N e w Te c h n i q u e s f o r O p t i m i z a t i o n o f D o n o r L u n g / H e a r t s

Injuries sustained by donor heart and lung allografts during the transplantation process are multiple and cumulative. Optimization of allograft function plays an essential role in short- and long-term outcomes after transplantation. Therapeutic targets to prevent or attenuate injury are present in the donor, the preservation process, during transplantation, and in postoperative management of the recipient. The newest and most promising methods of optimizing donor heart and lung allografts are found in alternative preservation strategies, which enable functional assessment of donor organs and provide a modality to initiate therapies for injured allografts or prevent injury during reperfusion in recipients.

procedure. Annually, approximately 4100 lung transplants are performed worldwide 1 (Fig. 1, survival demonstrated in Fig. 2), a number that has stagnated in recent years because of a limit in the number of available donor lungs.
In contrast to end-stage respiratory failure, most patients with terminal heart failure have an alternative to heart transplant for the medium or long term in the form of mechanical circulatory support (MCS). One of the major indications for long-term MCS is to "bridge" the wait to transplantation for otherwise terminal heart-failure patients, offering the opportunity for clinical improvement and preventing worsening secondary end-organ damage. However, for younger patients, or patients who poorly tolerate MCS (eg, biventricular failure, or issues with MCS such as drive-line infections or gastrointestinal bleeding), heart transplant remains the preferred therapy. Annually, approximately 5000 heart transplants are performed worldwide (Fig. 3, with survival according to preoperative MCS support shown in Fig. 4).
The common themes dominating heart and lung transplantation are the shortage of standard donor organs (Box 1, Table 1) and an increasingly complex recipient population, both factors that adversely affect waiting-list and transplant outcomes. Fortunately, new techniques are being developed to optimize donor heart and lung allograft function to both improve outcome and quality of life after transplant and to expand the donor pool by using "nonstandard" or marginal allografts. This review explores the clinical relevance of donor heart and lung allograft injury, mechanisms of injury, and ways in which to optimize donor heart and lung allograft function.

CLINICAL RELEVANCE OF PRIMARY GRAFT DYSFUNCTION/FAILURE IN HEART TRANSPLANTATION
In 2011 a definition of primary graft failure (PGF) after heart transplantation (HTx) was proposed based on a retrospective analysis of 621 consecutive heart transplants, 2 resulting in 4 criteria: 1. Significant impairment of systolic graft function affecting right, left or both ventricles during HTx or shortly thereafter 2. Severe hemodynamic compromise lasting greater than 1 hour manifested as hypotension (systolic blood pressure <90 mm Hg) and/or low cardiac output (cardiac index <2.2 L/min/m 2 ) requiring !2 intravenous inotropic/pressor drugs, or MCS despite appropriate filling pressures 3. Occurrence within 24 hours after HTx 4. Absence of any other obvious cause of graft dysfunction (hyperacute rejection, severe pulmonary hypertension, massive hemorrhage, and technical problems) Building on this, the International Society for Heart and Lung Transplant (ISHLT) issued a report in 2014 on primary graft dysfunction after HTx. 3 Their classification and definition of severity scale for primary graft dysfunction is presented in Box 2 and Table 2.  PGF is the leading cause of early mortality in HTx, accounting for more than 35% of deaths within 30 days postoperatively. 4 Using the PGF criteria from 2011, a study by the same group looked at the incidence of PGF in a multicenter cohort of 857 heart transplants. 5 The incidence of PGF was 22% with a corresponding early mortality of 53%, compared with 7% in patients without PGF (P 5 .001).

CLINICAL RELEVANCE OF PRIMARY GRAFT DYSFUNCTION IN LUNG TRANSPLANTATION
PGD after lung transplantation describes a clinical syndrome of varying degrees of hypoxemia together with presence of diffuse alveolar infiltrates on chest radiography. In Table 1 Criteria used to assess donor lung suitability, defining a "standard lung donor"  2005 the first ISHLT Working Group on PGD proposed a standardized definition and grading system 6 ( Table 3), and a validation of these definitions was performed in 2016. 7 They described that PGD grade 3 was associated with higher mortality in the acute phase after lung transplantation (PGD grade 3 72 hours post transplant was associated with 30-day mortality relative risk of 6.95 compared with no PGD), and that all grades of PGD were associated with greater risk of bronchiolitis obliterans syndrome development in survivors. The literature supports incidences of PGD of w30% early after transplant and a 15% to 20% incidence of PGD grade 3 at 48 to 72 hours. The time course of PGD progression and resolution has an effect on patient survival outcomes, with patients experiencing severe, persistent PGD having the greatest mortality risk. 8 Table 2 Definition of severity scale for primary graft dysfunction after heart transplantation

PGD in left ventricle (PGD-LV)
Mild PGD-LV: one of the following criteria must be met: It is unequivocal that PGD in heart and lung allografts is an important factor in causing early mortality and morbidity and is also strongly associated with late-onset morbidity. 9 The goal of optimizing heart and lung donor allografts must then be to attenuate or treat the underlying causes of PGD. To achieve this, the mechanisms and timing of injury to heart and lung allografts must be identified.

RISK FACTORS FOR PRIMARY GRAFT DYSFUNCTION IN HEART AND LUNG ALLOGRAFTS
Although specific causes and associations have been linked to an increased risk of developing PGD after heart and lung transplant, similarities between the two exist in that a "multihit" model spanning the entire transplantation process may be envisaged. This multihit model may be seen as a heterogeneous, dynamic accumulation of different injuries incurred at different stages in the transplant process, involving: Donor comorbidity/social history Management of the donor patient The donation procedure Procurement and preservation of the donor organ Organ reperfusion in the recipient Recipient comorbidity Factors in the transplant procedure and postoperative phase A large number of studies have highlighted the association of recipient-related risk factors with the development of PGD in lung transplantation. In a systemic review, the incidence of PGD was shown to be highest in patients with a pretransplant diagnosis of sarcoidosis (50%) or idiopathic pulmonary arterial hypertension (30.3%). 10 One study showed an increased risk of PGD of 30% for every 10 mm Hg increase in mean pretransplant pulmonary artery pressure. 11 Another study found that a combination of increased body mass index, moderate to severe pulmonary arterial hypertension, and a pretransplant diagnosis other than chronic obstructive pulmonary disease or cystic fibrosis could identify recipients at higher risk of PGD at 48 to 72 hours. 12 With respect to donor-related post-lung transplant PGD risk factors, meta-analysis showed that donor cigarette smoking increased PGD risk mainly for "high-risk" recipients 12 while other probable risk factors include an undersized donor relative to the recipient. 8 Another systematic review showed that there was no association of the type of donation procedure, either donation after cardiac death (DCD) or donation after brain death (DBD) with PGD risk. 13 Operative risk factors for PGD are previous pleurodesis in the recipient, 14 use of cardiopulmonary bypass during the procedure, large-volume intraoperative blood product transfusion, and a higher inspired oxygen fraction (FiO 2 ) at the time of donor lung reperfusion. 11 There are numerous recurring donor-, intraoperative-, and recipient-related factors seen in the literature that may be linked to the development of PGD in heart allografts. Major recipient-related factors are linked to increasing age, presence of pulmonary arterial hypertension, and worse pretransplant clinical condition (including dependence on intravenous inotropic support, MCS, and mechanical ventilation). 3 The only validated scoring system for the prediction of PGD after HTx is the RADIAL score, which identified 6 factors with similar weight (risk ratio w2), with 4 recipient-related factors (right atrial pressure >10 mm Hg, Age >60 years, diabetes, inotropic support dependence), 1 related to the donor (age >30 years), and 1 to the procedure (allograft ischemia time >240 minutes). 2 The presence of each of these factors adds 1 point to the total score. The score was validated in a large multicenter cohort showing 3 groups with low (0-1 points), medium (2 points), and high (!3 points) risk for PGD with an actual incidence in each group of 12%, 19%, and 28%, 6 respectively.

CAUSES OF INJURY IN THE DONOR AND DURING THE DONATION PROCEDURE Donation after Brain Death
In a donation procedure following DBD, organs are perfused and ventilated with oxygenated blood up until the moment of procurement. Despite this, DBD donor organs may suffer significant injury from numerous insults, including iatrogenic insults (eg, excessive fluid resuscitation or suboptimal ventilation) and injury incurred secondary to processes inherent in brain death. Brain death is associated with a series of events including intense release of myocardial norepinephrine, resulting in massive mitochondrial calcium overload. 15,16 This in turn may activate myocardial apoptosis or necrosis. Furthermore, a catecholamine storm also causes the activation of multiple proinflammatory mediators, 17 leading to numerous sequelae, including injury to lung epithelium and disruption of the capillary-alveolar membrane causing ("neurogenic") lung edema and acute lung injury.

Donation after Determination of Cardiac Death
Uniform agreement on DCD donor candidacy includes ventilator-dependent individuals with nonrecoverable or irreversible neurologic injury not meeting brain death criteria. Such DCD donors, awaiting cardiac death in a controlled (typically intensive care unit [ICU]) setting, are denoted as "Maastricht category III" donors (with categories I, II, IV, and V being in "uncontrolled" settings 18 ). After the withdrawal of lifesustaining therapy (WLST) in these donors, functional warm ischemia time (WIT) starts when the hemodynamic status reaches critical levels for satisfactory organ perfusion, denoted by a systolic pressure of 50 mm Hg. After the cessation of circulation (cardiopulmonary arrest), a locally determined "no-touch" time interval, typically 5 minutes, will ensue after which verification of death is performed, and the donation procedure may begin. The end of the WIT is denoted by the start of the cold preservation flush in the donor organ. DCD donor organs inevitably suffer hypoxia and hypoperfusion during progression to circulatory arrest and the "no-touch" period of warm, pulseless ischemia. Despite this, and because lungs may be able to better tolerate warm ischemia owing to low metabolic needs and localized storage of oxygen trapped in alveoli, evidence shows that lung allografts show acceptable outcomes after DCD procedures. The 2015 ISHLT DCD Registry Report compared DCD and matched DBD lung transplants and observed a comparable 5-year survival in both groups. 19

TARGETS FOR OPTIMIZATION OF HEART AND LUNG ALLOGRAFTS IN THE DONOR
Management of both DBD and DCD donors to optimize cardiac and pulmonary function and to limit organ injury in the donor milieu requires hemodynamic, neuroendocrine, and organ-specific approaches. Table 4 outlines the standard therapies available to optimize allograft function in the donor. 20 In 2009, a multicenter randomized controlled trial comparing a lung protective ventilation (LPV) strategy with conventional ventilation strategies in DBD donors showed that an LPV strategy improved the preharvest PaO 2 /FiO 2 ratio in comparison with conventional ventilation practices. 21,22 The recommended ventilation strategy for donors ( Table 5) 23 suggests that appropriate LPV plays an important role in attenuating lung injury and optimizing donor lungs.

CAUSES OF INJURY DURING ALLOGRAFT PRESERVATION: STATIC COLD STORAGE
Traditionally, heart and lung allografts are preserved after the initiation of hypothermic (and in the case of heart allografts, cardioplegic) arrest of cell function by static cold storage. This involves the rapid flushing and cooling of the organ with an adapted crystalloid-based fluid, which optimally confers the following protection of the organ: Prevents expansion of the extracellular space by optimizing oncotic pressure Prevents injury from oxygen free radicals Prevents reperfusion damage caused by depletion of ATP stores Static cold storage limits the storage time to a maximum of 4 to 6 hours in heart allografts and approximately 6 to 10 hours in lung allografts. In an ISHLT registry report examining the relationship between outcome of HTx and ischemia time of the allograft, 4 an allograft ischemia time of less than 4 hours was associated with considerably higher survival than an allograft ischemia time of !4 hours. 4,24 Heart allografts exposed to longer periods of cold ischemia have been shown to confer worse survival in the years post transplant when compared with hearts subjected to shorter cold storage times (Fig. 5).

Minimizes hypothermia-induced cell injury Buffers intracellular acidosis
Lung allografts can survive better for longer in cold storage owing to the presence of small stores of oxygen trapped in the alveoli when lungs are preserved in a Abbreviations: IBW, ideal body weight; PEEP, positive end-expiratory pressure; SpO 2 , oxygen saturation by pulse oximetry.  semi-inflated state. However, longer ischemia times are associated with poorer 30day survival post transplant 1 (Fig. 6).
This time limit of effectiveness of cold storage geographically confines the donor pool available to a specific recipient, and is also a serious clinical problem if surgical preparation in the recipient is complex and reperfusion of the allograft is delayed. Examples of this are redo sternotomies in heart transplant recipients (eg, explantation of MCS) or pneumonectomy following pleurodesis in lung transplantation.
It is therefore necessary to develop ways of extending the time allografts can be safely preserved. However, other questions also drive the development of alternative methods of allograft preservation: Are there ways of functionally assessing allografts in an ex vivo setting? Are there techniques available to better preserve and treat allografts to attenuate injury and improve function following implantation?

ALTERNATIVES TO COLD STORAGE ORGAN PRESERVATION Preservation of Heart Allografts
The feasible alternatives to static cold storage confer differing potential advantages. First, continuous or repetitive cold perfusion of heart allografts during preservation allows one to extend the preservation time. In an experimental porcine model, donor hearts preserved for 24 hours were transplanted and showed acceptable function. 25 The second alternative is to preserve heart allografts in a functioning, warm state. 26 Fig. 7). This facilitated a prospective, randomized, noninferiority trial (PROCEED II trial) 27 comparing standard cold cardioplegic storage of human donor hearts with beating-heart allografts perfused and preserved ex vivo at normothermia with the OCS. In the standard group, the cold ischemia In the OCS group, the cold ischemia time was 113 minutes with a 30-day patient and graft survival of 94% (n 5 63) (P 5 .45). Rates of cardiac-related adverse events, incidence of severe rejection, and length of ICU stay did not differ significantly between the groups.

A platform for ex vivo heart perfusion (EVHP) has been developed and is in clinical use (Organ Care System [OCS]; Transmedics,
The opportunity to limit the cold storage time and to biochemically functionally assess donor hearts on the OCS has emboldened the use of "extended criteria" heart allografts in HTx. A single-center experience described the use of EVHP in high-risk heart transplant procedures, 28 defining high risk as either donor-related factors (estimated ischemic time >4 hours, left ventricular ejection fraction [LVEF] <50%, left ventricular hypertrophy, donor cardiac arrest, alcohol/drug abuse, and coronary artery disease) or recipient factors (MCS, elevated pulmonary vascular resistance, or both). Thirty hearts were preserved with the OCS, of which 26 were transplanted. Only one death was observed within the first year, with the remaining 25 patients demonstrating a well-preserved biventricular allograft function (LVEF of 66.3% AE 5.6%, mean longitudinal right ventricular systolic function of 13.6 AE 3.1 mm). This result demonstrates the role EVHP can play in optimizing outcome in "high-risk" heart transplant procedures, possibly by attenuating injury in "extended criteria" allografts, and allows investigators to explore the possibility of using heart allografts from DCD donors.
Traditionally, heart allografts from DCD donors have been considered unsuitable for transplantation because of the warm ischemia to which the allografts are exposed. The period between the withdrawal of life support and organ harvesting subjects the heart allografts to multiple injuries, including hypoxia, hypoperfusion, and ventricular distension. One study investigated the role of EVHP in DCD HTx in a porcine model looking at DCD hearts exposed to 30 minutes of warm ischemia, which were then preserved with either 4 hours of EVHP or 4 hours of standard cold storage. 29 Five of 6 hearts in the EVHP group displayed favorable lactate profiles during EVHP and were successfully weaned off cardiopulmonary bypass. All hearts transplanted from the cold storage group demonstrated acute severe PGD and could not be weaned. This beneficial role of EVHP in DCD heart allografts is thought to be linked to the restoration of perfusion enabling the return of aerobic cell metabolism and replenishment of cellular nutrients. This prevents ongoing ischemic injury and the reperfusion injury that follows.
In a study in humans comparing the outcome after HTx from DCD and DBD donors, 30 EVHP was used for normothermic preservation, transport, and biochemical assessment in all DCD hearts. DCD heart retrieval used one of two differing techniques: normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP). NRP describes a technique whereby perfusion is restored to the arrested heart while still in situ (with exclusion of the cerebral circulation). This approach enables post-warm-ischemia functional assessment of the heart in the donor by pulmonary artery catheter measurements and transesophageal echocardiography. This technique, however, is limited in numerous countries by ethical objection to the restoration of circulation in a deceased donor. The alternative to NRP is DPP, whereby the heart is removed directly after flush with a cold cardioplegia solution and installed and reperfused on EVHP. In DPP, functional assessment of the DCD heart is not possible and, therefore, levels of biomarkers in the EVHP perfusate are used to reflect allograft viability. The study was a single-center observational matched cohort study to compare patients who received transplants of DCD donor hearts with matched recipients who received transplants of DBD donor hearts. Twenty-eight DCD heart transplants were performed with almost equal numbers of DCD hearts procured by either NRP or DPP. Survival at 90 days (DCD 92%, DBD 96%, P 5 1.0), hospital length of stay, allograft function, and 1-year survival (DCD 86%, DBD 88%, P 5 .98) were comparable between groups. The retrieval method (NRP vs DPP) was not associated with a difference in outcome. Early cardiac output was, however, better in the DCD group (2.5 vs 2.0 L/min/m 2 , P 5 .04), possibly explained by the avoidance of myocardial injury caused by the catecholamine storm during brain death in DBD donors and/ or a possible effect of ischemic preconditioning after WLST in DCD donors.

Developments and Controversies in Ex Vivo Heart Perfusion
At present, clinical assessment of the allograft during EVHP relies on sampling lactate levels from the aortic root and pulmonary artery cannulas, using lactate trends as a surrogate for myocardial viability. Other biomarkers of myocardial injury, such a troponin, are of limited use 31 given their elevation caused by nonspecific stresses during donation procedures. Currently there are no modalities to functionally assess heart allografts on EVHP, primarily as it is not possible to fully load and challenge a heart allograft on the OCS platform. Alternative platforms aiming to preserve heart allografts in a beating state while assessing function using pressure-volume loops generated under clinical loading conditions are being investigated.
Myocardial edema has been identified as an issue associated with prolonged preservation of heart allografts on EVHP, although it is uncertain whether the weight gain of the allograft translates to adverse outcomes. 31 To attenuate myocardial edema, alternatives to the current perfusion solution and technique are being explored, aiming to optimize the oncotic pressures of the perfusion fluid and attempting to improve diastolic coronary perfusion while limiting excessive aortic root pressures. 32

ALTERNATIVES TO COLD STORAGE ORGAN PRESERVATION Preservation of Lung Allografts
Cold storage is an acceptable method of preserving donor lungs provided that minimal injury has been incurred in the donor and that the ischemia times are not excessively long. There are, however, techniques offering alternatives to static cold storage, which have come through several noninferiority trials 33,34 and which play vital roles in the use of marginal lung allografts.
The techniques make use of ex vivo lung perfusion (EVLP) technology enabling the perfusion, rewarming, and ventilation of donor lungs in a controlled setting. The first EVLP technique (Lund protocol) was originally designed with the intent of shortterm evaluation of DCD lungs ex vivo 35 :

Lund protocol
Open left atrium Perfusate with type-matched red blood cells Performed on a static protocol-specific integrated system (Vivoline, XVIVO).
In 2016 a single-center study compared the short-term and long-term outcomes of recipients transplanted with initially rejected-for-transplant lungs that were then subjected to EVLP using the Lund protocol (n 5 27) with recipients of non-EVLP (standard) lungs (n 5 145) during the same period. There was no significant difference between short-term and long-term outcomes between the 2 groups. 36 To achieve stable ex vivo perfusion of lungs for periods of up to 12 hours, the Toronto group developed several lung-protective strategies as additions to the Lund protocol, 37,38 including reducing the flow through the lungs from 100% of the predicted cardiac output to 40% with the aim of reducing the incidence of hydrostatic lung edema: Toronto protocol (Fig. 8) Acellular perfusate Closed left atrium Performed on a static system encompassing equipment consisting of either individual parts or integrated in one unit (XPS perfusion system, XVIVO) Furthermore, they preserved the left atrium in a closed state, facilitating maintenance of a positive left atrial pressure of 3 to 5 mm Hg during EVLP. This approach Braithwaite & van der Kaaij was designed to tent open postcapillary venules in the lung and thus prevent their cyclical collapse, which occurs during ventilation. This adaptation was based on studies showing that absence of positive left atrial pressure can lead to unstable alveolar geometry 39 and a reduction in lung compliance. 40 The group published their first major study in 2011, 41 demonstrating that the incidence of PGD in high-risk donor lungs subjected to 4 hours of EVLP was comparable with that of conventional lung allografts (EVLP group n 5 20 vs conventional lung group n 5 116, incidence PGD III 15% vs 30% in the control group, P 5 .11). On the background of these positive clinical results, Slama and colleagues 34 investigated whether EVLP would affect or improve outcome when used for "standard" lung allografts. In a single-center trial, 41 standard lungs in a conventional (non-EVLP) group were compared with 39 standard lungs subjected to 4 hours of EVLP before transplantation. Although shortterm clinical outcomes did not differ between the groups, the incidence of PGD (grade >1) was lower in the EVLP group at all time points compared with the control group (24 hours: 5.7% vs 19.5%, P 5 .10).
An alternative EVLP technique puts emphasis on reducing the cold ischemia time of lung allografts. A mobile EVLP unit (OCS system, Transmedics) has been developed to be taken to lung procurement procedures:

OCS protocol
Open left atrium Perfusate with type-matched red blood cells Portable equipment designed to be taken to the donor hospital and run during the transport of donor lungs After cold flush, donor lungs are installed on the EVLP unit, perfused, rewarmed, and ventilated. The lungs are then kept on the EVLP for normothermic perfusion during transport and preservation for up to 5 hours until the lungs are cooled for a short period of cold ischemia to facilitate the surgical implantation procedure. Similar to the study using the Toronto protocol, a multicenter noninferiority, randomized trial 33 (INSPIRE) comparing outcomes of transplant following preservation of standard lungs with either portable EVLP with the OCS (n 5 141) or static cold storage (n 5 165) demonstrated no clear short-term survival benefit from preservation with the OCS. However, there was a notable decrease in PGD in the EVLP arm of the study, with an incidence of PGD grade 3 within 72 hours post transplant of 17.7% in the OCS group and 29.7% in the static cold storage group (P 5 .015).

Developments and Controversies in Ex Vivo Lung Perfusion
A platform providing access to perfusate, substrate obtained by bronchoalveolar lavage, and lung tissue in the context of normothermic, functional preservation of donor lungs is a hugely welcome research tool in understanding the etiology and pathophysiology of donor lung injury.
Further research strategies of interest include the role of (ultra-)protective ventilation strategies of lungs during EVLP to attenuate lung injury and eventual lung-induced biotrauma. Targeted protective ventilation strategies adapted to the individual lung, including concepts of open lung ventilation and prone ventilation, 42 may lead to increased future use of marginal donor lungs (Video 1).
Still to be performed is a direct comparison of the EVLP protocols and platforms, and whether indeed certain platforms confer a clinically relevant optimization of allograft function in the context of specific injuries.

PERIOPERATIVE MANAGEMENT OF LUNG ALLOGRAFTS
Studies have shown that gradual reintroduction of blood flow during the reperfusion phase, over a 10-minute period, can significantly improve graft function. 43 This prevents reperfusion of cold, atelectatic lungs with full normothermic cardiac output, which can lead to epithelial shear stress injury, 44 inflammation, and lung edema.
In accordance with the principles of protective lung ventilation, the ventilation strategy after reperfusion of the lung allograft should maximize the tidal volume to 4 to 6 mL/kg predicted body weight of the donor. This also includes keeping the FiO 2 low during the early reperfusion period (ie, 0.21-0.5). 11 Novel therapies for the optimization of donor lung function and attenuation of PGD are listed in Table 6. One of the most encouraging therapies is the prophylactic use of surfactant in donor lungs. A pilot study in 2017 45 investigated the presence of surfactant proteins in lung allografts and concurrent rate of PGD in the recipient. The results  Abbreviations: BAL, bronchoalveolar lavage; EVLW, extravascular lung water; IRI, ischemia-reperfusion injury; NAC, N-acetylcysteine.

Optimization of Donor Lungs/Hearts
showed that low levels of surfactant protein gene expression in the lung donor before preservation and implantation was linked to the development of PGD grade 3. Other studies showed that donor lungs exposed to endogenous surfactant before retrieval had significantly higher pulmonary function 1 month after transplantation, but that the benefit disappeared by the end of the first post-transplant year. 46 There remains, however, a lack of prospective, randomized studies regarding the use of surfactant in lung allografts and its role in the prevention or treatment of PGD.

PERIOPERATIVE MANAGEMENT OF HEART ALLOGRAFTS
If the factors linked to the development of PGD have been taken into account and, where possible, attenuated, the perioperative management of heart transplant recipients remains mainly supportive, ensuring adequate oxygen delivery to, and perfusion of, the heart allograft combined with optimizing and supporting other organ systems.
In the case of the development of PGD, supportive treatment involves a combination of inotropes and pulmonary vasodilators. 47 If there is no response to escalating medical treatment, early initiation of short-term MCS is warranted. 3

SUMMARY
Injuries sustained by donor heart and lung allografts during the transplantation process are multiple and cumulative. Optimization of allograft function plays an essential role in the short-term and long-term outcome of the recipient in terms of not only mortality and morbidity but also quality of life. Therapeutic targets to prevent or attenuate injury are to be found in the donor, during the preservation process, intraoperatively during transplantation, and in the postoperative management of the recipient. The newest and most promising methods of optimizing donor heart and lung allografts are to be found in alternative preservation strategies, which enable concomitant functional assessment of donor organs and also provide a modality to initiate therapies to treat injured allografts or prevent injury during reperfusion in the recipient.