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Original Basic Science—General

Pathophysiological Trends During Withdrawal of Life Support

Implications for Organ Donation After Circulatory Death

Iyer, Arjun MBBS; Chew, Hong Chee MBBS; Gao, Ling PhD; Villanueva, Jeanette PhD; Hicks, Mark PhD; Doyle, Aoife MEngSc; Kumarasinghe, Gayathri MBBS; Jabbour, Andrew MBBS, PhD; Jansz, Paul Cassius MBBS, PhD; Feneley, Michael P. MBBS, MD; Harvey, Richard P. PhD; Graham, Robert M. MBBS, MD; Dhital, Kumud K. MBBS, PhD; Macdonald, Peter S. MBBS, MD, PhD

Author Information
doi: 10.1097/TP.0000000000001396
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A significant disparity exists between the demand for heart transplantation and the availability of suitable donor organs, resulting in substantial mortality of patients on waiting lists around the world.1 Although the utilization of lungs from donation after circulatory death (DCD) donors has changed the landscape of lung transplantation in Australia since 2006,2 the utilization of hearts from such donors has rarely been attempted.3,4 Concerns regarding myocardial damage during the obligatory warm ischemic time (WIT) that accompanies withdrawal of life support (WLS) and the inability to assess viability of cold-stored hearts has limited clinical translation.

Several preclinical studies and recent clinical reports have reported viability and successful orthotopic transplantation of DCD hearts4-8; however, questions remain regarding the maximal tolerable WIT and the ideal preservation strategy. Cessation of ventilatory support at withdrawal in the setting of poor respiratory drive results in profound hypoxemia. Although continued exposure to alveolar air limits hypoxic injury to DCD lungs,9,10 organs reliant on oxygenated blood perfusion, such as the heart, lack this advantage. In addition, high aerobic dependence of the heart renders it particularly vulnerable to ischemic injury.11

Another potential cardiac insult after WLS is ventricular distension. With decreasing ejection and increasing end-diastolic volumes, the heart is exposed to progressively higher intraventricular pressures. Detrimental effects of ventricular distension have been reported in cardiac surgery12 and during the DCD withdrawal period.13,14

Now that heart transplantation from DCD donors is a clinical reality, an important goal of ongoing research is to improve the tolerability of the DCD heart to warm ischemia. With this goal in mind, the aim of the present study was to provide a detailed description of the pathophysiological changes after WLS in a porcine DCD model. To this end, central hemodynamic and ventricular volumetric changes, blood gas derangements, as well as myocardial catecholamine release were assessed over a range of WITs.


Details of the animals used and study protocol have been reported previously.7 Juvenile Landrace pigs were used, with experimental protocols approved by the Garvan/St Vincent's Animal Ethics Committee. All animals were cared for according to the standards outlined in the Australian Code for the Care and Use of Animals for Scientific Purposes 8th edition (2013) and overseen by the Garvan/St. Vincent's Hospital Animal Ethics Committee.

Animals and Anesthesia

Forty-two pigs weighing 55 to 65 kg were used. Animals were premedicated with intramuscular ketamine (10 mg/kg), midazolam (1 mg/kg), and atropine (50 μg/kg). Animals were intubated using cuffed 7 to 7.5 mm endotracheal tubes, with anaesthesia induced/maintained using inhalational isoflurane (2-5%) and intravenous fentanyl (100-200 μg bolus).

Ventilation was maintained with a tidal volume of 10 mL/kg, positive end-expiratory pressure of 5-7 mm Hg.

Mean arterial pressure (MAP), central venous pressure (CVP), pulse oximetry and electrocardiogram were monitored. Arterial blood gases were analyzed regularly, including presurgical baselines.

Surgical Procedure and DCD Protocol

The right internal carotid artery (RICA; 5Fr) and right internal jugular vein (RIJV; 8Fr) were cannulated for arterial and CVP monitoring. A median sternotomy was performed, and the pericardium opened.

Series 1

An asphyxia model was used to mimic the clinical setting. Heparin (300 mg/kg) was administered intravenously before WLS. After bolus dose of midazolam (10 mg) and fentanyl (100 μg) to ensure sedation and analgesia, ventilation was ceased and endotracheal tube disconnected. Absence of spontaneous breathing was confirmed. Times to circulatory arrest and electrical asystole were recorded; however, hearts were left untouched for predetermined periods of warm ischemia (between 20 and 40 minutes), irrespective of electrical activity/circulatory cessation times.

Warm ischemia was defined as the period between withdrawal of ventilator support and administration of preservation solution. Circulatory arrest was defined as the time when MAP matched CVP. The groups were assigned as outlined in Table 1.

Groups exposed to varying predetermined warm ischaemic times, irrespective of time to circulatory arrest

Immediately before the end of predetermined WIT, cannulae were inserted into right atrium (for blood collection) and aortic root (for administration of preservation solution). Blood (~1.2 L) was drained just before aortic cross-clamping and administration of Celsior preservation solution, (Genzyme, Cambridge, MA; 1 L precooled to 4°C), with the heart vented via incisions in the left atrial appendage and inferior vena cava, and the chest cavity filled with cold slush.

These experiments were performed to assess recovery of DCD hearts exposed to varying WITs on an ex vivo perfusion (EVP) circuit as reported previously.7 Donor animal blood was used as perfusate, with 2 separate methods of blood collection assessed. Using 40Fr single stage venous cannula in the right atrium, blood was drained into a collection bag with roller pump assistance in 1 group and by simple gravity drainage in the second group—gravity-assisted blood collection was performed in a separate group of 6 animals exposed to 30-minute WIT (in addition to the 12 × 30 minutes WIT animals reported in Table 1).

Outcome Measures

Hemodynamic changes, biochemical alterations, and hormonal responses were assessed at baseline and during WLS. Blood analysis was performed in all animals at 3 set timepoints: prewithdrawal, 5 min postwithdrawal, and immediately postelectrical asystole. Further sampling times were based on the predetermined WIT, and not all parameters were measured at all timepoints. The number of observations at each timepoint varied according to the time to electrical asystole and the subsequent WIT.

Hemodynamic Changes

Mean arterial pressure and CVP and oxygen saturations (left ear pulse oximeter) were measured at presurgical, prewithdrawal, and at set timepoints during the withdrawal period (n = 24; saturation measures are reported in 22/24, because 2 experiments had technical issues with the probe).

Blood Gas Changes

Blood gases were analysed using the iSTAT “point of care” handheld analyzer with EG-6 cartridges (Abbott Inc, Princeton, NJ). This provided additional measures of the partial pressures of O2 and CO2, oxygen saturations, and pH (n = 6-24).

Biochemical Changes

Troponin-T was measured in arterial blood at presurgical, prewithdrawal, and regular postwithdrawal timepoints (n = 5-20) using chemiluminescence immunoassay (Roche E170 immunoassay). Potassium, bicarbonate, and lactate concentrations were measured in arterial blood at corresponding timepoints using the iSTAT analyzer (n = 5-24). In addition, potassium levels in withdrawn blood were compared between the 2 blood collection methods (n = 6-18).

Catecholamine Levels

Whole blood samples were taken simultaneously from the RICA and a nonoccluding coronary sinus catheter for measurement and comparison of systemic and local myocardial adrenaline and noradrenaline release (n = 5). Catecholamine levels were measured using a Shimadzu HPLC-ECD Antec-Leydon detector.

Series 2

An additional 12 experiments were performed to more closely investigate the central hemodynamic and ventricular volumetric changes during the first 10 minutes of the withdrawal period. In this set of experiments, no antemortem heparin was administered. In addition to the previously mentioned invasive monitoring methods, a Swan-Ganz catheter was introduced into the RIJV for pulmonary artery pressure (PAP) measurement. After sternotomy, the left atrium was cannulated to allow continuous measurement of left atrial pressure (LAP). Sonometric crystals were used to measure volumetric changes in the ventricles during withdrawal (left ventricle n = 6; right ventricle n = 6). Five crystals were attached to the epicardium of a single ventricle ((1) apical, (2) basal, (3) anterior wall, (4) posterior wall, (5) septal wall), and a Millar pressure catheter was inserted into the corresponding ventricle.

Hemodynamic and Volume Changes

Mean arterial pressure, CVP, PAP, LAP, left or right ventricular volume, and intracavitary pressure were recorded at baseline and from the beginning of WLS until asystole. We used SonoSOFT 3.1.3 Software (Sonometrics Corp., London, ON) to acquire and analyze the data files as described previously.15

Statistical Methods

Statistical analyses were performed using Prism 6.0b (GraphPad Software, Inc, La Jolla, CA). Normally, distributed data are expressed as mean ± SE. Nonparametric data are expressed as median values. Differences between groups were determined using 1- or 2-way analysis of variance depending on the number of factors assessed; followed by post hoc analysis using Tukey test to correct for multiple comparisons. Nonparametric data were compared using the Mann-Whitney test. A P value less than 0.05 was considered significant.


Series 1

Haemodynamic changes

After WLS, there was an immediate and progressive fall in systemic arterial pressure. Central venous pressure rose within the first 5 minutes after withdrawal. Mean time from withdrawal to circulatory cessation (MAP = CVP) was 8 ± 1 min (Figure 1A). During the first 2 to 3 minutes after WLS, there was a small increase in heart rate. Thereafter, heart rate fell progressively (Figure 1B). Time to electrical asystole was significantly longer than time to cessation of circulation occurring at a mean of 16 ± 2 minutes postwithdrawal with 6 animals demonstrating electrical activity beyond 25 minutes (Figure 1C).

A, Systolic and diastolic BP, MAP, and CVP during withdrawal period (n = 24) expressed as mean ± SE. B, Mean heart rate during 30 minutes postwithdrawal, displayed as bpm (n = 24) expressed as mean ± SE; (c) of the 24 hearts evaluated, time to electrical silence (asystole) reported as number of animals during each time interval. bpm, beats per minute.

Blood Gas and pH Changes

Oxygen saturation was measured invasively (SO2-RICA) and noninvasively (SaO2-ear oximetry). SaO2 fell rapidly from 100% to below 30% by 2 minutes postwithdrawal (Figure 2A). SO2 confirmed similar findings, with SO2 falling to 12% ± 1% at 5 minutes postwithdrawal. The partial pressure of oxygen fell rapidly to 14 ± 1 mm Hg by 5 minutes postwithdrawal, whereas carbon dioxide increased to 84 ± 3 mm Hg (Figure 2B). Profound acidosis developed during the WIT-pH (Figure 3A) decreased to 7.17 ± 0.01. A progressive lactic acidosis was evident with increasing WIT-blood lactate levels peaked at 13 ± 2 mmol/L at 40 minutes postwithdrawal (Figure 3B).

A, Noninvasive oxygen saturations—SaO2 readings of ear probe; n = 22 (of total n = 24, 2 experiments encountered technical issues with the saturation probe); graph demonstrates the rapid onset of hypoxia in the presence of asphyxia; expressed as mean ± SE. B, PaO2 and PaCO2 was measured over the 30 min WIT period (n = 6-24) expressed as mean ± SE. PaO2, partial pressure of oxygen; PaCO2, carbon dioxide.
A, pH levels during the withdrawal period. The bar on the left indicates normal pH before withdrawal, and the shaded territory indicates the normal pH range of 7.35 to 7.5 (n = 6-24) expressed as mean ± SE. B, Mean lactate levels at various time-points prior to and after withdrawal. Lactate levels in mmol/L (n = 5-24) expressed as mean ± SE.

Biochemical Changes

Blood troponin-T levels rose progressively during the WIT (Figure 4), peaking at 202 ± 26 ng/L at 40 minutes postwithdrawal. Blood potassium concentrations [K+] increased from a baseline level of 3.9 ± 0.3 mmol/L to 5.6 ± 0.1 mmol/L by 5 minutes postwithdrawal. Thereafter, no further significant increases were noted during in situ sampling (Figure 5A).

Troponin T levels at timepoints before and after withdrawal. Troponin measured as ng/L (n = 5-20) expressed as mean ± SE.
A, In vivo measurement of potassium levels before and after withdrawal of ventilator support. Potassium (K+) as mmol/L (n = 7-24) expressed as mean ± SE. B, Ex vivo measurement of potassium, sampled from pump assisted blood collected after varying WIT periods (20-40 min; n = 6-24. C, Ex vivo measurement of potassium, sampled from either gravity assisted (n = 6) or pump-assisted methods (n = 12) after the same 30 minutes WIT period. Both graphs display in vivo prewithdrawal potassium levels as control. Potassium (K+) as mmol/L; expressed as mean ± SE.

[K+] of samples from blood collected (for EVP) using a roller pump are displayed in Figure 5B. [K+] of collected blood rose dramatically with increasing WIT before blood collection (Figure 5B). When the same quantity of blood was collected using gravity drainage after 30 minutes WIT, there was only a small nonsignificant increase in the [K+] in the collected blood compared with the in situ [K+] after 30 minutes WIT (in situ [K+] after 30 minutes WIT 5.9 ± 0.2 mmol/L versus [K+] in blood collected with gravity assistance 6.3 ± 0.5 mmol/L, p = ns). In contrast, [K+] in blood collected with roller pump assistance after 30 minutes WIT was markedly elevated reaching 10.5 ± 0.7 mmol/L (P < 0.001 vs in situ [K+] or [K+] in blood collected by gravity drainage; Figure 5C).

Catecholamine Levels

Simultaneous measures of adrenaline and noradrenaline from carotid artery and coronary sinus catheters revealed elevations of both catecholamines postwithdrawal (Figure 6; n = 5). There was a significant increase in both amines at both locations at 4 minutes postwithdrawal compared with baseline. At 20 minutes, there was further increase of both amines in blood sampled from the coronary sinus but not from the carotid artery.

Median adrenaline (A) and noradrenaline (B) levels during warm ischaemia period postwithdrawal. Measured in nmol/L (n = 5). Differences between sampling sites and time points analyzed using nonparametric Mann-Whitney U test.

Series 2

Baseline pressure measurements in all animals were MAP, 65 ± 10 mm Hg; PAP, 17 ± 3 mm Hg; CVP, 6 ± 2 mm Hg; LAP, 8 ± 1 mm Hg. After cessation of ventilation, a progressive decrease in MAP was noted as in series 1. In contrast to the progressive decline in MAP, there was an initial rise in CVP and PAP (to 12 ± 3 mm Hg; and 21 ± 3 mm Hg, respectively, both P < 0.05 compared with baseline). Simultaneously with the rise in CVP and PAP, LAP fell reaching a nadir of 6 ± 3 mm Hg (P < 0.05 vs baseline). With progression to mechanical asystole, all pressures eventually equalized (PAP, 8 ± 1 mm Hg; CVP, 8 ± 1 mm Hg; LAP, 8 ± 2 mm Hg) (Figure 7).

Central haemodynamic changes during withdrawal of life support (n = 12).

Volume Changes

Representative pressure volume loops for the right and left ventricles during the first 5 minutes after WLS are shown in Figure 8. In the right ventricle, the end-diastolic pressure volume point was displaced upward and to the right, whereas the end-diastolic pressure volume point for the left ventricle was displaced downward and to the left. Mean baseline right and left ventricular volumes were 162 ± 30 mL and 159 ± 52 mL, respectively. Measurements were calculated at minute intervals until equalization of central hemodynamic pressures. After WLS, right ventricle end-diastolic volume increased by 23% to 199 ± 57 mL (P = 0.083 vs baseline, 1-sided P value) and left ventricle end-diastolic volume increased by 4% to 169 ± 49 mL (Figure 9).

Representative pressure volume loops obtained from RV and LV during withdrawal of life support. RV, right ventricle; LV, left ventricle.
Changes in LV and RV volumes during withdrawal of life support (n = 12).


This study demonstrates in a porcine asphyxia model that the absence of respiratory drive after WLS results in rapid onset of profound hypoxemia with progression to circulatory arrest within 10 minutes in most animals. Significantly longer times to electrical asystole when compared with circulatory arrest times were noted. No cases of autoresuscitation were observed after circulatory arrest. The presence of ongoing electrical activity in the absence of cardiac output has also been reported in human DCD donors.16,17 Importantly, from a clinical standpoint, death is determined at the time of cessation of the circulation and not electrical asystole which can persist for many minutes after circulatory arrest.

A definition of functional warm ischemia as the interval between systemic arterial systolic pressure of less than 50 mm Hg and the administration of organ flush solution has been proposed for the lungs, liver, and kidneys of DCD donors.10,18,19 A number of observations in our model suggest that the onset of myocardial ischemia in the DCD donor may occur earlier than the onset of ischemia for other organs. As shown in Figure 1, systolic blood pressure fell below 50 mm Hg within the first 5 minutes, at which time diastolic blood pressure was only 20 mm Hg. Given that the majority of coronary blood flow occurs during diastole, it is likely that the onset of coronary hypoperfusion and myocardial ischemia occurs well before systolic blood pressure reaches 50 mm Hg. Lung tissue, even in the absence of adequate perfusion, can maintain tissue ATP levels through alveolar oxygen exposure.9 This differs from other organs including the heart where coronary perfusion remains the sole avenue of oxygen delivery. In our model, profound hypoxemia developed rapidly with the arterial oxygen saturation falling from 100% prewithdrawal to 30% within 2 minutes of cessation of ventilation, when systolic blood pressure was still above 50 mm Hg (Figures 1 and 3).

Along with the rapid desaturation, occurring within 2 minutes after withdrawal, we observed a significant increase in PAP and CVP and a significant fall in LAP. These changes are most likely due to hypoxemia-induced acute pulmonary vasoconstriction, resulting in increased right ventricular afterload and decreased left ventricular preload. Acute hypercapnia and acidosis or elevation of endothelin-1 may also contribute to the pulmonary vasoconstrictor response.20,21 Although both ventricles are subjected to profound normothermic ischemia, these observations suggest that there is an additional insult to the right ventricle, resulting from the abrupt increase in pulmonary vascular impedance. The differential effect of WLS on the diastolic filling pressures in the right and left ventricles (as reflected by the CVP and LAP, respectively) also has implications for the rate of decline in coronary blood flow to each ventricle. As coronary perfusion pressure is largely determined by the difference between aortic diastolic perfusion pressure and intraventricular diastolic pressure, the more rapid loss of the perfusion gradient between aortic diastolic pressure and the right ventricular pressure, as approximated by the CVP (as compared with the pressure gradient between aortic diastolic pressure and the left ventricular pressure, as approximated by the LAP) suggests that right ventricular myocardial perfusion is compromised more rapidly than left ventricular perfusion.

Our findings complement those reported recently by White et al14 in a similar porcine model of DCD donation. In that study, the authors inferred a pulmonary vasoconstrictor response based on changes in the left and right ventricular pressures after WLS, but they did not directly measure PAP or LAP. These authors also reported a 20% increase in the right ventricular end-diastolic volume during WLS with a small fall in left ventricular volume. Although the change in right ventricular volume observed in our study during WLS did not reach statistical significance, the magnitude of the change was identical to that reported by White et al.14 Although hypoxia and hypoperfusion are obligatory insults in all DCD organs, the additional insult of distension is likely to impact negatively on recovery13,14—ventricular distension contributes to decreased diastolic coronary flow, subendocardial ischemia, overstretch of cardiac muscle, and damage to the endocardium.22 Regardless of the mechanism, our observations suggest that the right ventricle suffers a more severe insult than the left ventricle during WLS in the DCD setting. Although the clinical implications of this finding remains uncertain, the additional insult to the right ventricle suggests that caution should be exercised in the selection of recipients for hearts obtained from DCD donors, avoiding recipients with fixed elevation of pulmonary vascular resistance. The greater right ventricular injury apparently mediated by pulmonary vasoconstriction raises the potential role of prophylactic pulmonary vasodilator therapy in management of WLS before recovery of DCD hearts. There is some experimental evidence for this with Kato et al23 demonstrating in a canine model of DCD heart donation that intravenous administration of the endothelin antagonist, FR139317, 10 minutes before WLS, blunted the rise in PAP during WLS and was associated with better recovery of the donor heart after transplantation. As with other antemortem interventions, the administration of pulmonary vasodilator therapy before WLS would need careful ethical consideration and jurisdictional approval.

Cardiac myocyte death is an inevitable consequence of progressive hypoxia and acidosis.24-26 Withdrawal of life leads to the rapid development of both these conditions with progressive lactic acidemia (>10 mmol/L) and hypercarbia (>80 mmHg) contributing to severe acidosis. The correlation between WIT and troponin rise observed in our study is in keeping with progressive myocardial damage with longer periods of exposure to the above insults. Acidosis during myocardial ischemia activates the sodium hydrogen exchanger, NHE1, which may contribute to myocardial dysfunction both during ischemia and upon reperfusion.26 Administration of selective inhibitors of the NHE1 after the onset of ischemia but before the onset of reperfusion has been shown to reduce myocardial injury in experimental models of normothermic ischemia reperfusion injury including sustained cardiac arrest,27 and for this reason, inhibition of NHE1 is an attractive therapeutic target for myocardial protection in DCD donors.7,28

Significant changes in potassium levels were also evident during WIT. Acidosis is the most likely cause for this rapid development. It is uncertain whether other factors, such as myocyte necrosis or red cell hemolysis, contribute to this early rise; however, it is noteworthy that no further increase in potassium was observed in vivo after circulatory arrest. Subsequent collection of donor blood from the right atrium using a large bore cannula with gravity assistance was associated with little change in the potassium concentration of collected blood. In contrast, the progressive increase in potassium concentration of blood collected using a roller pump suggests increased fragility of red cells with increasing WIT. Although plasma free hemoglobin was not measured, the dramatic further increase in blood potassium observed with roller pump-assisted blood collection is most likely explained by mechanical disruption of fragile red cells by the pump.

The catecholamine storm of brain dead donors has been associated with detrimental donor organ function.15,29,30 It has been suggested that the absence of this in DCD donors may contribute to potentially superior outcomes in lung transplant recipients.2,31 This hypothesis has been challenged however by findings from Ali et al5 in a porcine model in which they observed similar or greater catecholamine release in DCD donors compared with brain stem death donors. The increase in heart rate observed within the first few minutes of WLS in our study and also reported by others may be explained by activation of the sympathetic nervous system in response to falling systemic blood pressure and hypoxemia as recently suggested by White et al.14 Our observation of a higher coronary sinus level of noradrenaline and adrenaline (compared with systemic measures) at 4 and 20 minutes is consistent with dramatic release of myocardial catecholamines during and after WLS. These data suggest that the presence of a catecholamine surge in DCD donors, similar to that observed in brain dead donors, however the extent of catecholamine-induced injury to the heart and exposure of other organs to these damaging catecholamines in the setting of a rapidly deteriorating circulation is unclear.

If DCD hearts are to become a viable option for cardiac transplantation, EVP technology will likely play an important role in resuscitation of these organs. This is an active area of research with ongoing debate about the ideal perfusate.5,6,8,32 A normothermic blood-based perfusate, allowing provision for oxygenation and therefore beating heart assessment, seems to be the leading contender.6,32 Although donor blood is an easily accessible resource, the time required for its collection (up to 90 seconds in clinical cases reported to date),4 introduces a further delay in the recovery of other organs. In addition, as shown in the present study, blood collected from DCD donors has marked abnormalities in its composition—it is markedly acidotic and hyperkalemic, with further potassium rise encountered when blood collection is undertaken using roller pump-assisted instead of gravity-assisted collection. Furthermore, increased levels of catecholamines in collected blood could also adversely affect cardiomyocyte survival and myocardial function.5 These findings highlight the need for further research aimed at optimizing the composition of the perfusate used for EVP of DCD hearts to limit further organ damage.


Several limitations must be noted. First, the donors were healthy adolescent animals that were anesthetized before WLS. In the clinical setting, most potential DCD donors have sustained critical neurological injuries and have been on life support for days before a decision to WLS. Moreover, the time to circulatory arrest after WLS is difficult to predict with only a minority of DCD donors progressing as rapidly as the porcine model used in our experiments.33 Although the time to circulatory arrest reported in our study was similar to that reported by others using similar open-chested porcine models,13,14,23 longer times to circulatory arrest have been reported by authors examining recovery of abdominal organs in porcine DCD models where the chest cavity has been left intact.34,35 Second, the standoff period in series 1 was greater than would be allocated clinically. This was done to expose the donor hearts to set warm ischemic times, irrespective of circulatory cessation time. In addition, the use of isoflurane anaesthesia in our model and similar large animal DCD models reported by others13,14,23,34,35 is another point of difference between the experimental laboratory and the clinical setting. A potential preconditioning effect of isoflurane anaesthesia in these animals before WLS cannot be excluded36; however, we think this is unlikely to have influenced the tempo of hemodynamic and metabolic changes that occurred during the normothermic ischemia because we have previously demonstrated a potent postconditioning effect of supplemented Celsior solution in DCD hearts recovered from isoflurane-anesthetized animals.7 Finally, the antemortem administration of heparin in series 1 is not permitted in some jurisdictions.


The need for an additional source of cardiac allografts in transplantation is great, and DCD hearts offer a potential source of organs. A better understanding of the detrimental processes that occur during the warm ischemic period is needed and may provide insights into optimal resuscitation of these hearts. In these series of experiments, we have demonstrated the profound hemodynamic, biochemical, and hormonal derangements that occur during the warm ischemic period with a disproportionate injury to the right ventricle caused by acute pulmonary vasoconstriction. Although many of these insults cannot be avoided, there is scope for (ethically acceptable) antemortem and postmortem interventions to limit the profound hemodynamic and metabolic derangements and progress to be made in identifying and optimizing a suitable perfusate for EVP.


The authors gratefully acknowledge the generous support of St Vincent's Hospital's clinical perfusion service led by Dr Frank Junius. Their technical and material support was invaluable for the conduct of this study.


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