OBJECTIVES: To enable an increase in the numbers of donor lungs using organs from non-heart-beating donors (NHBD). To develop an isolated ventilation and perfusion technique to assess the degree of warm ischaemic organ injury suffered prior to retrieval, thereby enabling identification of lungs with predictably good post-transplant function. METHODS: Lungs from Landrace-Yorkshire White cross pigs were retrieved after 1 (NHBD(1)), 2 (NHBD(2)) or 4 h (NHBD(4)) post-hypoxic death induced by cessation of ventilation. Control organs were retrieved using standard techniques for each group from matched animals immediately following aortic cross-clamping (Control(1) and combined Control(2,4)). Modified Euro-Collins pulmoplegia was used in all groups, prior to ventilating a single lung with 100% oxygen and perfusion with neutrophil-depleted and deoxygenated blood. For all of the lungs in the NHBD(2) and combined Control(2,4) groups, and one of the successfully perfused NHBD(4), the contralateral lung was then transplanted with post-transplant function assessed for 12 h. All animals were anaesthetized throughout and euthanased without regaining consciousness. RESULTS: On assessment, oxygenation after 5 min of perfusion did not differ between NHBD(1) (n=4) vs. Control(1) (n=5; analysis of variance (ANOVA), P=0.152). However, oxygenation had deteriorated significantly in the NHBD(2) group (n=6) vs. Control(2,4) (n=8; ANOVA, P<0.0005) and was significantly poorer than initial values after 8 min (unpaired t-test with Bonferroni correction, P<0.03). In NHBD(4) (n=6), four lungs failed assessment due to the development of gross pulmonary oedema, although the remaining pair functioned as well as Control(2,4). Post-transplantation, NHBD(2) (n=6) contralateral lungs showed significantly poorer overall oxygenation, (mean+/-SD, 46+/-22 kPa) when compared with Control(2,4) (n=6; 59+/-16 kPa; ANOVA, P=0.001), although oxygenation was satisfactory. The contralateral organ from one successfully perfused NHBD(4) lung functioned well post-transplantation. CONCLUSIONS: The significant deterioration in oxygenating performance seen during assessment after 2 h warm ischaemia and the idiosyncratic function after 4 h warm ischaemia indicates the importance of functional testing of NHBD lungs. The similar deterioration in oxygenating performance seen post-transplantation in the contralateral lungs suggests that this method detects functional warm ischaemic lung injury.
OBJECTIVES: To enable an increase in the numbers of donor lungs using organs from non-heart-beating donors (NHBD). To develop an isolated ventilation and perfusion technique to assess the degree of warm ischaemic organ injury suffered prior to retrieval, thereby enabling identification of lungs with predictably good post-transplant function. METHODS: Lungs from Landrace-Yorkshire White cross pigs were retrieved after 1 (NHBD(1)), 2 (NHBD(2)) or 4 h (NHBD(4)) post-hypoxic death induced by cessation of ventilation. Control organs were retrieved using standard techniques for each group from matched animals immediately following aortic cross-clamping (Control(1) and combined Control(2,4)). Modified Euro-Collins pulmoplegia was used in all groups, prior to ventilating a single lung with 100% oxygen and perfusion with neutrophil-depleted and deoxygenated blood. For all of the lungs in the NHBD(2) and combined Control(2,4) groups, and one of the successfully perfused NHBD(4), the contralateral lung was then transplanted with post-transplant function assessed for 12 h. All animals were anaesthetized throughout and euthanased without regaining consciousness. RESULTS: On assessment, oxygenation after 5 min of perfusion did not differ between NHBD(1) (n=4) vs. Control(1) (n=5; analysis of variance (ANOVA), P=0.152). However, oxygenation had deteriorated significantly in the NHBD(2) group (n=6) vs. Control(2,4) (n=8; ANOVA, P<0.0005) and was significantly poorer than initial values after 8 min (unpaired t-test with Bonferroni correction, P<0.03). In NHBD(4) (n=6), four lungs failed assessment due to the development of gross pulmonary oedema, although the remaining pair functioned as well as Control(2,4). Post-transplantation, NHBD(2) (n=6) contralateral lungs showed significantly poorer overall oxygenation, (mean+/-SD, 46+/-22 kPa) when compared with Control(2,4) (n=6; 59+/-16 kPa; ANOVA, P=0.001), although oxygenation was satisfactory. The contralateral organ from one successfully perfused NHBD(4) lung functioned well post-transplantation. CONCLUSIONS: The significant deterioration in oxygenating performance seen during assessment after 2 h warm ischaemia and the idiosyncratic function after 4 h warm ischaemia indicates the importance of functional testing of NHBD lungs. The similar deterioration in oxygenating performance seen post-transplantation in the contralateral lungs suggests that this method detects functional warm ischaemic lung injury.
Authors: Edgardo E Guibert; Alexander Y Petrenko; Cecilia L Balaban; Alexander Y Somov; Joaquín V Rodriguez; Barry J Fuller Journal: Transfus Med Hemother Date: 2011-03-21 Impact factor: 3.747