Biomedical subjects

Arne P Neyrinck

Publications and source records attributed to Arne P Neyrinck.

5 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

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↗