Search Results (16)

Lung transplantation remains the standard of care for end-stage lung disease, yet a persistent gap exists between donor lung availability and growing clinical demand. Expanding the donor pool and optimising donor lung management are therefore critical priorities. However, no universally accepted management protocols are currently in place. This narrative review examines evidence-based strategies to improve lung utilisation across three donor categories: donors after brain death (DBD), controlled donors after circulatory death (cDCD), and uncontrolled donors after circulatory death (uDCD). A systematic literature search was conducted to identify interventions targeting lung preservation and function, including protective ventilation, recruitment manoeuvres, fluid and hormonal management, and ex vivo lung perfusion (EVLP). Distinct pathophysiological mechanisms—sympathetic storm and systemic inflammation in DBD, ischaemia–reperfusion injury in cDCD, and prolonged warm ischaemia in uDCD—necessitate tailored approaches to lung preservation. In DBD donors, early application of protective ventilation, bronchoscopy, and infection surveillance is essential. cDCD donors benefit from optimised pre- and post-withdrawal management to mitigate lung injury. uDCD donor lungs, uniquely vulnerable to ischaemia, require meticulous post-mortem evaluation and preservation using EVLP. Implementing structured, evidence-based lung management strategies can significantly enhance donor lung utilisation and expand the transplantable organ pool. The integration of such practices into clinical protocols is vital to addressing the global shortage of suitable lungs for transplantation. Full article

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. It can cause blockage of the airways, leading to breathlessness and lung failure. Here, we used a ventilatory setup to demonstrate the effect of BromAc^® in dissolving mucus plugs in a novel ex vivo ovine obstructive lung model. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc^®, and saline control were administered via an Aerogen^® vibrating nebulizer and ventilated for 30 or 60 min. Ventilatory recording of resistance, compliance, and tidal volume was conducted, and rheology pre- and post-treatment were measured. A significant decline in airway resistance (p < 0.0001) compared to the saline control was observed when treated with Bromelain, Ac, and BromAc^®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter time points (p < 0.05) at lower doses of the drugs. Changes in compliance, peak pressure, and tidal volume were not observed after administration of the drugs. Rheology measurements revealed that BromAc^®TM significantly reduced the viscosity of the mucin at the end of 30 min and 60 min time points (p < 0.001) compared to the saline control. BromAc^® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex vivo ovine model. Full article

Herein, commercially available MOS gas sensors running in temperature cycling operations are studied for the online monitoring of propofol in an ex vivo ventilation and perfusion lung model. A porcine lung was connected to a heart–lung machine and propofol was added into the blood reservoir. The MOS sensor was able to quantitatively detect exhaled propofol in the very low ppb range. The results are in accordance with those obtained by a propofol-sensitive ion mobility spectrometer. Full article

Volatile anesthetics have been shown in different studies to reduce ischemia reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) facilitates graft evaluation, extends preservation time and potentially enables injury repair and improvement of lung quality. We hypothesized that ventilating lungs with sevoflurane during EVLP would reduce lung injury and improve lung function. We performed a pilot study to test this hypothesis in a slaughterhouse sheep DCD model. Lungs were harvested, flushed and stored on ice for 3 h, after which EVLP was performed for 4 h. Lungs were ventilated with either an FiO₂ of 0.4 (EVLP, n = 5) or FiO₂ of 0.4 plus sevoflurane at a 2% end-tidal concentration (C_et) (S-EVLP, n = 5). Perfusate, tissue samples and functional measurements were collected and analyzed. A steady state of the target C_et sevoflurane was reached with measurable concentrations in perfusate. Lungs in the S-EVLP group showed significantly better dynamic lung compliance than those in the EVLP group (p = 0.003). Oxygenation capacity was not different in treated lungs for delta partial oxygen pressure (PO₂; +3.8 (−4.9/11.1) vs. −11.7 (−12.0/−3.2) kPa, p = 0.151), but there was a trend of a better PO₂/FiO₂ ratio (p = 0.054). Perfusate ASAT levels in S-EVLP were significantly reduced compared to the control group (198.1 ± 93.66 vs. 223.9 ± 105.7 IU/L, p = 0.02). We conclude that ventilating lungs with sevoflurane during EVLP is feasible and could be useful to improve graft function. Full article

Uncontrolled donation after circulatory death (uDCD) represents a potential source of lungs, and since Steen’s 2001 landmark case in Sweden, lungs have been recovered from uDCD donors and transplanted to patients in other European countries (France, the Netherlands, Spain and Italy) with promising results. Disparities still exist among European countries and among regions in Italy due to logistical and organizational factors. The present manuscript focuses on the clinical experiences pertaining to uDCD lungs in North America and European countries and on different lung maintenance methods. Existing experiences (and protocols) are not uniform, especially with respect to the type of lung maintenance, the definition of warm ischemic time (WIT) and, finally, the use of ex vivo perfusion (available in the last several years in most centers). In situ lung cooling may be superior to protective ventilation, but this process may be difficult to perform in the uDCD setting and is also time-consuming. On the other hand, the “protective ventilation technique” is simpler and feasible in every hospital. It may lead to a broader use of uDCD lung donors. To date, the results of lung transplants performed after protective ventilation as a preservation technique are scarce but promising. All the protocols comprise, among the inclusion criteria, a witnessed cardiac arrest. The detectable differences included preservation time (240 vs. 180 min) and donor age (<55 years in Spanish protocols and <65 years in Toronto protocols). Overall, independently of the differences in protocols, lungs from uDCD donors show promising results, and the possibility of optimizing ex vivo lung perfusion may broaden the use of these organs. Full article

Methylglyoxal (MG) is a known highly reactive dicarbonyl and precursor to free radicals and advanced glycation end-products (AGEs). It is discussed to be involved in tissue aging and in the pathogenesis of different degenerative diseases. The effect of long-term oral administration of MG, simulating dietary MG intake, on the lung biomechanics of wild type (WT) and receptor for advanced glycation end-products knockout (RAGE-KO) mice was studied using an ex vivo ventilation system starting at the age of 6 months and after feeding for 6 and 12 months with MG. Our results showed that MG was taken up in the circulation and efficiently excreted with urine. The amount of free urinary MG measured after 12 months of feeding was lowered. After 12 months feeding, a significant airway resistance increase accompanied by a decrease of the maximal inspiratory airflow was observed in WT animals. No effect of MG in lung function of RAGE-KO mice could be detected. Despite the evidence that MG entered the systemic circulation, no MG-derived AGE accumulation was detected in the lung lysates in dependency on MG-feeding. Our data indicate that the short-term feeding of MG has little effect in vivo. Only after long-term treatment was MG secretion reduced, leading to tissue impairment. Full article

In pediatric liver transplantation (pLT), the risk for the manifestation and relevance of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) is high. This observational study aimed to evaluate the incidence, relevance and risk factors for IAH and ACS by monitoring the intra-abdominal pressure (IAP), macro- and microcirculation (near-infrared spectroscopy (NIRS)), clinical and laboratory status and outcomes of 27 patients (16 female) after pLT (median age at pLT 35 months). Of the patients, 85% developed an elevated IAP, most of them mild. However, 17% achieved IAH° 3, 13% achieved IAH° 4 and 63% developed ACS. A multiple linear regression analysis identified aortal hepatic artery anastomosis and cold ischemia time (CIT) as risk factors for increased IAP and longer CIT and staged abdominal wall closure for ACS. ACS patients had significantly longer mechanical ventilation (p = 0.004) and LOS-PICU (p = 0.003). No significant correlation between NIRS or biliary complications and IAH or ACS could be shown. IAH and ACS after pLT were frequent. NIRS or grade of IAH alone should not be used for monitoring. A longer CIT is an important risk factor for higher IAP and ACS. Therefore, approaches such as the ex vivo machine perfusion of donor organs, reducing CIT effects on them, have great potential. Our study provides important basics for studying such approaches. Full article

Objective: Current treatments for blast-induced lung injury are limited to supportive procedures including mechanical ventilation. The study aimed to investigate the role of post-trauma-induced oedema generation in the function of time and trauma intensity and the probable role of beta 2-adrenergic receptors (β₂-ARs) agonists on pulmonary oedema. The study is conducted using an ex vivo model after an experimental in vivo blast-induced thorax trauma in rats. Methods: Rats were randomised and divided into two groups, blast and sham. The blast group were anaesthetised and exposed to the blast wave (3.16 ± 0.43 bar) at a distance of 3.5 cm from the thorax level. The rats were sacrificed 10 min after the blast, the lungs explanted and treated with terbutaline, formoterol, propranolol or amiloride to assess the involvement of sodium transport. Other groups of rats were exposed to distances of 5 and 7 cm from the thorax to reduce the intensity of the injury. Further, one group of rats was studied after 180 min and one after 360 min after a 3.5 cm blast injury. Sham controls were exposed to identical procedures except for receiving blast overpressure. Results: Lung injury and oedema generation depended on time after injury and injury intensity. Perfusion with amiloride resulted in a further increase in oedema formation as indicated by weight gain (p < 0.001), diminished tidal volume (Tv) (p < 0.001), and increased airway resistance (p < 0.001). Formoterol caused a significant increase in the Tv (p < 0.001) and a significant decrease in the airway resistance (p < 0.01), while the lung weight was not influenced. Trauma-related oedema was significantly reduced by terbutaline in terms of lung weight gain (p < 0.01), Tv (p < 0.001), and airway resistance (p < 0.01) compared to control blast-injured lungs. Terbutaline-induced effects were completely blocked by the β-receptor antagonist propranolol (p < 0.05). Similarly, amiloride, which was added to terbutaline perfusion, reversed terbutaline-induced weight gain reduction (p < 0.05). Conclusions: β₂-adrenoceptor stimulation had a beneficial impact by amiloride-dependent sodium and therefore, fluid transport mechanisms on the short-term ex vivo oedema generation in a trauma-induced in vivo lung injury of rats. Full article

Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors. Isolated perfused mouse lungs (IPLs) were perfused and ventilated for 270 min. Lungs were instilled with saline solution (control), welding fume particle suspension (WFs) or the soluble fraction of the welding fumes (SF-WFs). Bronchoalveolar lavage fluid (BALF) and perfusate samples were analyzed for cytokine levels and lung tissue mRNA expression levels were analyzed via RT-PCR. All lungs instilled with WFs did not complete the experiments due to a fatal reduction in tidal volume. Accordingly, IL-6 and MPO levels were significantly higher in BALF of WF lungs compared to the control. IL-6 and MPO mRNA expression levels were also increased for WFs. Lungs instilled with SF-WFs only showed mild reactions in tidal volume, with BALF and mRNA expression levels not significantly differing from the control. Zinc- and copper-containing welding fume particles adversely affect IPLs when instilled, as evidenced by the fatal loss in tidal volume and increased cytokine expression and secretion. The effects are mainly caused by the particles, not by the soluble fraction. Full article

Otitis media is often connected to Eustachian tube dysfunction (ETD). Until now, there was no large animal model available for the examination of new treatment methods such as stents for the Eustachian tube (ET). Thus, the aim of the study was to develop a method to reproducibly induce ETD by injection of fillers and without permanent closure of the ET. Tools for safe injection of hyaluronic acid (HA) in the surrounding of the ET were developed. In ex vivo experiments, HA mixed with Imeron^® was injected close to the nasopharyngeal orifice of the ET of blackface sheep. The established depot was visualized using cone beam computer tomography and magnetic resonance imaging, and stents could be placed into the ET. A reliable position of the HA depot was achieved. This method was transferred to in vivo, and middle ear ventilation was investigated by tympanometry. ETD was achieved with amounts of 2.5 mL HA or higher. None of the animals showed any sign of discomfort or complications. The induced ETD lasted for 3 to 13 (maximum observation period) weeks and was also combined with middle ear effusion. A model of ETD based on injection of HA next to the ET was successfully established and is now available to test novel treatment options for ET functionality. Full article

The acceptable duration of donor warm ischemia time (DWIT) after cardiocirculatory death (DCD) is still debated. We analyzed the biomolecular profile and function during ex vivo lung perfusion (EVLP) of DCD lungs and their correlation with lung transplantation (LuTx) outcomes. Donor data, procurement times, recipient outcomes, and graft function up to 1 year after LuTx were collected. During EVLP, the parameters of graft function and metabolism, perfusate samples to quantify inflammation, glycocalyx breakdown products, coagulation, and endothelial activation markers were obtained. Data were compared to a cohort of extended-criteria donors after brain death (EC-DBD). Eight DBD and seven DCD grafts transplanted after EVLP were analyzed. DCD’s DWIT was 201 [188;247] minutes. Donors differed only regarding the duration of mechanical ventilation that was longer in the EC-DBD group. No difference was observed in lung graft function during EVLP. At reperfusion, “wash-out” of inflammatory cells and microthrombi was predominant in DCD grafts. Perfusate biomolecular profile demonstrated marked endothelial activation, characterized by the presence of inflammatory mediators and glycocalyx breakdown products both in DCD and EC-DBD grafts. Early graft function after LuTx was similar between DCD and EC-DBD. DCD lungs exposed to prolonged DWIT represent a potential resource for donation if properly preserved and evaluated. Full article

Objective: Ex vivo organ perfusion is an advanced preservation technique that allows graft assessment and extended ex situ intervals. We hypothesized that its properties might be especially beneficial for high-risk recipients and/or donors with extended criteria. Methods: We reviewed the outcomes of 119 consecutive heart transplant patients, which were divided into two groups: A (OCS) vs. B (conventional). Ex vivo organ perfusion was performed using the Organ Care System (OCS). Indications for OCS-usage were expected ischemic time of >4 h or >2 h plus given extended donor criteria. Results: Both groups included mostly redo cases (A: 89.7% vs. B: 78.4%; p = 0.121). Incidences of donors with previous cardiac arrest (%) (A: 32.4 vs. B: 22.2; p < 0.05) or LV-hypertrophy (%) (A: 19.1 vs. B: 8.3; p = 0.119) were also increased in Group A. Ex situ time (min) was significantly longer in Group A (A: 381 (74) vs. B: 228 (43); p < 0.05). Ventilation time (days) (A: 10.0 (19.9) vs. B: 24.3 (43.2); p = 0.057), postoperative need for ECLS (%) (A: 25.0 vs. B: 39.2; p = 0.112) and postoperative dialysis (chronic) (%) (A: 4.4 vs. B: 27.5; p < 0.001) were numerically better in the OCS group, without any difference in the occurrence of early graft rejection. The 30-d-survival (A: 92.4% vs. B: 90.2%; p = 0.745) and mid-term survival were statistically not different between both groups. Conclusions: OCS heart allowed safe transplantation of surgically complex recipients with excellent one-year outcomes, despite long preservation times and unfavourable donor characteristics. Furthermore, we observed trends towards decreased ventilation times and fewer ECLS treatments. In times of reduced organ availability and increasing recipient complexity, OCS heart is a valuable instrument that enables otherwise infeasible allocations and contributes to increase surgical safety. Full article

Neutrophils have been suggested mediators of organ dysfunction in COVID-19. The current study investigated if systemic neutrophil activity, estimated by human neutrophil lipocalin (HNL) concentration in peripheral blood, is associated with acute kidney injury (AKI) development. A total of 103 adult patients admitted to intensive care, with PCR-confirmed SARS-CoV-2 infection, were prospectively included (Clinical Trials ID: NCT04316884). HNL was analyzed in plasma (P-HNL Dimer) and in whole blood (B-HNL). The latter after ex vivo activation with N-formyl-methionine-leucine-phenylalanine. All patients developed respiratory dysfunction and 62 (60%) were treated with invasive ventilation. Sixty-seven patients (65%) developed AKI, 18 (17%) progressed to AKI stage 3, and 14 (14%) were treated with continuous renal replacement therapy (CRRT). P-HNL Dimer was higher in patients with invasive ventilation, vasopressors, AKI, AKI stage 3, dialysis, and 30-day mortality (p < 0.001–0.046). B-HNL performed similarly with the exception of mild AKI and mortality (p < 0.001–0.004). The cohort was dichotomized by ROC estimated cutoff concentrations of 13.2 µg/L and 190 µg/L for P-HNL Dimer and B-HNL respectively. Increased cumulative risks for AKI, AKI stage 3, and death were observed if above the P-HNL cutoff and for AKI stage 3 if above the B-HNL cutoff. The relative risk of developing AKI stage 3 was nine and 39 times greater if above the cutoffs in plasma and whole blood, respectively, for CRRT eight times greater for both. In conclusion, systemically elevated neutrophil lipocalin, interpreted as increased neutrophil activity, was shown to be associated with an increased risk of severe AKI, renal replacement therapy, and mortality in COVID-19 patients with respiratory failure. Full article

qRT-PCR still remains the most widely used method for quantifying gene expression levels, although newer technologies such as next generation sequencing are becoming increasingly popular. A critical, yet often underappreciated, problem when analysing qRT-PCR data is the selection of suitable reference genes. This problem is compounded in situations where up to 25% of all genes may change (e.g., due to leukocyte invasion), as is typically the case in ARDS. Here, we examined 11 widely used reference genes for their suitability in commonly used models of acute lung injury (ALI): ventilator-induced lung injury (VILI), in vivo and ex vivo, lipopolysaccharide plus mechanical ventilation (MV), and hydrochloric acid plus MV. The stability of reference gene expression was determined using the NormFinder, BestKeeper, and geNorm algorithms. We then proceeded with the geNorm results because this is the only algorithm that provides the number of reference genes required to achieve normalisation. We chose interleukin-6 (Il-6) and C-X-C motif ligand 1 (Cxcl-1) as the genes of interest to analyse and demonstrate the impact of inappropriate normalisation. Reference gene stability differed between the ALI models and even within the subgroup of VILI models, no common reference gene index (RGI) could be determined. NormFinder, BestKeeper, and geNorm produced slightly different, but comparable results. Inappropriate normalisation of Il-6 and Cxcl1 gene expression resulted in significant misinterpretation in all four ALI settings. In conclusion, choosing an inappropriate normalisation strategy can introduce different kinds of bias such as gain or loss as well as under- or overestimation of effects, affecting the interpretation of gene expression data. Full article

Proper ventilation of a patient with an endotracheal tube (ETT) requires proper placement of the ETT. We present a sensitive, noninvasive, operator-free, and cost-effective optical sensor, called Opt-ETT, for the real-time assessment of ETT placement and alerting of the clinical care team should the ETT become displaced. The Opt-ETT uses a side-firing optical fiber, a near-infrared light-emitting diode, two photodetectors with an integrated amplifier, an Arduino board, and a computer loaded with a custom LabVIEW program to monitor the position of the endotracheal tube inside the windpipe. The Opt-ETT generates a visual and audible warning if the tube moves over a distance set by the operator. Displacement prediction is made using a second-order polynomial fit to the voltages measured from each detector. The system is tested on ex vivo porcine tissues, and the accuracy is determined to be better than 1.0 mm. In vivo experiments with a pig are conducted to test the performance and usability of the system. Full article