Lung Transplantation With Grafts From Elderly Donors: A Single-Center Experience

Introduction

Use of extended criteria donors is one of the strategies to face the scarcity of donors for lung transplantation.

Methods

Between November 2002 and May 2009, we performed 52 LTs in 50 recipients, 10 of whom (group A) received lungs from donors aged 55 years or older (median, 58.5; range, 56-66 years) for comparison with 28 patients (group B) transplanted with lungs from donors younger than 55 years (median, 25.5; range, 15-54 years). We excluded 9 children and 3 recipients of combined liver plus lung transplantations from the study.

Results

Recipient age, gender, and indications for transplantation did not differ significantly between the 2 groups. Neither were there significant differences in PaO2/FiO2 ratios before lung retrieval, or length of the ischemic time The first PaO2/FiO2 on arrival to the intensive care unit (ICU) and the median length of ICU stay were similar. All patients, except 2 who died in the operating theatre, were extubated between 3 and 216 hours after the transplantation. Hospital mortality was similar in both groups: 3 patients in group A and 2 in group B (P = .1). The median portions of the predicted 1-second forced expiratory volume (FEV1) at 6 months after transplantation did not differ in the 2 groups: 62.4% in group A versus 70% in group B (P = .85).

Conclusion

Lung grafts from donors older than 55 years can be effectively used for transplantation, thus increasing the total organ pool.     

Liver Transplant From Controlled Cardiac Death Donors Using Normothermic Regional Perfusion: Comparison With Liver Transplants From Brain Dead Donors

Background

Liver transplantation from donors after either controlled or uncontrolled cardiac death (DCD) is associated with considerable rates of primary nonfunction (PNF) and ischemic cholangiopathy (IC). Normothermic regional perfusion (NRP) could significantly reduce such rates.

Hemoderivative Transfusion in Liver Transplantation: Comparison Between Recipients of Grafts From Brain Death Donors and Recipients of Uncontrolled Donors After Circulatory Death

IntroductionIntraoperative bleeding during liver transplantation has been correlated with a higher risk of morbidity and mortality and decrease in patient and graft survival.Materials and MethodsBetween January 2006 and December 2016 we performed 783 orthotopic liver transplants. After applying exclusion criteria, we found liver grafts from donors after circulatory death (DCD, group A) were used in 69 patients and liver grafts from donors after brain death (group B) were used in 265 patients.ResultsNo difference was found in terms of sex, body mass index, Model for End-Stage Liver Disease score, indication for transplantation, intensive care unit stay, and Child-Pugh score. The mean transfusion of hemoderivates was as follows: red blood cell 9 (0-28) units in group A vs 6 (0-20) units in group B (P = .004) and fresh frozen plasma 10 (0-29) units in group A vs 9.5 (0-23) in group B (P = .000). The only 2 factors related to massive blood transfusion (>6 units of red blood cell) were uncontrolled DCD condition (odds ratio = 2.38; 95% confidence interval, 1.32-4.31; P = .004), and higher Model for End-Stage Liver Disease score (odds ratio = 2.63; 95% confidence interval, 1.53-4.55; P = .001). Survival at 1, 3, and 5 years was 81.3%, 70.2%, and 68.9% in group A vs 89%, 83.7%, and 78% in group B (P = .070).ConclusionThe use of liver grafts from DCDs is associated with increased necessity of transfusion of hemoderivates in comparison with the use of liver grafts from donors after brain death.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.

Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.

Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).

Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.     

Liver Transplantation in Sexagenarian Patients Using Grafts From Uncontrolled Circulatory Death Versus Grafts From Brain Death Donation

BackgroundAn increased number of older recipients underwent liver transplantation in recent years, and consequently needing to obtain more liver grafts. In order to increase this pool, in 2006, we initiated the use of livers from uncontrolled circulatory death (uDCD). We analyzed the use of uDCD livers in sexagenarian recipients and their effect on overall survival.MethodsA retrospective and comparative study was performed among 4 groups according to recipient age (less or greater than 60 years) and donor type (donor brain death [DBD] or uDCD): Group A: DBD livers in recipients aged <60 years (n = 169); Group B: uDCD livers in recipients aged <60 years (n = 36); Group C: DBD livers in recipients aged >60 years (n = 96); and Group D: uDCD livers in recipients aged >60 years(n = 39).ResultsIntraoperative transfusion, biliary complications, primary non-function, acute rejection, chronic renal dysfunction, retransplantation, and mortality during follow-up (cardiovascular diseases in 3 patients, hepatitis C virus recurrence in 4 patients, and de novo malignancies in 3 patients) were significantly higher, and 5-year patient and graft survival was significantly lower in sexagenarian recipients.Bilirubin and packed red blood cells transfusion were risk factors for patient survival, whereas hepatocelular carcinoma, creatinine, and packed red blood cells transfusion were risk factors for patient survival. Recipient age (<60 years) was confirmed as protective factor for patient and graft survival, whereas the use of uDCD was not a risk factor for patient or graft survival.ConclusionsUse of a uDCD liver did not demonstrate as a risk factor for patient and graft survival, and recipient age (<60 years) was a protective factor for patient and graft survival.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non–heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non–heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non–heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.(Ann Thorac Surg 1997;63:1664–8)     

Impact of Ex Vivo Administration of Mesenchymal Stem Cells on the Function of Kidney Grafts From Cardiac Death Donors in Rat

Background

Mesenchymal stem cells (MSCs) have been applied to the treatment of various diseases, and MSC administration in marginal donor grafts may help avoid the ischemia–reperfusion injury associated with solid organ transplants. Given the reports of side effects after intravenous MSC administration, local MSC administration to the target organ might be a better approach. We administered adipose tissue–derived MSCs (AT-MSCs) ex vivo to donor rat kidneys obtained after cardiac death (CD).

Methods

Using male Lewis rats (8–10 weeks), and a marginal transplant model of 1hr CD plus 1hr sub-normothermic ET-Kyoto solution preservation were conducted. AT-MSCs obtained from double-reporter (luciferase–LacZ) transgenic Lewis rats were injected either systemically (1.0 × 10⁶ cells/0.5 mL) to bilaterally nephrectomized recipient rats that had received a marginal kidney graft (n = 6), or locally via the renal artery (500 μL ET-Kyoto solution containing the same number of AT-MSCs) to marginal kidney grafts, which were then preserved (1 hour; 22°C) before being transplanted into bilaterally nephrectomized recipient rats (n = 8). Serum was collected to assess the therapeutic effects of AT-MSC administration, and the recipients of rats surviving to Day 14 were separately evaluated histopathologically. Follow-up was by in vivo imaging and histological LacZ staining, and tumor formation was evaluated in MSC-injected rats at 3 months.

Results

Systemic injection of MSC did not improve recipient survival. In vivo imaging showed MSCs trapped in the lung that later became undetectable. Ex vivo injection of MSCs did show a benefit without adverse effects. At Day 14 after RTx, 75% of the rats in the AT-MSC–injected group (MSC[+]) had survived, whereas 50% of the rats in the AT-MSC–non-injected group (MSC[−]) had died. Renal function in the MSC(+) group was improved compared with that in the MSC(−) group at Day 4. LacZ staining revealed AT-MSCs attached to the renal tubules at 24 hours after RTx that later became undetectable. Histopathologic examination showed little difference in fibrosis between the groups at Day 14. No teratomas or other abnormalities were seen at 3 months.     

Experience of the Transplant Unit From Virgen de Las Nieves Hospital in Using Liver Grafts From Asystolic Donors

Given the shortage of donors, it has become increasingly necessary to use alternative sources to meet the growing demand for organs, and evolution in the use of asystolic donors is proving to be an important resource in helping to meet those needs. The goal of this study is to describe the initial results of our experience with Type II asystolic donation. An observational retrospective study was conducted to analyze the variables of four cases in this type of donation. After the analysis we conclude that, despite the limited number of cases in our series, the results are compatible with larger series and permit us to continue to value this method as a resource for broadening the donor pool.     

Orthotopic Liver Transplantation: Preliminary Analysis of Complications With Grafts From Elderly Donors

Objective

This study aims to determine if donor grafts of patients older than 65 years develop more post-transplantation complications than those of younger patients.

Technical Modifications of the Orthotopic Lung Transplantation Model in Rats With Brain-Dead Donors

BackgroundMicrosurgical lung transplantation in rats has allowed us to obtain new knowledge about lung transplantation. However, some aspects in human transplantation technique still have not been included in this model, which could interfere with the clinical interpretation and extrapolation of results.MethodsTwenty left lung transplantations were performed with a cuff technique and technical modifications, such as brain death induction, the control of ischemia time and retrograde perfusion in the donor and the controlled sequential reperfusion of the implanted lung in the recipient.ResultsSurvival rate was 80%. The transplanted lungs showed proper perfusion and ventilation with good permeability of the anastomoses. Signs of ischemia-reperfusion injury were observed in all animals while mild acute rejection was seen in half of them.ConclusionsThe shown model proves valid and is very similar to the procedure carried out in humans, which would reduce the number of possible variables derived from the surgical technique when extrapolating the study results to clinical use.     

尿激酶型纤溶酶原激活因子对雄性大鼠生育力影响的实验研究

目的:探讨尿激酶型纤溶酶原激活因子(uPA)对于奥硝唑所致的雄性不育大鼠生育力的影响。方法:10~12周龄成年雄性SD大鼠50只,随机分成5组,每组10只:奥硝唑模型组、uPA高剂量组、中剂量组、低剂量组和空白对照组。奥硝唑模型组和uPA各剂量组给予奥硝唑400 mg/(kg.d)灌胃,同时uPA高剂量组、中剂量组、低剂量组分别腹腔注射uPA 3 000 IU/(kg.d)、1 000 IU/(kg.d)、334 IU/(kg.d)。空白对照组给予等体积0.5%羧甲基纤维素钠灌胃,同时腹腔注射等量生理盐水。各组动物连续处理20 d后,观察动物的精液常规、睾丸和附睾功能以及与雌鼠交配情况。结果:①与空白对照组相比,奥硝唑模型组精子活动力和平均胚胎数显著降低(P<0.01)。②与模型组相比,uPA高剂量组精子活动力和平均胚胎数显著增加(P<0.01),而uPA中、低剂量组虽有所改善但无统计学意义。③uPA高剂量组精子日产量与模型组及空白对照组相比差异有显著性(P<0.05)。结论:uPA对奥硝唑引起的雄性大鼠不育起到改善作用。     

L-肉碱对奥硝唑所致弱精子症大鼠的治疗作用

目的:探讨L-肉碱(LC)对奥硝唑(ORN)所致的弱精子症雄性大鼠的治疗作用。方法:性成熟雄性SD大鼠(200～230g)40只,随机均分为5组,连续灌胃20d,1次/d,每次1ml。A组(对照组):0.5%的羧甲基纤维素钠(溶剂);B组:ORN[400mg/(kg.d)];C组:ORN[400mg/(kg.d)]+LC[100mg/(kg.d)];D组:ORN[800mg/(kg.d)];E组:ORN[800mg/(kg.d)]+LC[100mg/(kg.d)]。将各组半数大鼠末次给药24h后,麻醉处死,取附睾,进行精子活力检测,并对附睾尾精子进行计数,剩余大鼠进行交配实验。结果:①与A组相比,B组,D组附睾头和附睾尾精子活力显著降低(P<0.05);精子数目显著减少(P<0.05)。②与B组相比,C组精子活力明显升高(P<0.05),精子数目明显增多(P<0.05),与A组比较无显著差异(P>0.05)。③E组大鼠的精子活力没有显著的提高,精子数目无明显增多,并且与D组相比没有差别(P>0.05)。结论:LC治疗后能提高ORN所致弱精子症大鼠的精子活力,增加精子密度。     

外源性肺泡表面活性物质对大鼠呼吸机相关性肺损伤的保护作用

目的探讨气管注入肺泡表面活性物质(PS)对大鼠呼吸机相关性肺损伤(VILI)的保护作用及机制。方法将40只Wistar大鼠采用区组法随机分为对照组、高潮气量组(HV组)、VILI组和PS组4组,每组各10只。对照组未行机械通气,其余3组容量控制通气,PS组同时经气管内插管注入猪PS100mg/kg。监测心率、平均动脉压(MAP)、血气分析、肺湿/干重比(W/D)和支气管肺泡灌洗液(BALF)中白细胞计数,测定肺组织核因子-κB(NF-κB)活性和BALF中及血清白细胞介素-8(IL-8)浓度,并观察大体及光学显微镜下肺组织损伤的改变。结果损伤性机械通气后大鼠MAP及氧合指数(PaO2/FiO2)显著降低,而肺组织NF-κB活性和W/D显著增高。PS组与VILI组相比,MAP、PaO2/FiO2、肺组织NF-κB活性、BALF中白细胞计数、BALF及血清中IL-8浓度均有统计学意义(P<0.05)。组织学检查显示PS组较VILI组病变明显减轻。结论经气管注入PS可抑制VILI大鼠NF-κB基因表达,对VILI有保护作用。     

Similar Outcomes of Kidney Transplantations Using Organs From Donors After Cardiac Death and Donors After Brain Death

Background

To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased.

Formulation-dependent Brain and Lung Distribution Kinetics of Propofol in Rats

Background: Propofol when administered by brief infusion in a lipid-free formulation has a slower onset, prolonged offset and greater potency compared with an emulsion formulation. To understand these findings the authors examined propofol brain and lung distribution kinetics in rats.

Methods: Rats were infused with equieffective doses of propofol in emulsion (n = 21) or lipid-free formulation (n = 21). Animals were sacrificed at various times to harvest brain and lung. Arterial blood was sampled repeatedly from each animal until sacrifice. Deconvolution and moment analysis were used to calculate the half-life for propofol brain turnover (BT) and brain:plasma partition coefficient (Kp). Lung concentration-time profiles were compared for the two formulations.

Results: Peak propofol plasma concentrations for the lipid-free formulation were 50% of that observed for emulsion formulation, whereas peak lung concentrations for lipid-free formulation were 300-fold higher than emulsion formulation. Brain Kp calculated from tissue disposition curve and ratio of brain:plasma area under the curves were 8.8 and 13, and 7.2 and 9.1 for emulsion and lipid-free formulations, respectively. BT were 2.4 and 2.5 min for emulsion and lipid-free formulations, respectively.     

Experience of the Reina Sofia Hospital in Lung Transplantation From Donors Older Than Forty Years

Introduction

The shortage of suitable donors for lung transplantation (LT) has led to liberalization of criteria for donor selection. This study evaluated the outcomes of LT among a subset of patients receiving organs from standard donors older than 40 years of age.

Methods

We distributed patients who underwent LTs performed between 1993 and 2007 into 2 groups: Group A, donors younger than 40 years; and Group B, donors 40 years of age or older. We compared donor and recipient preoperative, operative, and recipient postoperative factors by univariate analyses.

Results

We reviewed 255 consecutive LT patients: Group A, 198 patients (78%); and Group B, 57 patients (22%). Donors from Group A showed longer intubation times (43 hours vs 34 hours; P = .026) and a better PaO2/FiO2 ratio (477 vs 454 mm Hg; P = .020), with no differences in other donor variables. Among patients dying of primary graft failure, 20% were from Group B versus 5.6% from Group A (P = .04). There were no differences in mortality or other postoperative variables. Survival rates did not differ between groups (70%, 62%, 52%, and 45% in Group A vs 60%, 45%, 45%, and 20% in Group B at 1, 3, 5, and 10 years, respectively; P = .13).

Conclusion

The use of ideal donors older than 40 years of age might be related to a higher incidence of primary graft failure. However, long-term survival is similar to that of recipients from younger donors.     

Two Hours of In Vivo Lung Perfusion Improves Lung Function in Sepsis-Induced Acute Respiratory Distress Syndrome

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Isoflurane Preconditioning Improves Long-term Neurologic Outcome after Hypoxic-Ischemic Brain Injury in Neonatal Rats

Background: Preconditioning the brain with relatively safe drugs seems to be a viable option to reduce ischemic brain injury. The authors and others have shown that the volatile anesthetic isoflurane can precondition the brain against ischemia. Here, the authors determine whether isoflurane preconditioning improves long-term neurologic outcome after brain ischemia.

Methods: Six-day-old rats were exposed to 1.5% isoflurane for 30 min at 24 h before the brain hypoxia-ischemia that was induced by left common carotid arterial ligation and then exposure to 8% oxygen for 2 h. The neuropathology, motor coordination, and learning and memory functions were assayed 1 month after the brain ischemia. Western analysis was performed to quantify the expression of the heat shock protein 70, Bcl-2, and survivin 24 h after isoflurane exposure.

Results: The mortality was 45% after brain hypoxia-ischemia. Isoflurane preconditioning did not affect this mortality. However, isoflurane preconditioning attenuated ischemia-induced loss of neurons and brain tissues, such as cerebral cortex and hippocampus in the survivors. Isoflurane also improved the motor coordination of rats at 1 month after ischemia. The learning and memory functions as measured by performance of Y-maze and social recognition tasks in the survivors were not affected by the brain hypoxia-ischemia or isoflurane preconditioning. The expression of Bcl-2, a well-known antiapoptotic protein, in the hippocampus is increased after isoflurane exposure. This increase was reduced by the inhibitors of inducible nitric oxide synthase. Inducible nitric oxide synthase inhibition also abolished isoflurane preconditioning-induced neuroprotection.     

Variable Ventilation Improves Perioperative Lung Function in Patients Undergoing Abdominal Aortic Aneurysmectomy

Background: Optimizing perioperative mechanical ventilation remains a significant clinical challenge. Experimental models indicate that "noisy" or variable ventilation (VV)-return of physiologic variability to respiratory rate and tidal volume-improves lung function compared with monotonous control mode ventilation (CV). VV was compared with CV in patients undergoing abdominal aortic aneurysmectomy, a patient group known to be at risk of deteriorating lung function perioperatively.

Methods: After baseline measurements under general anesthesia (CV with a tidal volume of 10 ml/kg and a respiratory rate of 10 breaths/min), patients were randomized to continue CV or switch to VV (computer control of the ventilator at the same minute ventilation but with 376 combinations of respiratory rate and tidal volume). Lung function was measured hourly for the next 6 h during surgery and recovery.

Results: Forty-one patients for aneurysmectomy were studied. The characteristics of the patients in the two groups were similar. Repeated-measures analysis of variance (group x time interaction) revealed greater arterial oxygen partial pressure (P = 0.011), lower arterial carbon dioxide partial pressure (P = 0.012), lower dead space ventilation (P = 0.011), increased compliance (P = 0.049), and lower mean peak inspiratory pressure (P = 0.013) with VV.