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1.
Luis H. Toledo-Pereyra Eduardo A. Santiago-Delpín 《Journal of investigative surgery》2013,26(6):331-332
We evaluated the production of the interleukins (ILs) IL1- &;#103 , IL-6, and IL-10 in both the vasculature and pulmonary tissue before and after 24 h of lung preservation. The cardiopulmonary blocs of 21 Balb-c mice were divided into three study groups (7 mice/group) and were flushed through the pulmonary artery with Krebs-Henseleit buffer (K-Hb) at 4°C at a rate of 0.2 mL/min as follows: Group 1, lung washout: lungs were flushed until pulmonary effluent was clear. Group 2, perfusion: After lungs were flushed until pulmonary effluent was clear, lungs were perfused during 30 min. Group 3, preservation: Lungs were flushed until pulmonary effluent was clear, and the cardiopulmonary bloc was preserved immersed into (K-Hb) at 4°C. After 24 h of preservation, lungs were reperfused during 30 min. In all study groups the caudal lobe from the left lung was taken for microscopical study; all other lobes were homogenized with (K-Hb) and the supernatant was obtained. IL-1 &;#103 , IL-6, and IL-10 production in lung effluents (washout, perfusion, and reperfusion) and in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA). In the lung effluent, there was no statistical difference between IL-1 &;#103 and IL-6 concentrations. In all study groups, IL-10 production was significantly higher than IL-1 &;#103 and IL-6 levels. IL-10 level was lowest in the 24-h preservation group when it was compared to the other groups. In group 1, there was a negative correlation ( r =-.599, p < .05) between IL-1 &;#103 and IL-10. In pulmonary tissue, IL-1 &;#103 was higher in group 2 when compared to groups 1 ( p = .001) and 3 ( p = .002), and it was significantly lower in group 3. IL-10 was lower in group 1 when compared to groups 2 ( p = .001) and 3 ( p = .004). In groups 1 and 2, IL-1 &;#103 was significantly higher than IL-6 and IL-10. In group 3, IL-10 was higher than IL-1 &;#103 ( p = .0001) and IL-6 ( p = .0001). Correlation of effluent/tissue index with histological findings showed a negative correlation between IL-10 effluent/tissue relation and inflammation ( r =-.68, p < .01). In conclusion, the main cytokine found in lung effluents was IL-10, followed by IL-6 and IL-1 &;#103 . On the other hand, cytokine concentration in lung tissue homogenates was mainly due to the presence of IL-1 &;#103 . However, this cytokine shows a significant reduction in lung tissue after prolonged preservation. 相似文献
2.
Effects of dibutyryl cyclic adenosine monophosphate on the ultrastructure of endothelial cells in rat lungs cold preserved for 15 hours 总被引:1,自引:0,他引:1
Ueda M Hasegawa S Nakamura T Hirata T Fukuse T Suzuki Y Wada H 《European surgical research. Europ?ische chirurgische Forschung. Recherches chirurgicales européennes》2000,32(5):289-296
BACKGROUND: Dibutyryl cyclic adenosine monophosphate (db-cAMP) has been shown to protect vascular endothelial cells by increasing the level of intracellular cAMP, and we have previously reported its effectiveness in lung preservation. Here, the effects of db-cAMP in lung preservation were ultrastructurally investigated, and the ultrastructural changes before reperfusion were correlated with pulmonary function after reperfusion. METHODS: The lungs of 17 Lewis rats were flushed with perfusate and prostaglandin E(1), and were then divided into three groups. In the fresh group (n = 6), the lungs were flushed with extracellular-type trehalose-containing (ET-K) solution and were reperfused immediately. In the control group (n = 6) and db-cAMP group (n = 5), the lungs were flushed with ET-K solution and ET-K solution plus db-cAMP (2 mM), respectively, and were reperfused after cold preservation at 4 degrees C for 15 h. Before reperfusion, tissue was sampled and ultrastructurally analyzed by transmission electron microscopy. RESULTS: In the endothelial cells of pulmonary arterioles, the incidence of protrusion was significantly lower in the fresh and db-cAMP groups than in the control group (p < 0.05). The incidence of detachment and microvillus formation were significantly lower in the fresh and db-cAMP groups than in the control group (p < 0.01). The ultrastructure of the alveoli did not allow separation of the control and db-cAMP groups. The shunt fraction and wet to dry weight ratio of the lung tissue after reperfusion were significantly lower in the fresh and db-cAMP groups than in the control group (p < 0.01). Positive correlations were found between the incidence of these ultrastructural changes in the endothelial cells of the pulmonary arterioles and pulmonary function after reperfusion. CONCLUSION: These findings suggest that db-cAMP might attenuate the lung injury caused by cold preservation and ischemia-reperfusion, partly by suppressing the acceleration of the structural changes in the endothelial cells in the pulmonary arterioles. 相似文献
3.
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. 总被引:1,自引:0,他引:1
Filip R Rega Bart M Vanaudenaerde Wim A Wuyts Nicole C Jannis Geert M Verleden Toni E Lerut Dirk E M Van Raemdonck 《The Journal of heart and lung transplantation》2005,24(1):20-28
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. 相似文献
4.
H Yokomise T Ueno F Yamazaki S Keshavjee A Slutsky G Patterson 《Transplantation》1990,49(6):1039-1043
Calcium channel blockers have recently been shown to improve pulmonary and myocardial preservation. The effect of verapamil on hypothermic lung preservation was investigated using an isolated ventilated rabbit lung perfusion model. In phase 1, preserved lungs were not flushed prior to extraction. Four groups of five animals were studied: group 1 (no verapamil), group 2 (verapamil administration prior to extraction), group 3 (verapamil at reperfusion only), group 4 (verapamil both prior to extraction and at reperfusion). In phase 2, two groups of five animals received pulmonary artery flush with low potassium (4 mmol/L), 2% low-potassium dextran (LPD) solution; group 1 (without verapamil), group 2 (flush and reperfusion with verapamil). As in phase 1, lungs were stored for 30 hr at 10 degrees C prior to reperfusion. In phase 3, the protocol was identical to phase 2, except that the storage time was extended to 48 hr. PO2 (mean +/- SE) of effluent blood in lungs treated with verapamil prior to extraction (122.8 +/- 5.0 mmHg) was significantly increased in comparison with lungs not receiving verapamil (69.0 +/- 3.3 mmHg) or only receiving verapamil at the time of reperfusion (87.1 +/- 11.9 mmHg). Gas exchange after 30 hr storage was equivalent in lungs flushed with LPD with or without verapamil. However verapamil did provide an advantage when preservation times were extended to 48 hr (62.3 +/- 8.5 mmHg, 46.9 +/- 2.3 mmHg). Verapamil administered prior to lung extraction provides better lung function following preservation, but has benefit over LPD flush only with extended periods of preservation (48 hr). 相似文献
5.
目的 观察联合应用异博定和还原型谷胱甘肽对兔肺脏保存的影响.方法 健康日本大耳白兔24对,随机分为4组,每组6对.D组用改良型低钾右旋糖酐液(对照组,改良LPD液)行肺灌洗保存,Y组用改良LPD液+异博定(2 mg/kg体重),H组用改良LPD液+还原型谷胱甘肽(3 mmol/L),L组用改良LPD液+异博定(2 mg/kg体重)+还原型谷胱甘肽(3 mmol/L).实验结束时取肺组织测定湿/干比,细胞内钙离子浓度,丙二醛(blDA)含量与超氧化物歧化酶(SOD)活性,并行细胞凋亡测定.结果 L组的肺组织湿/干比、细胞内钙离子浓度、丙二醛(NDA)含量与超氧化物歧化酶(SOD)活性均优于D组(P值均<0.01),细胞凋亡L组平均灰度值和阳性单位明显好于D组(P<0.01、P<0.05).结论 联合应用异博定和还原型谷胱甘肽对于肺缺血再灌注损伤的作用均优于两药单独应用. 相似文献
6.
Long-term (72 hours) preservation of rat lungs 总被引:2,自引:0,他引:2
Aguiló R Serra E Togores B de la Peña A Santos C Agustí AG 《The Journal of thoracic and cardiovascular surgery》2003,125(4):907-912
OBJECTIVE: We sought to investigate whether the addition of ethanol to a preservation solution (as an antifreeze agent) might allow a reduction of the storage temperature to 0 degrees C without causing freezing damage and improve lung function after prolonged (72 hours) ischemia. METHODS: Lungs from Sprague-Dawley rats were ventilated and perfused ex vivo at 37 degrees C for 60 minutes in the following experimental groups: (1) the no ischemia and reperfusion (no I-R) group (n = 7), in which lungs were studied immediately after harvesting; (2) the LPD24 (n = 7) and (3) LPD72 (n = 8) groups, in which, after harvesting, lungs were flushed and immersed in low-potassium dextran solution and stored deflated at 10 degrees C for 24 and 72 hours, respectively, until reperfusion; and (4) the TEST72 group (n = 9), in which lungs were flushed and immersed in Krebs-Henseleit buffer with added ethanol (10 mL/L) after harvesting and stored deflated at 0 degrees C for 72 hours until reperfusion. RESULTS: Compared with the no I-R group, the other 3 groups had worse lung function, higher lung water content, and evidence of cell injury at reperfusion (P <.01). However, lung function at reperfusion (assessed on the basis of either effluent Po(2), peak airway pressure, or mean arterial pulmonary pressure) was better (P <.01) in the TEST72 group than in the LPD24 or LPD72 groups. Paradoxically, lung cell structure was better preserved in the LPD24 group than in the TEST72 group (or the LPD72 group). CONCLUSIONS: In this experimental model of rat lung ischemia-reperfusion injury, a low preservation temperature (0 degrees C) combined with the addition of ethanol to the preservation solution improves lung function at reperfusion after 72 hours of ischemia but fails to maintain lung cell structure. 相似文献
7.
E Mayer J D Puskas P F Cardoso S Shi A S Slutsky G A Patterson 《The Journal of thoracic and cardiovascular surgery》1992,103(6):1136-1142
Pulmonary preservation is improved by hypothermia, but the optimal preservation temperature is not known. The effects of two different preservation temperatures, 4 degrees and 10 degrees C, on lung function were studied in a canine left lung allograft survival model allowing selective perfusion of either lung. After donor treatment with high-dose prostaglandin E1, (25 micrograms/kg), lungs were flushed with modified Euro-Collins solution (50 ml/kg) and stored in Euro-Collins solution for 18 hours at 4 degrees C in group I (n = 8) and 10 degrees C in group II (n = 6). Pulmonary gas exchange and hemodynamics were compared on the day of transplantation (day 0) and 3 days later (day 3). Rapid, high-flow, low-pressure flush was achieved uniformly in both groups (flush time: group I, 35.1 +/- 2.4 second; group II, 35.3 +/- 3.0 seconds; p = 0.96; flush pressure: group I, 9.8 +/- 0.7 mm Hg; group II, 10.1 +/- 1.1 mm Hg; p = 0.8). Transplanted lungs provided similar excellent oxygenation in both groups on day 0 (arterial oxygen tension, group I, 451 +/- 82 mm Hg; group II, 497 +/- 37 mm Hg; p = 0.61; inspired oxygen fraction = 1.0) and day 3 (arterial oxygen tension, group I, 551 +/- 57 mm Hg; group II, 587 +/- 19 mm Hg; p = 0.55), with a statistically significant improvement from day 0 to day 3 in both groups (group I, p = 0.034; group II, p = 0.038). There was no difference in arterial carbon dioxide tension, base excess, cardiac output, blood pressure or pulmonary artery pressure between the two groups. We conclude that a large bolus of prostaglandin E1 into the pulmonary artery produces a high-flow, low-pressure flush with modified Euro-Collins solution; with this technique, equivalent, reliable 18-hour lung preservation can be achieved at 4 degrees and 10 degrees C flush and storage temperatures. 相似文献
8.
L-精氨酸在离体肺保存中的作用 总被引:5,自引:0,他引:5
目的:研究一氧化氮前体L-精氨酸(L-Arg)在离体兔肺保存中的保护作用。方法:将14只新西兰兔随机分为2组,对照组以改良的Euro-Collins(ECS)液灌注及保存供肺,实验组以L-精氨酸(3mmol/L)加入改良的ECS液中灌注及保存供肺。冷保存6h。以自体血再灌注1h后,做肺静脉血气分析(PvO2),并测定血及肺组织中一氧化 氮(NO),超氧化物歧化酶(SOD),脂质过氧化物(LPO)含量及肺组织的超微结构以评价肺保护的效果。结果:再灌注后,实验组比对照组血氧分压显著提高(P<0.05)。实验组血及肺组织中NO及SOD含量较对照组高(P<0.05),LPO含量较对照组低(P<0.05),透射电镜检查实验组损伤轻于对照组,结论:肺保存不超过6h时,在改良的ECS液中加入L-Arg用于离体肺的灌注和保存,能减轻肺损伤。 相似文献
9.
Comparison of the University of Wisconsin preservation solution and other crystalloid perfusates in a 30-hour rabbit lung preservation model. 总被引:2,自引:0,他引:2
S Miyoshi S Shimokawa H Schreinemakers H Date W Weder B Harper J D Cooper 《The Journal of thoracic and cardiovascular surgery》1992,103(1):27-32
The University of Wisconsin solution, which contains a high potassium concentration (120 mmol/L), was evaluated for rabbit lung preservation by comparing it with a modified University of Wisconsin solution with low potassium (4 mmol/L), a low-potassium dextran solution (4 mmol/L), and simple surface cooling. In the first three groups rabbit lungs were flushed in situ with the solution (n = 5 in each group); then the lung-heart block was harvested and stored at 10 degrees C for 30 hours. In the surface cooling group the lungs were harvested without flushing and then simply immersed in saline and stored. For assessment, the stored lung was ventilated with room air and perfused with fresh venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function included gas analysis of effluent blood, mean pulmonary artery perfusion pressure, and peak airway pressure. Among these parameters, oxygen tension was most sensitive. Oxygen tension at 10 minutes' perfusion in the modified University of Wisconsin (95 +/- 6 mm Hg) and low-potassium dextran (99 +/- 4 mm Hg) groups was significantly higher than that in the surface cooling (61 +/- 7 mm Hg) and University of Wisconsin (51 +/- 7 mm Hg) groups. There was no difference between the modified University of Wisconsin and low-potassium dextran groups or between the surface cooling and University of Wisconsin groups. We conclude that the low-potassium University of Wisconsin solution is superior to the high-potassium University of Wisconsin solution and that the lactobionate and raffinose included in the University of Wisconsin solution as impermeants do not improve lung preservation in this model. 相似文献
10.
Efficacy of initial controlled perfusion pressure for ischemia-reperfusion injury in a 24-hour preserved lung. 总被引:1,自引:0,他引:1
In lung transplantation, the safety period of the ischemic time of the graft is within 6 hours. Because of the problem of donor shortage, it is essential to extend the safety period of the preservation time of the donor lung. However, the longer the preservation time is, the more severe is the resulting ischemia-reperfusion injury. This study was designed to evaluate the efficacy of initial controlled perfusion pressure in the reduction of ischemia-reperfusion injury in a 24-hour preserved lung. Japanese white rabbit lungs were flushed with a low-potassium dextran solution (4C, 500 ml) after injection of prostaglandin E1 (20 microgram, bolus via PA) and submersed in the same solution for 24 hours at 4C. After preservation, the left lung was reperfused using an extracorporeal lung perfusion model which comprised of a closed circuit combined with a membrane deoxygenator. Assessment of lung function included gas analysis of influent and effluent blood and mean pulmonary artery perfusion pressure. Then the lung wet/dry weight ratio was calculated. In group I of the control group (n=6), the left lung was reperfused immediately following flushing (without preservation) at a flow rate of 50 ml/min for 60 minutes. In groups II and III, grafts were stored for 24 hours. In group II, grafts (n=6) were reperfused at a flow rate of 50 ml/min for 60 minutes. In group III (n =6), the flow rate was controlled by maintaining the perfusion pressure below 30 mmHg during the initial 5 minutes and was increased to 50 ml/min for the subsequent 60 minutes. In group II, the mean pulmonary artery pressure during perfusion increased rapidly, and oxygenation deteriorated. All grafts developed pulmonary edema within 12 minutes after reperfusion. Examination of the specimen revealed that the peripheral lung was not perfused. In group III, the mean pulmonary artery perfusion pressure was maintained below 30 mmHg, and oxygenation was preserved sufficiently throughout the experiment (delta PO2 > 100 mmHg) with no significant difference from control values. In conclusion, ischemia-reperfusion injury of the 24-hour preserved lung was attenuated prominently by controlling initial perfusion pressure for 5 minutes. 相似文献
11.
Rega FR Neyrinck AP Verleden GM Lerut TE Van Raemdonck DE 《The Annals of thoracic surgery》2004,77(2):438-44; discussion 444
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. 相似文献
12.
Raffinose improves 24-hour lung preservation in low potassium dextran glucose solution: a histologic and ultrastructural analysis 总被引:5,自引:0,他引:5
Fischer S Hopkinson D Liu M MacLean AA Edwards V Cutz E Keshavjee S 《The Annals of thoracic surgery》2001,71(4):1140-1145
BACKGROUND: We have previously shown that the addition of raffinose to low potassium dextran (LPD) preservation solution improves transplanted rat lung function after 24 hours of storage. The mechanisms by which raffinose acts are unclear. The aim of this study was to examine the histologic and ultrastructural correlates of this enhanced pulmonary function after preservation with raffinose. METHODS: In a randomized, blinded study, rat lungs were flushed with LPD, or LPD containing 30 mmol/L of raffinose, and stored for 24 hours at 4 degrees C. Control lungs were flushed with LPD but not stored (n = 5 each group). Changes in postpreservation edema were determined. In addition, lungs were flushed with a trypan blue solution to quantify cell death, and examined using both light and electron microscopy. RESULTS: The LPD lungs gained significantly more weight (25.5%+/-5.5%) compared with raffinose-LPD lungs (5.2%+/-5.3%; p < 0.0001). There were higher percentages of dead cells in the LPD lungs (29%+/-0.3% of total cells) compared with raffinose-LPD lungs (14%+/-1.4%; p < 0.001) and control lungs (0.2%+/-5%; p < 0.001). Control lungs maintained normal ultrastructure, whereas LPD lungs showed a decreased number of intact type II pneumocytes and significant cellular necrosis. Interstitial and alveolar edema with interstitial macrophage infiltration was also observed. Alveolar capillaries were collapsed. In contrast, raffinose-LPD lungs showed only mild alterations such as minimal interstitial edematous expansion, fewer damaged cells, and minimal capillary injury. CONCLUSIONS: Raffinose exerts a cytoprotective effect on pulmonary grafts during preservation, which explains the previously documented improved function. This simple modification of LPD with raffinose may provide clinical benefit in extended pulmonary preservation. 相似文献
13.
Twenty-four-hour canine lung preservation using UW solution 总被引:3,自引:0,他引:3
K Kawahara H Ikari H Hisano T Takahashi S Honshou H Ayabe M Tomita 《Transplantation》1991,51(3):584-587
The left lungs of 14 mongrel dogs were isolated, preserved, and then reperfused for 120 min. Three groups of lungs were investigated: group 1, nonpreserved lungs (control n = 5); group 2, lungs were flushed with UW solution and cold-stored (4-6 degrees C) in the same flush solution for 24 hr (n = 4); and group 3, lungs flushed and cold-stored with modified Euro-Collins' solution for 24 hr (n = 5). Airway pressure (AWP), static lung compliance (Cst), and pulmonary vascular resistance (PVR) 120 min after reperfusion were significantly higher in group 3 compared with the lungs in group 1 and group 2. AWP was 18.7 +/- 3.9 in group 1, 21.1 +/- 3.8 in group 2, and 33.8 +/- 9.2 ml/cmH2O (mean +/- SD) in group 3 (P less than 0.05). Cst was 14.0 +/- 3.5, 10.8 +/- 1.5, and 6.2 +/- 1.2 ml/cmH2O, respectively (P less than 0.01). Pulmonary vascular resistance was 125 +/- 16, 120 +/- 42, and 410 +/- 108 mmHg/L/min (P less than 0.05). We conclude that UW solution is useful for hypothermic canine lung preservation. 相似文献
14.
Ueda M Kosaka S Hirata T Fukuse T Suzuki Y Hitomi S Wada H 《European surgical research. Europ?ische chirurgische Forschung. Recherches chirurgicales européennes》1999,31(2):162-172
Mitochondria of the small vasculature endothelial cells were examined in preserved rat lungs before and after reperfusion, and the ultrastructural changes were correlated with pulmonary function after reperfusion. Rat lungs were flushed with perfusate and prostaglandin E1 and divided into five groups (n = 5 in each group): group A, normal control group; group B, University of Wisconsin solution; group C, Euro-Collins solution; group D, ET-Kyoto solution, and group E, new ET-Kyoto solution. After preservation at 4 degrees C for 17 h, the left lungs were reperfused at 37 degrees C for 60 min. Tissue was sampled and mitochondria of the small vasculature endothelial cells were ultrastructurally analyzed by transmission electron microscopy before and after reperfusion. The ultrastructure of the mitochondria was well maintained in groups A, B and E before and after reperfusion. In group C, the number of severely degenerated mitochondria in the sectional area of 100 microm2 before reperfusion was 18.0 +/- 3.9, which was significantly larger than in the other groups (p < 0.01), and the total number of mitochondria significantly decreased with reperfusion (from 24.8 +/- 3.5 to 8.2 +/- 2.4, p < 0.05). In group C, the shunt fraction, mean pulmonary arterial pressure and the wet-dry ratio of the lung tissue after reperfusion C were significantly higher than in the other groups (p < 0.05; 76.3 +/- 1.5%, 54.8 +/- 4.2 mm Hg, and 20.6 +/- 2.5, respectively). A positive correlation was found between the percentage of the mitochondrial degeneration before reperfusion and the physiological parameters after reperfusion. Mitochondrial damage associated with cold ischemia is probably involved in lung injury caused by cold preservation and reperfusion. 相似文献
15.
H Date O Lima A Matsumura H Tsuji D A d'Avignon J D Cooper 《The Journal of thoracic and cardiovascular surgery》1992,103(4):773-780
Techniques for organ preservation generally use hypothermia to retard metabolic requirements. However, excessive hypothermia may also produce injury. Using a canine left lung allotransplantation procedure, we compared two preservation temperatures (4 degrees and 10 degrees C) in terms of subsequent lung function measured by temporary occlusion of the right pulmonary artery after implantation of the preserved left donor lung. The lungs were flushed with low-potassium dextran electrolyte solution, inflated with 100% oxygen, and preserved for 18 hours. To investigate possible changes of energy stores at different temperatures, we performed phosphorus 31-nuclear magnetic resonance analyses of lung samples. Sequential determinations of adenosine triphosphate levels in lung tissue preserved at 4 degrees, 10 degrees, and 22 degrees C were studied. After transplantation, lungs preserved at 10 degrees C (n = 6) provided significantly better arterial oxygen tension than those preserved at 4 degrees C (n = 6), 451 +/- 46 mm Hg versus 243 +/- 86 mm Hg (p less than 0.05), and lower pulmonary vascular resistance, 581 +/- 68 dynes.sec.cm-5 versus 1006 +/- 157 dynes.sec.cm-5 (p less than 0.05). Adenosine triphosphate levels at 4 degrees and 10 degrees C were stable and did not differ from each other at the end of the 18-hour preservation period: 0.86 +/- 0.04 mumol/gm wet weight for control versus 0.86 +/- 0.07 mumol/gm wet weight for 4 degrees C and 0.93 +/- 0.06 mumol/gm wet weight for 10 degrees C after 18 hours of preservation. Preservation at 22 degrees C caused a 28% depression of adenosine triphosphate after 18 hours of preservation. These results lead us to conclude the following: (1) Optimal temperature for lung preservation is in the vicinity of 10 degrees C, and (2) lung dysfunction caused by excessive hypothermia is not due to a failure to maintain adenosine triphosphate levels. We suspect that adenosine triphosphate is generated by oxidative phosphorylation during lung preservation. 相似文献
16.
T Ueno H Yokomise T Oka J Puskas E Mayer A S Slutsky G A Patterson 《Transplantation》1991,52(4):626-630
We studied the effect of a vasodilator (prostaglandin E1) as well as flush (F) and storage (S) temperatures (4 degrees C or 10 degrees C) on lung preservation in an isolated rabbit lung perfusion model. Low-potassium dextran (LPD) or Euro-Collins (E-C) solution was used as flush solution. Six groups of six animals were studied: group 1 (LPD, 4 degrees C F-S), group 2 (LPD with PGE1, 4 degrees C F-S), group 3 (E-C with PGE1, 4 degrees C F-S), group 4 (LPD, 10 degrees C F-S), group 5 (LPD with PGE1, 10 degrees C F-S), group 6 (E-C with PGE1, 10 degrees C F-S). After 18-hr preservation, left lungs alone were ventilated, and reperfused with fresh venous blood. PaO2, PaCO2, pulmonary artery pressure (PAP), tracheal pressure (Pt) during reperfusion, and wet/dry weight (W/D) ratios were measured. PaO2 after LPD with or without PGE1 was significantly higher than after E-C with PGE1 at 4 degrees C (95.8 +/- 11.5 mmHg in group 1 or 102.7 +/- 8.6 in group 2 vs. 41.8 +/- 10.5 in group 3, P less than 0.01) and at 10 degrees C (119.3 +/- 2.3 in group 4 or 131.1 +/- 6.2 in group 5 vs. 54.6 +/- 5.2 in group 6, P less than 0.01). PaCO2, PAP, Pt, and W/D ratios in the LPD groups were lower than in the E-C groups. LPD/PGE1 and LPD alone produced similar pulmonary preservation. PaO2 of lungs flushed with LPD and preserved at 10 degrees C was higher than that of lungs stored at 4 degrees C. We conclude that LPD solution is superior to E-C solution in this ex vivo rabbit lung preservation model, even when PGE1 is used. A moderate dose of PGE1 did not improve the performance of LPD as a flush solution. Pulmonary preservation with LPD at 10 degrees C is superior to preservation at 4 degrees C. 相似文献
17.
目的评价右美托咪定对单肺通气(one lung ventilation,OLV)患者血浆IL-8、IL-10及肺组织水通道蛋白(aquaporin,AQP)1表达的影响。方法择期行肺癌根治术患者40例,男23例,女17例,年龄40~75岁,ASAⅠ或Ⅱ级,采用随机数字表法将患者均分为两组:对照组(C组)和右美托咪定组(D组)。麻醉诱导前10 min,D组静注右美托咪定1μg/kg,随后以0.5μg·kg-1·h-1的速率输注至手术结束前30min,C组采用同样的方法静注等容量的生理盐水。于OLV前即刻(T1)、OLV 30min(T2)、60min(T3)、120min(T4)、恢复双肺通气后30min(T5)、术后2h(T6)取桡动脉血,测定血浆IL-8和IL-10的浓度。于OLV前即刻、肺叶离体时取肺组织,测定AQP1的表达。结果 T3~T6时C组及T3~T5时D组IL-8浓度,T2~T5时两组IL-10浓度明显高于T1时(P0.05);D组T3~T6时IL-8浓度明显低于,T2~T5时IL-10浓度明显高于C组(P0.05)。C组肺叶离体时AQP1表达明显低于OLV前即刻和D组(P0.05)。结论给予负荷量1μg/kg的右美托咪定,随后以0.5μg·kg-1·h-1的速率持续输注,可以降低单肺通气患者全身炎症反应,上调肺组织AQP1表达。 相似文献
18.
Calcium channel blocker enhances lung preservation. 总被引:2,自引:0,他引:2
S Sasaki K Yasuda J D McCully J LoCicero 《The Journal of heart and lung transplantation》1999,18(2):127-132
BACKGROUND: The standard program for lung transplantation employs PGE1 pretreatment for donor lungs, but its efficacy remains controversial. Calcium channel blocker has been reported more effective for reducing potassium-induced vasoconstriction. We investigate the efficacy of calcium channel blocker in the initial lung flush using rat lung transplant model. METHODS: The excised rat lungs (n = 30) were flushed with either University of Wisconsin solution (UWS) with a prior injection of 50 microg/kg PGE1 into the pulmonary artery (UWS + PGE1; n = 7), UWS only (UWS; n = 7), or UWS containing 10(-6) M nifedipine (UWS + Nif; n = 8). After storage (4 degrees C) for 24 hours, all lungs were reperfused for 2 hours using an isolated, pulsatile blood perfused lung model. Control lungs (n = 8) were reperfused immediately after harvest. Blood gas analysis and shunt fraction, lung airway resistance, dynamic lung compliance, and pulmonary vascular resistance were assessed. RESULTS: The pO2 at 30 minutes after reperfusion in the control, UWS, UWS + PGE1, and UWS + Nif group were 88.0 +/- 3.2, 49.6 +/- 2.2, 52.0 +/- 2.4, 85.1 +/- 2.1 (mmHg), respectively. Until 30 minutes after reperfusion, the pO2 in UWS and UWS + PGE1 group were significantly lower than those in UWS + Nif group (p < .001). Shunt fraction, lung airway resistance, and dynamic lung compliance also demonstrated the superiority of UWS + Nif group. CONCLUSIONS: The early graft function after storage was significantly enhanced in lungs flushed with UWS containing nifedipine. Calcium channel blocker is more effective than PGE1 in reducing the potassium-induced vasoconstriction. Optimal composition of the flush may require both calcium channel blocker for pulmonary vasodilation and PGE1 for pulmonary protection by non-vasodilatory mechanisms. 相似文献
19.
The effect of ischemic time and temperature on lung preservation in a simple ex vivo rabbit model used for functional assessment 总被引:7,自引:0,他引:7
L S Wang K Yoshikawa S Miyoshi K Nakamoto C M Hsieh F Yamazaki P F Guerreiro Cardoso H J Schaefers J Brito S H Keshavjee 《The Journal of thoracic and cardiovascular surgery》1989,98(3):333-342
Despite 25 years of research in lung transplantation, little progress has been made in methods for improving lung preservation. To evaluate many factors that may affect lung function after preservation, we have developed a simple, reliable, and inexpensive animal model. This consists of an isolated rabbit lung preparation perfused with blood and ventilated with a closed-circuit system. Heart-lung blocks were harvested and the left lung was assessed after ligation of the right pulmonary artery and right main-stem bronchus. On completion of a storage period, the left lung was ventilated and perfused with fresh rabbit venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function included gas analysis of infused and effluent blood, oxygen uptake, mean pulmonary artery perfusion pressure, and mean airway pressure. A control group and six preservation groups were evaluated, each with different storage temperatures (38 degrees C, 34 degrees C, 23 degrees C, 15 degrees C, 10 degrees C, and 4 degrees C). For each temperature, ischemic periods ranging from 1 to 30 hours were studied. In the control group, the lungs were assessed immediately after being harvested. In the preservation groups, the lungs were kept partially inflated, stored at a predetermined temperature by immersion, and later assessed after variable ischemic periods. Our studies demonstrated the following: (1) The degree of impaired lung function produced by ischemia is reflected by a decrease in oxygen uptake and in oxygen tension of the effluent pulmonary venous blood and an increase in pulmonary artery perfusion pressure; (2) hypothermia improves ischemic tolerance; (3) preservation of lung at 10 degrees C is superior to preservation at 15 degrees C and 4 degrees C. This screening model has allowed evaluation of independent multiple factors and methods pertinent to lung preservation and enables one to assess lung function reliably and rapidly. 相似文献
20.
T Wittwer T Wahlers A Fehrenbach J F Cornelius S Elki M Ochs H Fehrenbach J Albes A Haverich J Richter 《The Journal of heart and lung transplantation》1999,18(7):684-692
BACKGROUND: The poor tolerance of the lung to ischemia and reperfusion (IR) still represents one of the limitations in clinically successful lung transplantation. Modified Euro-Collins (EC) is routinely used in lung preservation, but alternative solutions have been developed for improvement of pulmonary preservation. Celsior is an extracellular solution that has significantly reduced the IR-induced pulmonary damage in animal studies. So far, no extensive experimental studies exist concerning the influence of Celsior on pulmonary gas exchange following IR. METHODS: In an extracorporeal rat lung model 10 lungs, each, were preserved with Celsior (CE) and Celsior/prostacyclin (CEPC, 6 microg/100 ml) at 4 degrees and 15 degrees C, each, and compared to low-potassium Euro-Collins (EC-40, 40 mmol/liter potassium). After 2 hours of ischemia lungs were reventilated and reperfused using a roller pump. Oxygenation in terms of oxygen partial tension in the left atrial effluent, pulmonary vascular resistance (PVR), peak inspiratory pressure, and wet/dry ratio were monitored for 50 minutes. Furthermore, edema formation was evaluated by light microscopy. Statistical analysis was performed using ANOVA models. RESULTS: Compared to the EC-40 group, oxygenation was increased and amount of edema was reduced in most Celsior-preserved organs (p<0.032) with exception of the CEPC group at 4 degrees C (p = 0.06). Additional application of prostacyclin did not have any significant effect on oxygenation in the Celsior group. However, after temperature elevation of the CEPC perfusate to 15 degrees C, a superior partial tension of oxygen was observed (p<0.023) in contrast to the 4 degrees C groups CE and CEPC. The lowest PVR was found in the CE 4 degrees C group (p<0.02). CONCLUSIONS: Celsior provides better lung preservation than EC-40 solution. Application of prostacyclin at higher perfusate temperatures results in additional functional improvement. In vivo experiments and ultrastructural analysis are warranted for further evaluation of Celsior in lung preservation. 相似文献