Energy status of pig donor organs after ischemia is independent of donor type

Stadlbauer, Vanessa; Stiegler, Philipp; Taeubl, Philipp; Sereinigg, Michael; Puntschart, A.; Bradatsch, Andrea; Curcic, Pero; Seifert-Held, Thomas; Zmugg, Gerda; Stojaković, Tatjana; Leopold, Barbara; Blattl, Daniela; Horki, Vera; Mayrhauser, Ursula; Wiederstein-Grasser, Iris; Leber, Bettina; Jürgens, Günther; Tscheliessnigg, Karlheinz; Hallström, Seth

doi:10.1016/j.jss.2012.05.025

Cited by 10 publications

(13 citation statements)

References 56 publications

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“…Pulsatile perfusion, on the other hand, was associated with the preservation of endothelial cell integrity, which could have significant benefits on clinical outcomes both in the short-term (less primary graft failure) and long-term (less CAV). There was no significant ATP depletion after 4 h in either group, which is consistent with the literature [25]. …”

Section: Discussionsupporting

confidence: 92%

Preservation of Donor Hearts Using Hypothermic Oxygenated Perfusion

et al. 2014

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Background Hypothermic machine perfusion of donor hearts enables continuous aerobic metabolism and washout of toxic metabolic byproducts. We evaluated the effect of machine perfusion on cardiac myocyte integrity in hearts preserved for 4 h in a novel device that provides pulsatile oxygenated hypothermic perfusion (Paragonix Sherpa Perfusion™ Cardiac Transport System). Material/Methods Pig hearts were harvested and stored in Celsior® solution for 4 h using either conventional cold storage on ice (4-h CS, n=6) or the Sherpa device (4-h pulsatile perfusion (PP), n=6). After cold preservation, hearts were evaluated using a non-working heart Langendorff system. Controls (n=3) were reperfused immediately after organ harvest. Biopsies were taken from the apex of the left ventricle before storage, after storage, and after reperfusion to measure ATP content and endothelin-1 in the tissue. Ultrastructural analysis using electron microscopy was performed. Results Four-hour CS, 4-h PP, and control group did not show any significant differences in systolic or diastolic function (+dP/dt, −dP/dt, EDP). Four-hour PP hearts showed significantly more weight gain than 4-h CS after preservation, which shows that machine perfusion led to myocardial edema. Four-hour CS led to higher endothelin-1 levels after preservation, suggesting more endothelial dysfunction compared to 4-h PP. Electron microscopy revealed endothelial cell rupture and damaged muscle fibers in the 4-h CS group after reperfusion, but the cell structures were preserved in the 4-h PP group. Conclusions Hypothermic pulsatile perfusion of donor hearts leads to a better-preserved cell structure compared to the conventional cold storage method. This may lead to less risk of primary graft failure after orthotopic heart transplantation.

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Section: Discussionsupporting

confidence: 92%

Preservation of Donor Hearts Using Hypothermic Oxygenated Perfusion

et al. 2014

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“…169/1999) and experiments were performed in accordance with the NIH guide for the care and use of laboratory animals [21]. Organ procurement from BD (n = 6) and LD animals (n = 6) was performed according to the local standards [22] and the EUROTRANSPLANT guidelines [23]. For BD a slow BD induction model was used as described elsewhere; briefly, after drilling a burr hole in the right frontoparietal region of the skull, a Foley catheter was inserted into the subdural space.…”

Section: Methodsmentioning

confidence: 99%

“…The balloon of the catheter was inflated with saline solution at a rate of 3 ml every 30 seconds to a total volume of 24 ml. Animals were kept at a mean arterial pressure of 50 mmHg and animals were stabilized for 10 hours according to local donor management guidelines [22,24]. 60 min after total inflation of the balloon, anaesthesia was discontinued and after a period of another 60 min, BD diagnostic was performed including testing of brain stem reflexes and painful stimuli by a neurologist, followed by apnoea testing and a 30 min 8 - channel EEG exactly as described elsewhere [25].…”

Section: Methodsmentioning

confidence: 99%

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

et al. 2013

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BackgroundAs organ shortage is increasing, the acceptance of marginal donors increases, which might result in poor organ function and patient survival. Mostly, organ damage is caused during brain death (BD), cold ischemic time (CIT) or after reperfusion due to oxidative stress or the induction of apoptosis. The aim of this study was to study a panel of genes involved in oxidative stress and apoptosis and compare these findings with immunohistochemistry from a BD and living donation (LD) pig model and after cold ischemia time (CIT).MethodsBD was induced in pigs; after 12 h organ retrieval was performed; heart, liver and kidney tissue specimens were collected in the BD (n = 6) and in a LD model (n = 6). PCR analysis for NFKB1, GSS, SOD2, PPAR-alpha, OXSR1, BAX, BCL2L1, and HSP 70.2 was performed and immunohistochemistry used to show apoptosis and nitrosative stress induced cell damage.ResultsIn heart tissue of BD BAX, BCL2L1 and HSP 70.2 increased significantly after CIT. Only SOD2 was over-expressed after CIT in BD liver tissue. In kidney tissue, BCL2L1, NFKB, OXSR1, SOD2 and HSP 70.2 expression was significantly elevated in LD. Immunohistochemistry showed a significant increase in activated Caspase 3 and nitrotyrosine positive cells after CIT in BD in liver and in kidney tissue but not in heart tissue.ConclusionThe up-regulation of protective and apoptotic genes seems to be divergent in the different organs in the BD and LD setting; however, immunohistochemistry revealed more apoptotic and nitrotyrosine positive cells in the BD setting in liver and kidney tissue whereas in heart tissue both BD and LD showed an increase.

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“…The assessment of free fluctuating concentrations of these metabolites would require 31P NMR and a number of near equilibrium expressions using the creating kinase and adenylatekinase equilibrium [23]. However, energy charge as calculated value from the absolute concentrations of AMP, ADP and ATP has been proven to be a valuable parameter for energetic situations of cells and tissue [24-26]. …”

Section: Discussionmentioning

confidence: 99%

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

et al. 2013

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IntroductionRewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.MethodsForty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.ResultsThe slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.ConclusionsLevosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.

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Energy status of pig donor organs after ischemia is independent of donor type

Cited by 10 publications

References 56 publications

Preservation of Donor Hearts Using Hypothermic Oxygenated Perfusion

Preservation of Donor Hearts Using Hypothermic Oxygenated Perfusion

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

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