (58C ¼ 483 AE 53, 258C ¼ 722 AE 60, 358C ¼ 906 AE 36 mL/ min, p < 0.01). During subsequent EVHP, less myocardial injury (troponin I: 58C ¼ 91 AE 6, 258C ¼ 64 AE 16, 358C ¼ 57 AE 7 pg/mL/g, p ¼ 0.04) and greater preservation of endothelial cell integrity (electron microscopy injury score: 58C ¼ 3.2 AE 0.5, 258C ¼ 1.8 AE 0.2, 358C ¼ 1.7 AE 0.3, p ¼ 0.01) were evident in hearts initially reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of myocardial function (cardiac index: 58C ¼ 3.9 AE 0.8, 258C ¼ 6.2 AE 0.4, 358C ¼ 6.5 AE 0.6 mL/minute/g, p ¼ 0.03) during EVHP. We conclude that the avoidance of profound hypothermia during IR minimizes injury and improves the functional recovery of DCD hearts.Abbreviations: C a O 2 , oxygen content in arterial blood (aortic root); C v O 2 , oxygen content in venous blood (pulmonary artery); CBF, coronary blood flow; CVR, coronary vascular resistance; DCD, donation after circulatory death; dP/dt maximum, maximum rate of pressure change in the left ventricle; dP/dt minimum, minimum rate of pressure change in the left ventricle; EVHP, ex vivo heart perfusion; MVO 2 , myocardial oxygen consumption; P a O 2 , partial pressure of oxygen in arterial blood (aortic root); P v O 2 , partial pressure of oxygen in venous blood (pulmonary artery)

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Section: Discussionmentioning

confidence: 99%

Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death

White

Ambrose

Müller

et al. 2016

American Journal of Transplantation

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“…Ischemic tolerance substantially varies between different organs. Because of the enhanced susceptibility of the cardiac allograft, it is of utmost importance to keep cold ischemic time below 4 hours in heart transplantation (Taylor et al, 2009;Jacobs et al, 2010). A considerable number of heart transplants are still performed after prolonged cold ischemia, which promotes early graft dysfunction and increases mortality post-transplantation (Taylor et al, 2009).…”

Section: Dopamine and Its Lipophilic Derivates Providementioning

confidence: 99%

Dopamine and Lipophilic Derivates Protect Cardiomyocytes against Cold Preservation Injury

Vettel

Hottenrott

et al. 2013

J Pharmacol Exp Ther

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Donor heart allografts are extremely susceptible to prolonged static cold storage. Because donor treatment with low-dose dopamine improves clinical outcome after heart transplantation, we tested the hypothesis that dopamine and its lipophilic derivate, N-octanoyl dopamine (NOD), protect cardiomyocytes from cold storage injury. Neonatal rat cardiomyocytes were treated with dopamine or NOD or left untreated and subsequently subjected to static cold storage (8-12 hours). Dopamine-and NOD-treated cardiomyocytes displayed a better viability compared with untreated cells after hypothermia. In untreated cardiomyocytes, cell damage was reflected by lactate dehydrogenase (LDH) release and a decrease in intracellular ATP. NOD was approximately 20-fold more potent than dopamine. Similarly to cardiomyocytes in vitro, rat hearts perfused with NOD before explantation showed significantly lower LDH release after static cold storage. ATP regeneration and spontaneous contractions after cold storage and rewarming only occurred in treated cardiomyocytes. Hypothermia severely attenuated isoprenaline-induced cAMP formation in control but not in dopamine-or NOD-treated cells. Esterified derivates of NOD with redox potential and lipophilic side chains reduced cell damage during cold storage similarly to NOD. In contrast to dopamine, neither NOD nor its derivates induced a significant b-adrenoceptor-mediated elevation of cellular cAMP levels. The b 1 -adrenoceptor antagonist atenolol and D 1 /D 2 receptor antagonist fluphenazine had no impact on the protective effect of NOD or dopamine. We conclude that dopamine as well as NOD treatment mitigates cold preservation injury to cardiomyocytes. The beneficial effects are independent of b-adrenoceptor or dopaminergic receptor stimulation but correlate with redox potential and lipophilic properties.

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“…The ideal situation -that disruption of blood supply to the organ to be transplanted until restoration of the circulation by the recipient is so short that cooling of the organ is not necessary -is rare and organs to be transplanted are in most cases stored for 3-48 h at low temperature. To minimize negative effects of 'cold ischemia-reperfusion injury', specific protocols of cooling and rewarming and usage of different preservation solutions have been elaborated [1][2][3][4][5][6][7][8]. These, however, do not fully eliminate the negative effects of storage at low temperature on the functionality of transplanted organs, contributing to their failure.…”

Section: Introductionmentioning

confidence: 99%

Cold induces reactive oxygen species production and activation of the NF‐kappa B response in endothelial cells and inflammation in vivo

Awad

Khan

Sokolikova

et al. 2013

Journal of Thrombosis and Haemostasis

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Summary. Background: Organs intended for transplantation are generally stored in the cold for better preservation of their function. However, following transplantation and reperfusion, the microvasculature of transplanted organs often proves to be activated. Extensive leukocyte adhesion and microthrombus formation contribute to failure of the transplanted organ. Objectives: In this study we analyzed cold-induced changes to the activation status of cultured endothelial cells, possibly contributing to organ failure. Methods: We exposed human umbilical vein endothelial cells (HUVECs) to temperatures below 37°C (mostly to 8°C) for 30 min and upon rewarming to 37°C kept incubating them for up to 24 h. We also in vivo locally exposed mice to cold. Results: The exposure to low temperatures induced, in HUVECs, expression of the prothrombotic factors plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and of the inflammatory adhesion molecules, E-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, upon rewarming for 30 min, we detected activation of the inflammatory NF-jB pathway, as measured by transient NF-jB translocation to the nucleus and IjBa degradation. Using butylated hydroxytoluene (BHT), a scavenger of reactive oxygen species (ROS), we further demonstrated that cold-induced NF-jB activation depends on ROS production. Local exposure to cold also, in vivo, induced ROS production and ICAM-1 expression and resulted in leukocyte infiltration. Conclusions: Our results point to a causative link between ROS production and NF-jB activation, suppression of which had been shown to be beneficial during hypothermic storage and subsequent rewarming of organs for transplantation.

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Current preservation technology and future prospects of thoracic organs. Part 2: heart

Cited by 32 publications

References 46 publications

Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death

Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death

Dopamine and Lipophilic Derivates Protect Cardiomyocytes against Cold Preservation Injury

Cold induces reactive oxygen species production and activation of the NF‐kappa B response in endothelial cells and inflammation in vivo

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