Leukocyte-depleted Blood Research Articles

A Convolutional Neural Network- Based Deep Learning To Detect Reticulocytes From Human Peripheral Blood

Machine learning approaches are rapidly augmenting, and in some cases, replacing the conventional methods in biomedical data analysis; to reduce time, cost, biases, and the need for sophisticated analytical platforms. Hence, significant interest has been compounded in the integration of automated image analysis for various clinical applications, such as the detection of infected or inflamed wounds, bone fractures or for the purpose of disease diagnosis – such as Plasmodium parasites or circulating tumour cells in blood. Here, we report the development of a Convolutional Neural Network (CNN)-based method on CPU to distinguish and count immature human red blood cells known as reticulocytes from blood smears. Reticulocytes represent a heterogeneous and relatively small percentage of cells in peripheral blood, and contain residual RNA in complex with proteins which generates thread-like patterns when stained with New Methylene Blue (NMB) dye. We used more than 200 NMB-stained images from leukocyte-depleted blood to train and optimize the model for immature reticulocytes (stained positive with NMB, intensity and pattern of which depends on the developmental stage of the reticulocyte) and mature RBCs (no staining with NMB). The training performance evaluation metrics demonstrated a mean average precision (mAP50) of 0.88, a precision of 0.83, a recall of 0.88, and an F1 score of 0.87. Our model was able to successfully count reticulocytes with accuracy more than 90% from unknown samples which were subsequently cross-verified through microscopy and counting. Given the importance of reticulocyte dynamics in blood and its clinical relevance, the newly developed model will find important easy to adopt biomedical applications that can be achieved on a simple PC.

Narrative review of aplastic anemia-the importance of supportive treatment.

Aplastic anemia (AA) is a rare, life-threatening syndrome of bone marrow failure resulted from bone marrow hypoplasia or aplasia, leading to pancytopenia (not only anemia). The most common cause is an autoimmune reaction of T lymphocytes against hematopoietic stem cells or, less frequently, a congenital defect or acquired damage to these cells, which leads to inhibition of their division and differentiation. AA can develop quickly (within a few days) or slowly (several weeks or months). The signs and symptoms are related to anemia, neutropenia, and thrombocytopenia. The concepts of treatment of patients with AA have significantly evolved in recent years. This is due to improved outcomes of both family and unrelated donor hematopoietic stem cell transplantations (HSCTs) as well as to revised results of immunosuppressive therapy (IST). The choice of the method depends essentially on three factors: the severity of AA, the age of the patient, matched sibling donor. All patients diagnosed with AA require appropriate supportive treatment adapted to the current clinical situation. Supportive treatment is necessary both before, during and after invasive causal treatment, it mainly involves the transfusion of leukocyte-depleted blood components, the use of anti-infectious prophylaxis or treatment of infections. In many cases AA, supportive therapy is the only therapeutic option, especially in elderly patients with comorbidities. In this paper we present current supportive treatment in this life-threatening disease.

The administration of argon during ex vivo normothermic perfusion in an experimental model of kidney ischemia–reperfusion injury

BackgroundArgon has shown potential as an organoprotective agent in numerous models of ischemia–reperfusion injury (IRI). The aim of this study was to evaluate the effects of argon gas during ex vivo normothermic perfusion (EVNP) in an experimental porcine model of kidney IRI. Materials and methodsAfter a warm ischemia time of 15 min and 17 h of static cold storage, porcine kidneys underwent 1 h of EVNP using leukocyte-depleted blood. During EVNP, kidneys were perfused with a gas composition either of 70% argon (n = 6), 70% nitrogen control (n = 6), or standard 95% oxygen (n = 6) balanced with 5% carbon dioxide. After EVNP, kidneys were reperfused with whole blood under standard conditions for 3 h to assess renal function and injury. ResultsDuring 1-h EVNP, the mean renal blood flow was numerically higher in the argon group (49.2 ± 16.2 mL/min/100 g; P = 0.320) compared with the nitrogen and oxygen groups (42.9 ± 18.64 and 37.71 ± 7.0 mL/min/100 g, respectively). Other measures of renal function and hemodynamics were not significantly different between the argon and control groups during this period.During reperfusion, no significant differences were found in functional parameters or inflammatory markers (P < 0.05). Histologic analysis revealed no significant change in morphology or hypoxia-inducible factor-1 alpha staining between gaseous groups. Nuclear hypoxia-inducible factor-1 alpha staining was observed only after 3 h of reperfusion. ConclusionsOur findings suggest that using 70% argon during 1 h of EVNP does not mediate a measurable organoprotective effect in an experimental porcine model of IRI.

Lowering Perfusate Temperature From 37°C to 32°C Diminishes Function in a Porcine Model of Ex Vivo Kidney Perfusion.

BackgroundEx vivo perfusion (EVP) is a novel method of preservation. However, optimal perfusion conditions remain undetermined. Reducing the temperature of the perfusate to subnormothermia may be beneficial during EVP and improve early graft function. The aim of this study was to investigate whether subnormothermia would influence the conditioning effect of EVP when compared with normothermic perfusion, and standard cold static storage (CS).MethodsPorcine kidneys underwent static CS for 23 hours followed by 1 hour of EVP using leukocyte-depleted blood at a mean temperature of 32°C or 37°C. After this, kidneys were reperfused with whole autologous blood at 37°C for 3 hours to assess renal function and injury. These were compared with a control group that underwent 24 hours CS.ResultsDuring EVP, kidneys perfused at 37°C had a higher level of renal blood flow and oxygen consumption compared with EVP at 32°C (P = 0.001, 0.002). During reperfusion, 32°C EVP kidneys had lower creatinine clearance and urine output than control (P = 0.023, 0.011) and a higher fractional excretion of sodium, serum potassium, and serum aspartate transaminase than 37°C EVP kidneys (P = 0.01, 0.023, 0.009).ConclusionsTubular and renal functions were better preserved by a near-physiological temperature of 37°C during 1 hour of EVP, when compared to EVP at 32°C or cold storage.

Clinical Case: About a Probable Case of Post-Transfusion Purpura in a Homozygous Sickle Cell

Alloimmunization to platelet antigens exposes to a serious immunological incident. We report a probable case of a post-transfusion purpura from homozygous sickle cell child alloimmunized against platelet antigen. We detail the challenges of alloantibody identification and transfusion management. These challenges are due to the lack of laboratory techniques for typing HLA and HPA system and the use of leukocyte-depleted (filtered) blood products.

Leukocyte-depleted erythrocyte transfusion associated with less ICU stay among pediatrics with cardiac surgery

Perioperative transfusion has adverse effects in patients undergoing cardiac surgery. The effect of leukocyte-depleted (LD) erythrocyte transfusion in pediatrics’ cardiac surgery was until now unknown. A retrospective cohort study was conducted among pediatric patients who were no more than 3 years old and transfused with red blood cells during an open-heart surgery. Investigations were made into mechanical ventilator treatment duration, length of stay in the intensive care unit (ICU) and 90-day survival. A total of 174 pediatric patients were included in our study. The average age was 21.90 months old and the average weight was 9.18 kg. There were 107 patients received non-leukocyte-depleted (NLD) red blood cell (RBC) transfusion and 67 patients received LD erythrocyte transfusion. No statistically significant differences were detected in the 90-day survival rates between the NLD group and the LD group. Statistically significant differences were detected in the time spent on the mechanical ventilator[(5.3 ± 2.0) d vs. (2.6 ± 1.0) d; P= 0.01] and the lengths of ICU stay [(9.4 ± 6.0) d vs. (5.6 ± 4.0) d; P=0.02] between the NLD group and the LD group. LD blood transfusion was associated with decreased length of stay in ICU and the decreased time on the mechanical ventilator in pediatric cardiac surgery.

Perioperative Transfusion of Leukocyte-depleted Blood Products in Contemporary Radical Cystectomy Cohort Does Not Adversely Impact Short-term Survival

To evaluate the effect of leukoreduced-only perioperative blood transfusion (PBT) and corresponding survival outcomes in a radical cystectomy cohort of patients. We analyzed data from 1026 patients who underwent radical cystectomy at our institution. PBT was defined as transfusion in the intraoperative or within the postoperative hospitalization period. Multivariable analyses using Cox proportional hazards were performed to measure the association between PBT, patient variables, and 3 primary end points: recurrence-free survival, disease-specific survival, and overall survival. Kaplan-Meier curves estimated survival times and were compared with log-rank test. Overall, of a total of 1026 patients, 341 (33.2%) received leukoreduced PBT. The median follow-up was 27.5 months. Transfused patients were more likely to be female, had higher estimated blood loss, lower preoperative hemoglobin, were more likely to have received neoadjuvant chemotherapy, or had undergone a continent urinary diversion. Higher pathologic tumor and nodal stage were observed more frequently in patients who received PBT. On multivariable analysis, PBT was not associated with worse recurrence-free survival, disease-specific survival, and overall survival (all P > .05). Kaplan-Meier curves did not show any significant differences (all P > .05) between the transfused and nontransfused groups. In addition, no differences were found in regard to timing of transfusion, that is, intraoperative vs postoperative, in distinct analysis. No significant association was found between leukoreduced PBT and worse survival outcomes at short-term follow-up in a contemporary cohort of cystectomy patients. Prospective long-term follow-up is warranted.

Perioperative transfusion of leukocyte depleted blood products in gastric cancer patients negatively influences oncologic outcome

The influence of perioperative transfusion (PT) on outcome following surgery for gastric cancer (GC) remains controversial, with randomized trials lacking and observational series confounded by patient risk factors. This analysis determines the association between reception of leukocyte-depleted blood products and post-operative survival for GC.Data from 610 patients who underwent curative surgery for GC in a German tertiary care clinic from 2001 to 2013 were included. Kaplan-Meier survival curves and Cox proportional hazards regression were applied to determine the association of PT and clinical and patient risk factors for overall and relapse-free survival. Propensity score analysis was performed to adjust for observational biases in reception of PT.Higher Union International Contre le Cancer/American Joint Committee on Cancer (UICC/AJCC)-stages (P <0.001), postoperative complications and severity according to the Clavien-Dindo (CD) classification (P <0.001), PT (P = 0.02), higher age (P <0.001), and neoadjuvant chemotherapy (P <0.001) were related to increased mortality rates. Higher UICC-stages (P <0.001), neoadjuvant chemotherapy (P <0.001), and type of surgery (P = 0.02) were independently associated with increased relapse rates. Patients were more likely to receive PT with higher age (P = 0.05), surgical extension to adjacent organs/structures (P = 0.002), tumor location (P = 0.003), and female gender (P = 0.03). In the adjusted propensity score weighted analysis, PT remained associated with an increased risk of death (hazard ratio (HR): 1.31, 95% CI: 1.01-1.69, P = 0.04).Because of the association of PT with negative influence on patient survival following resection for GC, risks from application of blood products should be weighed against the potential benefits.

Associations between the Transfusion of 1 and 2 Units of Leukocyte-depleted Red Blood Cells and Outcomes in Patients Undergoing Open Heart Valve Surgery

Associations between the Transfusion of 1 and 2 Units of Leukocyte-depleted Red Blood Cells and Outcomes in Patients Undergoing Open Heart Valve Surgery

Warm vs. cold perfusion techniques to rescue rodent liver grafts

A variety of liver perfusion techniques have been proposed to protect liver grafts prior to implantation. We compared hypothermic and normothermic oxygenated perfusion techniques in a rat liver transplant model, using higher risk grafts obtained after cardiac arrest (DCD). Rat livers were subjected to 30 or 60 min in situ warm ischemia, without application of heparin. Livers were excised and stored for 4 h at 4°C, mimicking DCD organ procurement, followed by conventional organ transport. In experimental groups, DCD liver grafts received a 4 h normothermic oxygenated perfusion through the portal vein and the hepatic artery instead of cold storage. The perfusate consisted of either full blood or leukocyte-depleted blood (normothermic groups). Other livers underwent hypothermic oxygenated perfusion (HOPE) for 1 h after warm ischemia and 4 h cold storage (HOPE group). Liver injury was assessed during machine perfusion and after isolated liver reperfusion, and by orthotopic liver transplantation (OLT). DCD livers, subjected to normothermic perfusion, disclosed reduced injury and improved survival compared to cold storage after limited warm ischemia of 30 min (70%; 7/10), but failed to protect from lethal injury in grafts exposed to 60 min warm ischemia (0%; 0/10). This finding was consistent with Kupffer and endothelial cell activation in cold stored and normothermic perfused livers. In contrast, HOPE protected from hepatocyte and non-parenchymal cell injury and led to 90% (9/10) and 63% (5/8) animal survival after 30 and 60 min of donor warm ischemia, respectively. This is the first evidence that HOPE is superior to normothermic oxygenated perfusion in a clinically relevant model through modulation of the innate immunity and endothelial cell activation.

Impact of Pre-Storage and Bedside Filtered Leukocyte-Depleted Blood Transfusions on Infective Morbidity after Colorectal Resection: A Single-Center Analysis of 437 Patients

Leukocyte-depleted blood transfusions were introduced to reduce transfusion-associated immunomodulation, but the clinical effects of different types of leukocyte depletion have been analyzed rarely. The aim of this survey was to analyze the clinical impact of pre-storage leukocyte-depleted blood transfusions (considered as pre-storage or bedside-filtered) on post-operative complications in patients undergoing elective or urgent colorectal resection. Data were collected retrospectively from the medical records of 437 consecutive patients who underwent colorectal resection from 2005 to 2010. All patients requiring transfusion received pre-storage or bedside-filtered leukocyte-depleted red blood cell concentrates according to availability at the blood bank. The outcomes were measured by the analysis of post-operative morbidity in patients receiving the different types of transfusions or having other potentially predictive risk factors. The overall morbidity rate, infective morbidity rate, and non-infective morbidity rate were, respectively, 35.6%, 28.1%, and 21.0%. Two hundred five patients (46.9%) received peri-operative transfusions. On multivariable analysis, leukocyte-depleted transfusion (odds ratio [OR] 3.33; 95% confidence interval [CI] 2.14-5.20; p<0.001) and both pre-storage (OR 2.82; 95% CI 1.73-4.59; p<0.001) and bedside-filtered (OR 4.69; 95% CI 2.54-8.67; p<0.001) transfusions were independent factors for post-operative morbidity. Prolonged operation (p=0.035), American Society of Anesthesiologists score≥3 points (p=0.023), diagnosis of cancer rather than benign disease (p=0.022), and urgent operation (p=0.020) were other independent predictors of post-operative complications. Patients transfused with bedside-filtered blood showed significantly higher rates of infective complications (51.4% vs. 31.8%; p=0.006), but not non-infectious complications (35.7% vs. 32.6; p=0.654) than patients who received pre-storage transfusions. Leukocyte-depleted blood transfusions and, in particular, bedside-filtered blood have a significant negative effect on infectious complications after colorectal resection.

Does leukocyte-depleted blood cardioplegia reduce myocardial reperfusion injury in cardiac surgery? A systematic review and meta-analysis

Blood cardioplegia in cardiac surgery contains leukocytes, which causes the inflammatory reaction and promotes myocardial reperfusion injury. The removal of leukocytes from the cardioplegia line, using specialized filters, has been proposed as one of the effective methods in attenuating the inflammatory response. We performed a two-level search to identify randomized, controlled trials concerning the effects of leukocyte-depleted blood cardioplegia on myocardial reperfusion injury. Sixteen studies, comprising 738 patients, met the selection criteria. There are significant reductions in creatinine kinase isoenzyme MB (CK-MB) during 4-8h postoperatively (SMD - 0.577; 95% CI -0.795 to -0.358; p=0.000), CK-MB peak (SMD - 0.713; 95% CI -1.027 to -0.400; p=0.000), troponin in the period of 4-8h postoperatively (SMD - 0.502; 95% CI -0.935 to -0.069; p=0.023), troponin peak (SMD - 0.826; 95% CI -1.373 to -0.279; p=0.003) and inotropic support (RR, 0.500; 95% CI 0.269 to 0.931; p=0.029). Leukocyte-depleted blood cardioplegia may reduce myocardial reperfusion injury in the early postoperative period, but there has been no evidence to support the clinically significant difference. Larger and more precise randomized control trials are needed to further elucidate the cardioprotective effects of cardioplegia leukofiltration.

Persufflation as a Means of Restoring the Function of Hearts Sourced from Donors after Circulatory Death

Introduction: Utilisation of hearts from Donors after Circulatory Death (DCD) could increase the donor pool and stem the decline in heart transplantation. Persufflation is a method of introducing oxygen into the organ during the cold preservation phase. This may offset the effects of warm ischaemia inflicted on the DCD heart, enabling a greater chance of functional recovery. Methods: Seventeen cross-Yorkshire Landrace pigs (divided into three groups) were euthanased humanely by Schedule-1 (intravenous administration of phenobarbitone) or exsanguination. The non-beating hearts were procured after being subjected to 10 - 29 minutes of warm ischaemia. All hearts underwent initial antegrade flush with AQIX® RS-I solution (a novel non-phosphate pH buffered preservation solution). Group I and II hearts were subjected to static cold storage (SCS). The Group III hearts were subjected to retrograde oxygen persufflation via the coronary sinus, at a pressure of 12mmHg, whilst the heart was immersed in cold AQIX® RS-I solution. 10-12 small holes were made in the myocardium, using a 21G needle, to create an outlet for excess oxygen. Reperfusion was performed on a Langendorff modification of Model 30 Functional Circulation circuit, using a mixture of heparinised, leukocyte-depleted blood and AQIX® RS-I solution. Drugs (adrenaline, calcium gluconate, dopamine) and DC cardioversion were used to initiate left ventricular activity. Results:[Figure 1]Discussion: DCD hearts subjected to preservation using coronary sinus oxygen persufflation can be successfully reanimated. This study compared persufflation with a retrospective control group (SCS). However, persufflation has demonstrated promise as a potential method for introducing oxygen into the heart during the cold preservation phase, with subsequent ability to achieve sustained reanimation.

Platelets induce endothelial tissue factor expression in a mouse model of acid-induced lung injury

Although the lung expresses procoagulant proteins under inflammatory conditions, underlying mechanisms remain unclear. Here, we addressed lung endothelial expression of tissue factor (TF), which initiates the coagulation cascade and expression of which signifies development of a procoagulant phenotype in the vasculature. To establish the model of acid-induced acute lung injury (ALI), we intranasally instilled anesthetized mice with saline or acid. Then 2 h later, we isolated pulmonary vascular cells for flow cytometry and confocal microscopy to detect the leukocyte antigen, CD45 and the endothelial markers VE-cadherin and von Willebrand factor (vWf). Acid increased both the number of vWf-expressing cells as well as TF and P-selectin expressions on these cells. All of these effects were markedly inhibited by treating mice with antiplatelet serum, suggesting the involvement of platelets. The increased expressions of TF, vWf, and P-selectin in response to acid also occurred in platelets. Moreover, the effects were replicated in endothelial cells derived from isolated, blood-perfused lungs. However, the effect was inhibited completely in lungs perfused with platelet-depleted and, to a lesser extent, with leukocyte-depleted blood. Acid injury increased endothelial expressions of the platelet proteins, CD41 and CD42b, providing evidence that platelet proteins were transferred to the vascular surface. Reactive oxygen species (ROS) were implicated in these responses, in that the endothelial and platelet protein expressions were inhibited. We conclude that acid-induced ALI causes NOX2-mediated ROS generation that activates platelets, which then generate a procoagulant endothelial surface.

Leukocyte-depleted blood transfusion is associated with decreased survival in resected early-stage lung cancer

Blood transfusion has been shown to have deleterious effect on lung cancer survival, but little data are available that assess whether leukocyte-depleted (LD) blood has a similar adverse effect. Our institution has been using LD red cells since 2001. We sought to determine whether LD blood has an effect on survival after resection of early-stage lung cancer. From a prospective database, we evaluated all patients with pathologic stage I non-small cell lung cancer. Patients receiving LD blood were compared with those receiving no transfusion. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis by Cox regression was used to identify independent risk factors affecting survival. From 2001 to 2009, 361 patients were evaluated; 63 received LD red cell cell transfusion and 298 received no transfusion. Median follow-up was 48 months. Disease-free survival (P < .001) and overall survival (P < .001) were worse in patients receiving LD blood. Stratifying for stage, disease-free survival continued to be worse with transfusion for stage IA (P = .002) and IB (P = .002). Similarly, overall survival continued to be worse with transfusion for stage IA (P < .001) and IB (P < .001). For disease-free and overall survival, univariate analysis revealed increased age, male gender, anemia, transfusion, and higher stage to be adverse factors, with transfusion and higher stage continuing to be significant adverse factors after multivariate analysis. Our data suggest that transfusion of LD blood is associated with a worse disease-free and overall survival in patients with resected stage I non-small cell lung cancer.

Prevalence of anti-CMV antibodies in blood donors in Ouagadougou (Burkina Faso)

The aim of our study was to investigate the prevalence of CMV antibodies among blood donors at a regional blood transfusion center in Ouagadougou. Blood collected from 115 donors was tested for specific anti-CMV antibodies as well as routine markers. The donors ranged in age from 18 to 53 years (mean: 28.78 ± 8.9 years), and 72.2% were men. In all, 4.3% were positive for HIV, 12.2% for HBs Ag, 2.6% for HCV, and 1.7% for syphilis. Nearly all donors (n=106, 92.2%) had CMV IgG antibodies, but only 12.2% (n=14) IgM antibodies, and all of the latter were also positive for IgG. CMV infection was not related to the donors' HIV status (p=0.66). The seroprevalence of CMV infection was not statistically related to gender, age or occupational status. There was no significant difference in the prevalence of any routine markers between donors positive and negative for CMV. The high rate of CMV antibodies indicates that CMV infection is widespread in Burkina Faso. Although it is thus unnecessary to test blood donors routinely for CMV, immunodepressed and other risk subjects should receive CMV-negative or leukocyte-depleted blood.

Transfusion of allogenic leukocyte-depleted packed red blood cells is associated with postoperative morbidity in patients undergoing oral and oropharyngeal cancer surgery

Evidence indicates that allogenic packed red blood cell transfusion results in the host's immunomodulation, and is associated with adverse clinical outcomes after surgery. The aim of this study was to test whether allogenic leukocyte-depleted blood transfusion represents a significant risk factor for postoperative morbidity after oral and oropharyngeal cancer surgery. A total of 142 patients, diagnosed for the first time with oral and oropharyngeal squamous cell carcinoma, and receiving neoadjuvant chemoradiotherapy followed by surgery between 2000 and 2008 were retrospectively included in this study. Univariate and multivariate logistic regression models were calculated to identify predictors of postoperative complications. We found a significantly higher complication rate in the group of transfused patients compared to patients not exposed to transfusion (complication rate of 84% and 39%, respectively, p<0.001). On multivariate analysis, the amount of packed red blood cells transfused (for 1-4 units transfused: adjusted OR, 2.59; 95% CI, 1.24-5.39; p=0.011; for more than >4 units transfused: adjusted OR, 5.29; 95% CI, 2.01-13.88; p=0.001) and Charlson's comorbidity score ≥1 (adjusted OR, 2.81; 95% CI, 1.38-5.70; p<0.004) were independently associated with the development of postoperative complications. Allogenic leukocyte-depleted blood transfusion is independently associated with increased postoperative complications in patients undergoing surgery for oral and oropharyngeal cancer. This association follows a dose-response relationship, as patients who received larger amounts of packed red blood cells showed a significant trend toward higher postoperative morbidity.

Effects of leukocyte-depleted allogeneic blood transfusion on perioperative cellular immunity in children

Objective To investigate the effects of leukocyte-depleted allogeneic blood transfusion on perioperafive cellular immunity in children.Methods Three hundred and fifty-nine ASA Ⅰ or Ⅱ children aged 3 month-14 yr,weighing 5-74 kg requiring allogeneic blood transfusion during operation were randomly divided into 2 groups:control group (group C,n =163) and leukocyte depletion group (group D,n =196).In group D allogeneic blood was filtered with a leukocyte filter before being transfused during operation.Blood samples were collected from peripheral vein before blood transfusion,and at 2 and 6 d after blood transfusion for determination of levels of CD3+,CD4+,CD8+,and CD56+ by flow cytometry.CD4+/CD8+ ratio was calculated.The volume of allogeneic blood transfused during operation,the duration of operation,postoperative drainage,antibiotics administration and hospital stay and incidence of postoperative infection were recorded.Results The levels of CD3+,CD4+,CD56+ and CD4+/CD8+ ratio were significantly increased at 6 d after blood transfusion while the duration of postoperative drainage,postoperative antibiotics administration and hospital stay and incidence of postoperative infection were significantly decreased in group D compared with group C.Conclusion Leukocyte-depleted allogeneic blood transfusion is helpful in improving the postoperative cellular immunity in children. Key words: Leukspheresis; Blood transfusion; Immunity, cellular; Child

Donor Heart Preservation in an Empty Beating State Under Mild Hypothermia

Cardiac surgery during an empty beating heart state has proven to be beneficial in myocardial protection. Based on this, we hypothesized that maintaining this state for donor heart preservation would have the same efficacy and a prolonged preservation period. Part 1: 12 pigs were divided into two groups (n = 6 per group). Donor hearts were preserved in group A by perfusion with leukocyte-depleted blood in the beating state, and in group B, in the traditional hypothermic static state with University of Wisconsin solution. After 8 hours, myocardial samples were obtained to detect myocardial edema, adenosine triphosphate, and ultrastructure. Part 2: 12 donor-recipient swine pairs were randomly allocated to either beating heart preservation with perfusion (group C) or traditional static preservation (group D). Donor hearts were stored for 8 hours after isolation, followed by implantation into recipient animals. Implanted hearts recovered for 120 minutes in an empty and beating state followed by 30 minutes in a working state, after which cardiac function was measured. After preservation, myocardial adenosine triphosphate levels in group A were significantly higher than in group B. However, myocardial water content was not significantly different between these two groups. The damage of myocardial ultrastructure in group A was slight compared with that of group B. The experimental transplant group C showed excellent heart function after implantation when compared with group D. Our study reveals greater effects of donor heart preservation in a beating state rather than simply with hypothermic storage in University of Wisconsin solution.

Effects of allogeneic leukocytes in blood transfusions during cardiac surgery on inflammatory mediators and postoperative complications*

To investigate whether the higher prevalence of postoperative complications in cardiac surgery after transfusion of leukocyte-containing red blood cells can be related to inflammatory mediators. Analysis of inflammatory markers interleukin-6, interleukin-10, interleukin-12, and procalcitonin in patients participating in a randomized trial comparing leukocyte-depleted with leukocyte-containing, buffy-coat-depleted red blood cells. Two university-affiliated hospitals in the Netherlands. A total of 346 patients undergoing cardiac valve surgery with a complete series of pre- and postoperative blood samples. There were no differences in the cytokines and procalcitonin concentrations between both study arms when the patients arrived in the intensive care unit. In subgroups, patients who received zero to three red blood cell transfusions showed similar cytokine concentrations in both study arms, whereas patients with > or = 4 red blood cell transfusions had significantly higher interleukin-6 concentrations in the leukocyte-containing, buffy-coat-depleted red blood cell group. Patients who developed postoperative infections and multiple organ dysfunction syndrome showed, respectively, increased concentrations of interleukin-6 and interleukin-12 in the leukocyte-containing, buffy-coat-depleted, red blood cell group. The interaction tests in these subgroups showed significantly different reaction patterns in the leukocyte-containing, buffy-coat-depleted red blood cell group compared with leukocyte-depleted red blood cell group for interleukin-6 and interleukin-12. Multivariate analysis showed a high interleukin-6 concentration with multiple organ dysfunction syndrome and both high interleukin-6 and interleukin-10 concentrations with hospital mortality. Allogeneic leukocyte-containing blood transfusions compared with leukocyte-depleted blood transfusions induce dose-dependent significantly higher concentrations of proinflammatory mediators in the immediate postoperative period after cardiac surgery. High concentrations of interleukin-6 are strong predictors for development of multiple organ dysfunction syndrome, whereas both interleukin-6 and interleukin-10 are associated with hospital mortality. These findings suggest that leukocyte-containing red blood cells interfere with the balance between postoperative proinflammatory response, which may further affect the development of complications after cardiac surgery.