ABSTRACT Background The epidermal growth factor receptor (EGFR) pathway is involved in kidney tissue repair and growth. Preclinical interventional data and scarce human data have suggested a role for this pathway in the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD), while other data have suggested that its activation is causally linked to repair of damaged kidney tissue. We hypothesize that urinary EGFR ligands, as a reflection of EGFR activity, are associated with kidney function decline in ADPKD in the context of tissue repair following injury, and as the disease progresses as a sign of insufficient repair. Methods In the present study, we measured the EGFR ligands, EGF and heparin binding-EGF (HB-EGF), in 24-h urine samples of 301 ADPKD patients and 72 age- and sex-matched living kidney donors to dissect the role of the EGFR pathway in ADPKD. During a median follow-up of 2.5 years, the association of urinary EGFR ligand excretion with annual change in estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume in ADPKD patients was analyzed using mixed-models methods, and the expression of three closely related EGFR family receptors in ADPKD kidney tissue was investigated by immunohistochemistry. Additionally, the effect of reducing renal mass (after kidney donation), was assessed to investigate whether urinary EGF matches this reduction and thus reflects the amount of remaining healthy kidney tissue. Results At baseline, urinary HB-EGF did not differ between ADPKD patients and healthy controls (P = .6), whereas a lower urinary EGF excretion was observed in ADPKD patients [18.6 (11.8–27.8)] compared with healthy controls [51.0 (34.9–65.4) μg/24 h, P < .001]. Urinary EGF was positively associated with baseline eGFR (R = 0.54, P < .001) and a lower EGF was strongly associated with a more rapid GFR decline, even when adjusted for ADPKD severity markers (β = 1.96, P < .001), whereas HB-EGF was not. Expression of the EGFR, but not other EGFR-related receptors, was observed in renal cysts but was absent in non-ADPKD kidney tissue. Finally, unilateral nephrectomy resulted in a decrease of 46.4 (–63.3 to –17.6) % in urinary EGF excretion, alongside a decrease of 35.2 ± 7.2% in eGFR and 36.8 ± 6.9% in measured GFR (mGFR), whereas maximal mGFR (measured after dopamine induced hyperperfusion) decreased by 46.1 ± 7.8% (all P < .001). Conclusions Our data suggest that lower urinary EGF excretion may be a valuable novel predictor for kidney function decline in patients with ADPKD.

Multiple cases of potentially life-threatening thrombotic microangiopathy (TMA) have resulted from intravenous abuse of medications containing polyethylene oxide (PEO), most often Opana ER (oxymorphone hydrochloride extended release). No validated models are available to assess the risk of TMA with different formulations and extraction methods following intravenous abuse. We have developed an in vitro system that involves passing pooled blood containing the excipient of interest through a syringe needle and assessing haemolysis via haemoglobin release. Haemolysis is induced by high shear stress caused by the flow of blood containing PEO through a narrow-bore syringe needle, recapitulating the mechanism in small blood vessels. Using the in vitro system, we demonstrate that high-molecular-weight PEO (>1 MDa) induces haemolysis in a concentration-dependent manner under flowing but not static conditions. We use data from the in vitro system and published in vivo data to predict the time course of the haemolytic response in vivo via a pharmacometric model. The in vitro system is a novel method for investigating factors influencing PEO-induced haemolysis. In combination with our model-based translational framework, the in vitro system allows straightforward assessment of the haemolytic potential of PEO-containing medications, and may find application in gauging TMA risk following intravenous abuse.

Background: Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. Methods: At baseline, albumin, immunoglobulin G, kidney injury molecule 1, β2 microglobulin (β2MG), heart-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and monocyte chemotactic protein-1 ­(MCP-1) were measured in 24-h urine samples of patients participating in a study investigating the therapeutic efficacy of lanreotide in ADPKD. Individual change in estimated glomerular filtration rate (eGFR) during follow-up was calculated using mixed-model analysis taking into account 13 ­eGFRs (chronic kidney disease EPIdemiology) per patient. Logistic regression analysis was used to select urinary biomarkers that had the best association with rapidly progressive disease. The predictive value of these selected urinary biomarkers was compared to other risk scores using C-statistics. Results: Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m2, and a height-adjusted total kidney volume (htTKV) of 1,082 (736–1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered (n = 152). A stepwise backward analysis revealed that β2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of β2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64–0.82] vs. 0.61 [0.51–0.71], p = 0.04) and comparable to that of the predicting renal outcomes in ­ADPKD score (AUC 0.73 [0.64–0.82] vs. 0.65 [0.55–0.75], p = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. Conclusion: Measurement of urinary β2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or PKD mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.

OBJECTIVETo establish the incidence of massive transfusion and overall transfusion requirements during lung transplantation, changes over time, and association with outcome in relation to patient complexity.DESIGNRetrospective cohort study.SETTINGUniversity hospital.PARTICIPANTSAll 514 adult patients who underwent transplantation from 1990 until 2015.INTERVENTIONSNone.MEASUREMENTS AND MAIN RESULTSPatient records and transfusion data, divided into 5-year intervals, were analyzed. The incidence of massive transfusion (>10 units of red blood cells [RBCs] in 24 h) was 27% and did not change over time, whereas the median (interquartile range) transfusion requirement in the whole cohort decreased from 8 (5-12) to 3 (0-10) RBCs (p < 0.001). In patients transplanted from the intensive care unit, the incidence of massive transfusion increased over time from 25% to 54% (p = 0.04) and median transfusion requirements from 4.5 (3-8.5) units to 14.5 (5-26) units of RBCs (p = 0.03). Multivariable analysis showed that circulatory support, pulmonary hypertension, re-transplantation, cystic fibrosis, Eisenmenger syndrome, bilateral transplantation, and low body mass index were associated with massive transfusion. Patients with massive transfusion had more primary graft dysfunction grade III at 0, 24, 48, and 72 hours (p < 0.001), higher 30-day mortality (13% v 4%; p < 0.001), and lower 5-year survival (hazard ratio 3.67 [95% confidence interval 1.72-7.85]; p < 0.001).CONCLUSIONThe incidence of massive transfusion did not change over time, whereas transfusion requirements in the whole cohort decreased. In patients transplanted from the intensive care unit, massive transfusion and transfusion requirements increased. Massive transfusion was associated with poor outcome.

Abstract During hemocompatibility testing, activation products may reach plateau values which can result in less distinction between hemocompatible and hemo‐incompatible materials. Of concern is an underestimation of the blood activation caused by the biomaterial of interest, which may result in a false assessment of hemocompatibility. To elucidate the optimal incubation time for in vitro hemocompatibility testing, we used the Haemobile circulation model with human whole blood. Blood from healthy volunteers was in vitro incubated under pulsatile flow with physiological wall shear stress conditions at 37°C for 30, 60, 120, or 240 min. Test loops containing low‐density polyethylene and polydimethylsiloxane served as low and high reference materials, that is, hemocompatible and hemo‐incompatible biomaterials, respectively. In addition, empty loops served as a negative reference. Thrombogenicity, platelet function, inflammatory response, coagulation, and hemolysis between references and incubation times were compared. We found that thrombogenicity and platelet function were significantly affected by both the duration of incubation and the type of material. In particular, thrombogenicity and platelet function assessments were affected by incubation time. We found that an exposure time of 60 min was sufficient, and for almost all variables an optimal incubation time to discriminate between the low and high reference material. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2335–2342, 2019.

Haemodialysis (HD) patients suffer from an increased risk of cardiovascular disease (CVD). Skin autofluorescence (SAF) is a strong marker for CVD. SAF indirectly measures tissue advanced glycation end products (AGE) being cumulative metabolites of oxidative stress and cytokine-driven inflammatory reactions. The dialysates often contain glucose.

INTRODUCTION:The variable disease course of autosomal dominant polycystic kidney disease (ADPKD) makes it important to develop biomarkers that can predict disease progression, from a patient perspective and to select patients for renoprotective treatment. We therefore investigated whether easy-to-measure urinary biomarkers are associated with disease progression and have additional value over that of conventional risk markers. METHODS:At baseline, inflammatory, glomerular, and tubular damage markers were measured in 24-hour urine collections (albumin, IgG, kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), β2 microglobulin (β2MG), heart-type fatty acid binding protein (HFABP), macrophage migration inhibitory factor (MIF), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein-1 (MCP-1). Disease progression was expressed as annual change in estimated glomerular filtration rate (eGFR, Chronic Kidney Disease EPIdemiology equation), measured glomerular filtation rate (mGFR, using 125I-iothalamate), or height-adjusted total kidney volume (htTKV). Multivariable linear regression was used to assess associations of these markers independent of conventional risk markers. RESULTS:A total of 104 ADPKD patients were included (40 ± 11 years, 39% female, eGFR 77 ± 30, mGFR 79 ± 30 ml/min per 1.73 m2 and htTKV 852 [510-1244] ml/m). In particular, β2MG and MCP-1 were associated with annual change in eGFR, and remained associated after adjustment for conventional risk markers (standardized β = -0.35, P = 0.001, and standardized β = -0.29, P = 0.009, respectively). Adding β2MG and MCP-1 to a model containing conventional risk markers that explained annual change in eGFR significantly increased the performance of the model (final R2  = 0.152 vs. 0.292, P = 0.001). Essentially similar results were obtained when only patients with an eGFR ≥ 60 ml/min per 1.73 m2 were selected, or when change in mGFR was studied. Associations with change in htTKV were less strong. CONCLUSION:Urinary β2MG and MCP-1 excretion were both associated with GFR decline in ADPKD, and had added value beyond that of conventional risk markers. These markers therefore have the potential to serve as predictive tools for clinical practice.

Hemocompatibility of blood contacting medical devices has to be evaluated before their intended application. To assess hemocompatibility, blood flow models are often used and can either consist of in vivo animal models or in vitro blood flow models. Given the disadvantages of animal models, in vitro blood flow models are an attractive alternative. The in vitro blood flow models available nowadays mostly focus on generating continuous flow instead of generating a pulsatile flow with certain wall shear stress, which has shown to be more relevant in maintaining hemostasis. To address this issue, the authors introduce a blood flow model that is able to generate a pulsatile flow and wall shear stress resembling the physiological situation, which the authors have coined the "Haemobile." The authors have validated the model by performing Doppler flow measurements to calculate velocity profiles and (wall) shear stress profiles. As an example, the authors evaluated the thrombogenicity of two drug eluting stents, one that was already on the market and one that was still under development. After identifying proper conditions resembling the wall shear stress in coronary arteries, the authors compared the stents with each other and often used reference materials. These experiments resulted in high contrast between hemocompatible and incompatible materials, showing the exceptional testing capabilities of the Haemobile. In conclusion, the authors have developed an in vitro blood flow model which is capable of mimicking physiological conditions of blood flow as close as possible. The model is convenient in use and is able to clearly discriminate between hemocompatible and incompatible materials, making it suitable for evaluating the hemocompatible properties of medical devices.

The use of unactivated blood for hemocompatibility testing is essential to obtain reliable results. Here, the authors study the influence of heparinized whole blood storage time and temperature on blood activation and evaluate the importance of initiating hemocompatibility tests within 4 h of blood collection. Blood from healthy volunteers was collected and analyzed with minimal delay, after 30 min and after 60 min of storage at room temperature, 30 or 37 °C. In addition, blood was analyzed after 1, 2, or 4 h of storage at room temperature. Platelet count, mean platelet volume, platelet binding capacity to collagen and thromboxane B2 were measured to assess platelet function, complement complex C5b-9 and elastase were measured to assess activation of the inflammatory response system, and thrombin-antithrombin III was measured to assess activation of the coagulation system. Furthermore, free hemoglobin was measured in platelet poor plasma as an indicator for red blood cell damage. The authors found that storage at 30 °C significantly increased platelet and coagulation activity after 60 min and storage at 37 °C significantly increased platelet, coagulation, and white blood cell activity after 60 min. Storage at room temperature significantly decreased platelet binding to collagen after 4 h and increased platelet activity after 1 h onward and white blood cell activity after 4 h. Their results show that short-term storage of heparinized whole blood significantly influences biomarkers over time, especially at 30 and 37 °C compared to room temperature. However, blood stored at room temperature for 4 h is also affected. In particular, platelet function and white blood cell activity are significantly influenced after 4 h of stationary storage at room temperature; therefore, the authors propose that hemocompatibility tests should be initiated well within 4 h of blood collection, preferably within 2 h.

BACKGROUND AND OBJECTIVESRecent animal experiments suggest that dysregulation of the EGF receptor pathway plays a role in the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD). Research on EGF receptor ligands in humans with ADPKD is lacking. EGF receptor ligands were measured in patients with ADPKD at baseline and after treatment with a vasopressin V2 receptor antagonist (V2RA) because this information might provide a rationale for future V2RA combination therapy.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSBlood and urine concentrations of the EGF receptor ligands heparin-binding (HB)-EGF, EGF, and TGF-α were measured by ELISAs in 27 patients with ADPKD who participated in a single-center study investigating a V2RA in 2011-2013 and in 27 controls who were selected from a general population-based observational study. Cyst fluid concentrations were also measured. In patients with ADPKD, ligands were measured at baseline, after 3-week treatment with a V2RA, and 3 weeks after drug withdrawal. The measured GFR (mGFR) was determined by iothalamate infusion, and total kidney volume was measured by magnetic resonance imaging.RESULTSUrinary HB-EGF excretion and plasma concentration were higher in patients with ADPKD than in controls (median, 1.4 [interquartile range, 1.2-1.9] versus 0.6 [0.4-0.8] µg/24 hours [P<0.001] and 157.9 [83.1-225.9] versus 77.2 [37.2-174.3] pg/ml [P=0.04]). In contrast, urinary EGF excretion and plasma EGF concentration were lower in patients with ADPKD, whereas TGF-α did not differ between patients and controls. Higher HB-EGF excretion was correlated with more severe disease, assessed as lower mGFR (r=-0.39; P=0.05), higher total kidney volume (r=0.39; P=0.05), and higher urinary excretion of albumin and heart-type fatty acid-binding protein, whereas higher EGF excretion and TGF-α excretion were negatively correlated with disease severity. During V2RA treatment, HB-EGF excretion increased (from 1.4 [1.2-1.9] to 2.4 [2.1-3.1] µg/24 hours; P<0.001).CONCLUSIONIn patients with ADPKD, higher urinary HB-EGF excretion is correlated with more severe disease. Whether this association is causal needs to be investigated in intervention studies.

Diagnosis of pulmonary dysfunction is currently almost entirely based on a vast series of physiological changes, but comprehensive research is focused on determining biomarkers for early diagnosis of pulmonary dysfunction. Here we discuss the use of biomarkers of lung injury in cardiothoracic surgery and their ability to detect subtle pulmonary dysfunction in the perioperative period. Degranulation products of neutrophils are often used as biomarker since they have detrimental effects on the pulmonary tissue by themselves. However, these substances are not lung specific. Lung epithelium specific proteins offer more specificity and slowly find their way into clinical studies.

Background A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR. Study Design Clinical trial with comparisons before and after treatment. Setting & Participants Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting. Intervention Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively). Outcomes Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers). Measurements GFR was measured by 125I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression. Results In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron. Limitations Limited sample size, no control group. Conclusions In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with lower GFRs might benefit from long-term treatment with tolvaptan, as has been observed for patients with preserved GFRs.

OBJECTIVESIn addition to its blood-sparing effects, intraoperative cell salvage may reduce lung injury following cardiac surgery by removing cytokines, neutrophilic proteases and lipids that are present in cardiotomy suction blood. To test this hypothesis, we performed serial measurements of biomarkers of the integrity of the alveolar-capillary membrane, leucocyte activation and general inflammation. We assessed lung injury clinically by the duration of postoperative mechanical ventilation and the alveolar arterial oxygen gradient.METHODSSerial measurements of systemic plasma concentrations of interleukin-6 (IL-6), myeloperoxidase, elastase, surfactant protein D (SP-D), Clara cell 16 kD protein (CC16) and soluble receptor for advanced glycation endproducts (sRAGEs) were performed on blood samples from 195 patients who underwent cardiac surgery with the use of a cell salvage (CS) device (CS, n = 99) or without (CONTROL, n = 96).RESULTSPostoperative mechanical ventilation time was shorter in the CS group than in the CONTROL group [10 (8-15) vs 12 (9-18) h, respectively, P = 0.047]. The postoperative alveolar arterial oxygen gradient, however, was not different between groups. After surgery, the lung injury biomarkers CC16 and sRAGEs were lower in the CS group than in the CONTROL group. Biomarkers of systemic inflammation (IL-6, myeloperoxidase and elastase) were also lower in the CS group. Finally, mechanical ventilation time correlated with CC16 plasma concentrations.CONCLUSIONSThe intraoperative use of a cell salvage device resulted in less lung injury in patients after cardiac surgery as assessed by lower concentrations of lung injury markers and shorter mechanical ventilation times.

Background Tissue advanced glycation end products (AGE) are increased in hemodialysis (HD) patients, especially those with cardiovascular complications. Skin autofluorescence (skin-AF) can noninvasively estimate the accumulation of AGE in tissue. The aim was to clarify whether HD using a high-flux (HF) dialyzer favors plasma- or skin-AF removal compared to low-flux (LF) dialysis. Material and methods 28 patients were treated with either an HF-HD or LF-HD but otherwise unchanged conditions in a cross-over design. A glucose containing dialysate was used. Skin-AF was measured noninvasively with an AGE reader before and after HD. Fluorescence (370 nm/465 nm) of plasma (p-AF) was determined as total and nonprotein-bound fractions. Correction for hemoconcentrations were made using the change in serum albumin. Paired and nonpaired statistical analyses were used. Results Skin-AF was unchanged after LF- and HF-dialysis. Total, free, and protein- bound p-AF was reduced after a single LF-HD by 21%, 28%, and 17%, respectively (P<.001). After HF HD total and free p-AF was reduced by 5% and 15%, respectively (P<.001), while protein bound values were unchanged. The LF-HD resulted in a more pronounced reduction of p-AF than did HF HD (P<.001). Serum albumin correlated inversely with p-AF in HF-HD. Conclusions In the dialysis settings used there was no significant change in skin AF after dialysis, with LF or with HF dialysis. Although only limited reduction in plasma fluorescence was observed, this was more pronounced when performing LF dialysis. These data are not in overwhelming support of the use of HF dialysis in the setting used in this study.

PURPOSE:Cardiopulmonary bypass is still a major cause of lung injury and delay in pulmonary recovery after cardiac surgery. Although it has been shown that pulsatile flow induced by intra-aortic balloon pumping is beneficial for preserving lung function, it is not clear if the same beneficial effect can be accomplished with pulsatile flow generated in the extracorporeal circuit. Therefore, we investigated the effect of pulsatile flow, produced by a centrifugal pump, on lung function in elderly patients.METHODS:Serial measurements of lung biomarkers Clara cell 16 kD protein, surfactant protein D, and elastase were performed on blood samples from 37 elderly patients (≥75 years) who underwent elective aortic valve replacement surgery with CPB, either with pulsatile perfusion or continuous perfusion. Pulmonary function was assessed by postoperative ventilation time, the arterial blood oxygenation (PaO2/FiO2), the alveolar-arterial oxygen gradient (Aa-O2 gradient) and the pulmonary vascular resistance indexed by body surface area (PVRi).RESULTS:There was no difference in lung function between both groups, as assessed by the postoperative ventilation time, the PaO2/FiO2 ratio, and the Aa-O2 gradient. The PVRi, however, was significantly lower in the pulsatile perfusion group 15 mins after the administration of protamine (p<0.05). The plasma concentrations of the lung biomarkers increased during surgery and peaked at 1 h ICU, there were however no differences between groups.CONCLUSIONS:Pulsatile flow does not seem beneficial to postoperative lung function in elderly patients. Moreover, pulsatile flow does not affect lung function on a subclinical level as assessed by lung biomarkers.

Background: Despite continuous improvements in materials and perfusion techniques, cardiac surgery still causes lung injury and a delay of pulmonary recovery. Currently, there is no gold standard for quantifying cardiac surgery induced lung injury and dysfunction. Adding objective measures, such as plasma biomarkers, could be of great use here. In this study the utility of lung epithelium specific proteins as biomarkers for lung dysfunction was evaluated.Methods: Serial measurements of plasma concentrations of Clara cell 16 kD (CC16) protein, Surfactant protein D (SP-D), Elastase and Myeloperoxidase were performed on blood samples from 40 patients who underwent coronary artery bypass grafting with cardiopulmonary bypass (CABG, n = 20) or without cardiopulmonary bypass (OPCAB, n = 20).Results: The increase of SP-D and CC16 between pre-operative concentrations and concentrations at the end of cardiopulmonary bypass, correlated with the Aa-O-2 gradient at 1 hour on the ICU (R-s = 0.409, p = .016 and R-s = 0.343, p = .043, respectively). Furthermore, SP-D and CC16 were higher in CABG than in OPCAB at the end of surgery [8.96 vs. 4.91 ng/mL, p = .042 and 92 vs. 113%, p = .007, respectively]. After 24 h both biomarkers returned to their baseline values.Conclusions: Our results show that increases in plasma of SP-D and CC16 correlate with clinical lung injury after coronary artery bypass surgery. Therefore, lung epithelium specific proteins seem to be a useful biomarker for measuring lung injury in the setting of cardiac surgery.

Donations after circulatory death (DCD) lung grafts are an alternative to extend the donor pool in lung transplantation. This study investigates the use of an in situ lung perfusion system (ISLP) in the donor to evaluate category I–II lungs. Pigs were sacrificed by ventricular fibrillation. All animals underwent 20 min of cardiopulmonary resuscitation and 5 min hands‐off period after which heparin was administered. In group [WI‐1], this was followed by 1 h of warm ischemia (WI) and 2 h of topical cooling (TC). In group [WI‐2], 2 h of WI was followed by 1 h of TC. In group [WI‐0], there was a minimal period of WI and no TC. In all three groups, the lungs were then evaluated during 60 min with ISLP. [WI‐0] lungs showed a significantly higher compliance and Δ PO2/FiO2 compared with [WI‐1] and [WI‐2]. PaCO2 and lactate production were higher in [WI‐2] versus [WI‐0]. Wet/Dry weight ratio was significantly higher in [WI‐2] compared with [WI‐0] in two lung biopsy locations. A high W/D weight ratio was correlated with a lower compliance, higher lactate production, and a higher PaCO2. ISLP is an effective way to assess the quality of lungs from category I–II DCD donors.