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Biomedical subjects

Dirk E M Van Raemdonck

Publications and source records attributed to Dirk E M Van Raemdonck.

11 recordsLinked to original sources
PubMed2006

Comparative study of donor lung injury in heart-beating versus non-heart-beating donors.

OBJECTIVE: The use of non-heart-beating donors (NHBD) has been advocated as an alternative to overcome the critical organ shortage in lung transplantation despite the warm ischemic period that may result in primary graft dysfunction. On the contrary, brain death in the heart-beating donor (HBD) may be an underestimated risk factor for donor lung injury. We postulated that 60 min of warm ischemia in the NHBD is less detrimental to the lung than the pathophysiological changes after brain death in the HBD. In this study we compared the quality of lungs from HBD versus NHBD in an isolated reperfusion model. METHODS: Pigs (n=10 per group) were divided into three groups. In group I (HBD), brain death was induced by acute inflation of an intracranial epidural balloon catheter. In group II (CONTROL), the balloon was not inflated. In group III (NHBD), cardiac arrest was induced by myocardial fibrillation. After 5 h of in situ mechanical ventilation, lungs in HBD and CONTROL were preserved with a cold antegrade flush. In NHBD, unflushed grafts were explanted after 1 h of warm ischemia and 4 h of topical cooling in the cadaver. Graft performance was evaluated during 1 h in an isolated ventilation and reperfusion model. Extravascular lung water content (EVLW) was calculated. All data are reported as mean+/-SEM. RESULTS: A significant autonomic storm was observed in HBD following balloon inflation. During ex vivo assessment, pulmonary vascular resistance (PVR) at 60 min in HBD (2634+/-371 dynes cm(-5)) was significantly higher as compared with that of CONTROL and NHBD (1894+/-137 dynes s cm(-5) and 1268+/-111 dynes s cm(-5), respectively; p<0.05). Plateau airway pressure (Plateau AwP) was also higher in HBD (17+/-1cmH2O) compared with that of CONTROL (12+/-1 cmH2O; p<0.05) and NHBD (14+/-1 cmH2O; not significant). No significant differences were observed between HBD, CONTROL and NHBD in EVLW (79+/-1%, 79+/-0% and 78+/-1%, respectively), and in PO2/FiO2 (564+/-58 mmHg, 622+/-14 mmHg and 578+/-26 mmHg, respectively). CONCLUSIONS: These data indicate that 1-h warm ischemic lungs in our model are less susceptible to ischemia-reperfusion injury than lungs retrieved 5 h after brain death. This study further supports the use of lungs from NHBD for pulmonary transplantation.

Airway Resistance↗
PubMed2006

Impact of warm ischemia on different leukocytes in bronchoalveolar lavage from mouse lung: possible new targets to condition the pulmonary graft from the non-heart-beating donor.

BACKGROUND: The use of non-heart-beating donors (NHBDs) for lung transplantation is a possible alternative for increasing the number of organs available. The warm ischemic period after circulatory arrest may contribute to a higher degree of primary graft dysfunction, resulting from ischemia-reperfusion injury (IRI). A better understanding of the role of inflammatory cells during the warm ischemic interval may be useful for developing new therapeutic strategies against IRI. METHODS: Mice were divided in 7 groups (n = 6/group). In 3 groups, ischemia was induced by clamping the hilum of the left lung for 30, 60 or 90 minutes (Groups [30I], [60I] or [90I], respectively). In 3 more groups, the lung was reperfused for 4 hours after identical ischemic intervals (Groups [30I+R], [60I+R] or [90I+R], respectively). Surgical impact was evaluated in a sham group ([sham]). Total and differential cell counts and interleukin-1beta (IL-1beta) protein levels in bronchoalveolar lavage (BAL) were determined and their correlations were investigated. RESULTS: Total cell, macrophage and lymphocyte numbers and IL-1beta protein levels increased progressively with longer ischemic intervals. A significant rise in BAL macrophages and lymphocytes was observed between [60I] and [90I] (p < 0.01 and p < 0.001, respectively). BAL neutrophils only increased after reperfusion with longer ischemic intervals. A positive correlation was found in the ischemic groups between IL-1beta levels and the number of macrophages (r = 0.62; p = 0.0012) and the number of lymphocytes (r = 0.68; p = 0.0002). A positive correlation was found in the reperfusion groups between IL-1beta levels and the number of neutrophils (r = 0.48; p = 0.044). CONCLUSIONS: This study demonstrates for the first time that BAL macrophages and lymphocytes increase significantly during warm ischemia and correlate with IL-1beta levels.

Animals↗
PubMed2005

IL-1beta in bronchial lavage fluid is a non-invasive marker that predicts the viability of the pulmonary graft from the non-heart-beating donor.

BACKGROUND: Viability testing of the pulmonary graft retrieved from the non-heart-beating donor (NHBD) is mandatory for successful outcome after lung transplantation. Functional assessment by ex vivo reperfusion, however, remains a cumbersome procedure. In this study, therefore, we wanted to investigate the possible value of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) measured in bronchial lavage fluid (BLF) in predicting functional outcome of the pulmonary graft after reperfusion. METHODS: Domestic pigs (29.9 +/- 0.56 kg) were sacrificed and divided in 5 groups (n = 5/group). In the non-ischemic group (NHBD-0), the heart-lung block was explanted immediately. In the other groups the animals were left untouched with increasing time intervals (1 hour = NHBD-1; 2 hours = NHBD-2; 3 hours = NHBD-3). Thereafter both lungs were cooled topically via chest drains up to a total ischemic interval of 4 hours. Finally, in the heart-beating donor group lungs were flushed and stored for 4 hours (4 degrees C) [HBD]. BLF samples were taken from the right lung in all groups after explantation for measurement of IL-1beta and TNF-alpha and the left lung was prepared for evaluation in an isolated reperfusion circuit. Haemodynamic, aerodynamic and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Graft function deteriorated with increasing time intervals after death. A strong correlation was found between the increase of IL-1beta concentration measured in BLF and the increase in pulmonary vascular resistance (r = 0.80), mean airway pressure (r = 0.74) and wet-to dry weight ratio (r = 0.78); (p < 0.0001, for all parameters). No significant differences in TNF-alpha levels in BLF were observed amongst groups (p = 0.933). CONCLUSIONS: IL-1beta in BLF prior to reperfusion correlated well with graft function and may therefore be a useful, non-invasive marker that can predict the viability of the pulmonary graft from the NHBD.

Animals↗
PubMed2005

Effect of azithromycin on bronchiectasis and pulmonary function in a heart-lung transplant patient with severe chronic allograft dysfunction: a case report.

Azithromycin has been shown to be beneficial in several diseases with chronic neutrophilic inflammation of the airways, such as cystic fibrosis and bronchiolitis obliterans syndrome (BOS) after lung transplantation. Up to now, however, its healing effect on bronchiectasis has never been demonstrated. We report a heart-lung transplant patient who developed chronic rejection (BOS stage 3) with the appearance of gross bronchiectasis on a spiral computed tomography (CT) chest scan. Within 2 weeks after starting azithromycin, the patient's forced expiratory volume in 1 second increased significantly and a repeat spiral CT chest scan 5 months later, showed a major improvement of the bronchiectasis. This case report illustrates that bronchiectasis may greatly improve after treatment with azithromycin and no longer needs to be considered an endstage finding in patients with severe BOS.

Adolescent↗
PubMed2005

Nebulized N-acetyl cysteine protects the pulmonary graft inside the non-heart-beating donor.

BACKGROUND: The use of lungs from non-heart-beating donors (NHBD) might significantly alleviate the organ shortage. The tolerable warm ischemic period after cardiac arrest, however, is limited to approximately 1 hour. If the lung could be safely protected inside the cadaver, this time period may be prolonged. This would help to obtain family consent and to organize organ retrieval. METHODS: Pigs (30.8 +/- 0.6 kg) were killed, left untouched for 3 hours, and divided into 3 groups. Nebulized N-acetyl cysteine (NAC) (300 mg), a precursor of the antioxidant agent glutathione, was administered during 10 minutes before death in Group I (NAC-NHBD, n = 6) and 15 minutes after death in Group II (NHBD-NAC, n = 6). In the control group, no aerosol was administered (NHBD, n = 6). After a warm ischemic interval of 3 hours, both lungs in all groups were topically cooled for 1 hour. Thereafter, the left lung was prepared for evaluation in an isolated reperfusion circuit. Hemodynamic, aerodynamic, and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. The right lung was used to measure reduced glutathione (GSH) and oxidized glutathione (GSSG) levels (micromol/g) in lung homogenates and total protein levels in bronchial lavage fluid. RESULTS: Pulmonary vascular resistance, mean airway pressure, and W/D were significantly decreased in NAC-NHBD (1930 +/- 144 Dynes x sec x cm(-5), 14.2 +/- 0.5 cm H2O, and 7.4 +/- 0.4; p < 0.01, 0.01, and 0.05, respectively) and NHBD-NAC (1837 +/- 180 Dynes x sec x cm(-5), 13.3 +/- 1.2 cm H2O, and 7.3 +/- 0.3; p < 0.01, 0.05, and 0.05, respectively) when compared with the control group (5051 +/- 530 Dynes x sec x cm(-5), 17 +/- 0.4 cm H2O, 8.5 +/- 0.1, respectively). GSH/GSSG ratio was significantly higher and protein levels were significantly lower in NAC-NHBD (1.7 +/- 0.1 and 1315 +/- 60 microg/ml; p < 0.05 and 0.05, respectively) and NHBD-NAC (1.7 +/- 0.2 and 1475 +/- 159 microg/ml; p < 0.05 and 0.05, respectively) when compared with the control group (1.2 +/- 0.1 and 2150 +/- 200 microg/ml). CONCLUSIONS: Nebulized NAC administered before or shortly after death attenuates early ischemia reperfusion injury via upregulation of glutathione. NAC might be a promising tool to protect the pulmonary graft from both controlled and uncontrolled NHBD.

Acetylcysteine↗
PubMed2004

How long can we preserve the pulmonary graft inside the nonheart-beating donor?

BACKGROUND: The use of lungs from nonheart-beating donors (NHBD) might significantly alleviate the organ shortage. Extending the preharvest interval in NHBD would facilitate distant organ retrieval. We hypothesized that prolonged topical cooling inside NHBD after 60 minutes of initial warm ischemia would not affect the pulmonary graft. METHODS: Domestic pigs were anesthetized and divided into three groups (n = 6 in each group). In the control group (HBD), lungs were flushed, explanted, and further stored in low potassium dextran solution (4 degrees C) for 4 hours. In the two study groups pigs were sacrificed by myocardial fibrillation and left untouched for 1 hour. Chest drains were then inserted for topical lung cooling (6 degrees C) for 3 hours (NHBD-TC3) or 6 hours (NHBD-TC6). The left lung in all groups was then prepared for evaluation. In an isolated circuit lungs were ventilated and reperfused through the pulmonary artery. Hemodynamic, aerodynamic, and oxygenation variables were measured 35 minutes after onset of controlled reperfusion. Wet-to-dry weight ratio was calculated. RESULTS: No significant differences were observed among the three groups in pulmonary vascular resistance (p = 0.38), mean airway pressure (p = 0.39), oxygenation index (p = 0.62), and wet-to-dry weight ratio (p = 0.09). CONCLUSIONS: These data confirm that 1 hour of warm ischemia does not affect the pulmonary graft from NHBD compared with HBD. The preharvest interval can be safely extended up to 7 hours postmortem by additional topical cooling of the graft inside the cadaver. This technique may facilitate distant organ retrieval in NHBD.

Animals↗
PubMed2004

Non-heart-beating donors.

The widespread application of lung transplantation is limited by the shortage of suitable donor organs resulting in longer waiting times for listed patients with a substantial risk of dying before transplantation. To overcome this critical organ shortage, some transplant programs have now begun to explore the use of lungs from circulation-arrested donors, so called non-heart-beating donors (NHBDs). This review outlines the different categories of NHBDs, the relevant published experimental data that support the use of lungs coming from these donors and the clinical experience worldwide so far. Techniques for NHBD lung preservation and pretransplant functional assessment are reviewed. Ethical issues involved in transplanting lungs from asystolic donors are discussed.

Humans↗
PubMed2003

Should we ventilate or cool the pulmonary graft inside the non-heart-beating donor?

BACKGROUND: The ideal preservation method during the warm ischemic period in the non-heart-beating donor (NHBD) remains unclear. In this study we compare the protective effect of ventilation vs cooling of the non-perfused pulmonary graft. METHODS: Domestic pigs (30.8 +/- 0.35 kg) were divided into 3 groups. In Group I, lungs were flushed with cold Perfadex solution, explanted and stored in saline (4 degrees C) for 4 hours (HBD, n = 5). Pigs in the 2 study groups were killed by myocardial fibrillation and left untouched for 1 hour. Lungs in Group II were ventilated (NHBD-V, n = 5) for 3 hours. Lungs in Group III were topically cooled (NHBD-TC, n = 5) in situ for 3 hours with saline (6 degrees C) infused via intra-pleural drains. Thereafter, the left lungs from all groups were prepared for evaluation. In an isolated circuit the left lungs were ventilated and reperfused via the pulmonary artery (PA) with autologous, hemodiluted, deoxygenated blood. Hemodynamic, aerodynamic and oxygenation parameters were measured at 37.5 degrees C and a PA pressure of 20 mm Hg. The wet:dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Pulmonary vascular resistance, oxygenation index and W/D weight ratio were significantly worse in NHBD-V (3,774 +/- 629 dyn sec cm(-5), 3.43 +/- 0.5, 6.98 +/- 0.42, respectively) compared with NHBD-TC (1,334 +/- 140 dyn sec cm(-5), 2.47 +/- 0.14, 5.72 +/- 0.24, respectively; p < 0.01, p < 0.05 and p < 0.05, respectively) and HBD (1,130 +/- 91 dyn sec cm(-5), 2.25 +/- 0.09, 5.23 +/- 0.49, respectively; p < 0.01, p < 0.01 and p < 0.05, respectively groups). No significant differences were observed, however, in any of these parameters between NHBD-TC and HBD (p = 0.46, p = 0.35 and p = 0.12, respectively). CONCLUSION: These results indicate that cooling of the pulmonary graft inside the cadaver is the preferred method in an NHBD protocol. It is also confirmed that 1 hour of warm ischemia does not diminish graft function upon reperfusion.

Animals↗
PubMed2003

Long-term preservation with interim evaluation of lungs from a non-heart-beating donor after a warm ischemic interval of 90 minutes.

OBJECTIVE: To investigate the value of in situ preservation and ex vivo evaluation of lungs from a non-heart-beating donor (NHBD) prior to long-term cold storage. SUMMARY BACKGROUND DATA: The use of pulmonary grafts from NHBD might alleviate the organ shortage. However, viability testing of these grafts is mandatory to transplant only those lungs with excellent function. METHODS: Pigs were divided into two groups. In the control group, lungs were flushed, explanted, and stored for 4 hours (4 degrees C). In the study group, pigs were killed and left untouched for 90 minutes. Thereafter, the lungs were cooled for 150 minutes via chest drains. Graft function of the left lung in both groups was assessed in an isolated ventilation and reperfusion circuit 4 hours after death. The lung was then cooled and stored. Twenty-four hours after death, the pulmonary graft was reassessed in the same model. RESULTS: We did not observe a statistical significant difference between the two groups in pulmonary vascular resistance, mean airway pressure, and partial oxygen tension at each time point. There was also no statistical significant difference in wet-to-dry weight ratio. Finally, no statistical difference was found within both groups comparing the assessment at 24 hours with the interim evaluation at 4 hours. CONCLUSIONS: These data demonstrate that: 1) 90 minutes of warm ischemia and 150 minutes of intrapleural cooling do not affect pulmonary graft function; and 2) NHBD lungs can be safely preserved up to 24 hours. Finally, we have demonstrated that interim ex vivo evaluation of NHBD lungs is a valid and safe method to assess graft function.

Animals↗
PubMed2003

The role of leukocyte depletion in ex vivo evaluation of pulmonary grafts from (non-)heart-beating donors.

If lungs could be retrieved for transplantation after circulatory arrest, the shortage of donors might be significantly alleviated. An important issue in using lungs from these so-called non-heart-beating donors is the development of a technique to assess their quality prior to transplantation without jeopardizing the life of the recipient. In our laboratory we tested the reliability of an ex vivo model for such an evaluation. We used pig lungs from optimal control animals, in casu heart-beating donors. This model enabled us to preserve and evaluate lungs with perfect function up to 24 hours after death. The intermediate assessment is performed in an isolated circuit where the lungs are being ventilated and reperfused via the pulmonary artery (PA) with autologous and haemodiluted blood. Haemodynamic, aerodynamic and oxygenation parameters are measured at 37.5 degrees C and a maximum PA pressure of 20 mmHg. These data were correlated with premortem values. During this ex vivo evaluation, leukocyte depletion plays an important role since neutrophils have been recognized as critical components in the inflammatory cascade, which is responsible for graft dysfunction soon and long after transplantation.

Animals↗