Fresh Blood Transfusion Research Articles

Massive hemoperitoneum due to rupture of surface veins of a uterine leiomyoma

Rupture of veins on the surface of uterine leiomyoma is an extremely uncommon gynaecological cause of hemoperitoneum .It is a life threatening emergency. We report a case of massive intraperitoneal hemorrhage due to rupture of vessels on the surface of subserous leiomyoma.The patient underwent diagnostic laparoscopy followed by laparotomy and hysterectomy. She received 5 units of fresh blood transfusion and had smooth postoperative period. A differential diagnosis of rupture of surface vessel of leiomyoma should be considered, while dealing with a case of hemoperitoneum with pelvic mass.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

AbstractIn a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

Clinical response and transfusion reactions of sheep subjected to single homologous blood transfusion.

Studies in relation to blood conservation and responses to transfusion are scarce for ruminants. We evaluated the clinical manifestations of sheep that received a single homologous transfusion of whole blood, focusing on transfusion reactions. Eighteen adult sheep were subjected to a single phlebotomy to withdraw 40% of the total blood volume, which was placed into CPDA-1 bags and then divided into G0, animals that received fresh blood, and G15 and G35, animals that received blood stored for 15 or 35 days, respectively. Clinical observations were recorded throughout the transfusion, whereas heart rate, respiratory rate, and rectal temperature were assessed at the following times: 24 hours after phlebotomy and before transfusion; 30 minutes, six, twelve, 24, 48, 72, and 96 hours and eight and 16 days after transfusion. All groups presented transfusion reactions, among which hyperthermia was the most frequent (50% of animals). Tachycardia occurred most frequently in the G35 animals (50% of them). During transfusion G35 animals presented more clinical manifestation (P < 0.05). Transfusion of fresh or stored total blood improved the blood volume, but transfusion reactions occurred, demonstrating that a single transfusion of fresh or stored blood can cause inflammatory and febrile nonhemolytic transfusion reactions in sheep.

Plasma-free hemoglobin and microvascular response to fresh or old blood transfusion in septic patients

Free hemoglobin (fHb) can scavenge nitric oxide and induce vasoconstriction [1]. The fHb content may be higher in older blood bags. We studied whether old red blood cell (RBC) transfusion increases plasma fHb in septic patients and if this affects the microvascular response.

Resuscitation from hemorrhagic shock using polymerized hemoglobin compared to blood

The development of an alternative to blood transfusion to treat severe hemorrhage remains a challenge, especially in far forward scenarios when blood is not available. Hemoglobin level (Hb)–based oxygen (O2) carriers (HBOCs) were developed to address this need. Hemopure (HBOC-201, bovine Hb glutamer-250; OPK Biotech, Cambridge, MA), one such HBOC, has been approved for clinical use in South Africa and Russia. At the time of its approval, however, few studies aimed to understand Hemopure's function, administration, and adverse effects compared to blood. We used intravital microscopy to study the microcirculation hemodynamics (arteriolar and venular diameters and blood flow and functional capillary density [FCD]) and oxygenation implications of Hemopure administration at different Hb concentrations—4, 8, and 12 gHb/dL—compared to fresh blood transfusion during resuscitation from hemorrhagic shock. Experiments were performed in unanesthetized hamsters instrumented with a skinfold window chamber, subjected to hemorrhage (50% of the blood volume), followed by 1-hour hypovolemic shock and fluid resuscitation (50% of the shed volume). Our results show that fluid resuscitation with Hemopure or blood restored systemic and microvascular parameters. Microcirculation O2 delivery was directly correlated with Hemopure concentration, although increased vasoconstriction was as well. Functional capillary density reflected the balance between enhanced O2 transport and reduced blood flow: 12 gHb/dL of Hemopure and blood decreased FCD compared to the lower concentrations of Hemopure (P < .05). The balance between O2 transport and tissue perfusion can provide superior resuscitation from hemorrhagic shock compared to blood transfusion by using a low Hb concentration of HBOCs relative to blood.

Abstract 18776: Endothelial Function is Not Affected by Fresh or Storage-Aged Autologous Blood Transfusions in Healthy Individuals

Background: Red cells play a modulating role in nitric oxide (NO)-mediated signaling and hypoxic vasodilation that may be influenced by blood transfusions, particularly with storage-aged blood (pRBCs). We have shown that brachial artery endothelial function, measured as flow-mediated vasodilation (FMD) is adversely affected in patients receiving aged compared to fresh pRBCs. Here we investigated endothelial NO activity in healthy subjects receiving autologous pRBCs with the hypothesis that aged pRBCs will impair endothelial conductance vessel and microvascular function. Methods: Sixteen healthy participants (aged 31±10 years, 38% female) were transfused 1 unit of fresh (aged 3-7 days) and subsequently with storage-aged (35-42 days) autologous pRBCs. Endothelial function was measured using FMD and reactive hyperemia index (RHI), a measure of microvascular function, was measured using pulsatile arterial tonometry (Itamar Inc., n=7), before, 1 hour, and 24 hours after transfusion. Data were analyzed by repeated measures ANOVA. Results: Hemoglobin was similar before both transfusions (p=0.066) and increased by 1.02±1.0 g/dL (±SD) and 1.2±1.2 g/dL with fresh and storage-aged transfusions, respectively. The FMD before, 1 hr and 24 hr after transfusion of fresh pRBCs (7.8±6.9%, 8.2±4.8% and 6.9±4.3%) or stored pRBCs (7.1±5.5%, 7.4±4.7% and 8.5±4.9%) was similar,( p=0.45). The RHI before, 1 hr and 24 hr after transfusion of fresh pRBCs ( 2.45±0.23, 2.26±0.08 and 2.26±0.21) showed no significant changes, p=0.87 or stored pRBCs ( 2.25±0.67, 2.27±0.53 and 2.22±0.26, p=0.42). Conclusions: Vascular NO activity and microvascular dilatory capacity are not impaired by transfusion of fresh or storage-aged autologous pRBC in healthy individuals, unlike findings with allogeneic transfusions in patients. These differences suggest that the risks of aged blood transfusions are likely to be greater in patients with vascular disease who have underlying endothelial dysfunction.

Transfusion-Associated Graft Versus Host Disease in the Immunocompetent Patient

Transfusion associated-graft versus host disease (TA-GVHD) is a rare complication of blood transfusion. It carries a very high mortality rate. Although the phenomenon has been well described in immunocompromised patients, this review focuses on the immunocompetent host. Cases of TA-GVHD continue to be reported following a variety of surgical procedures, especially cardiac procedures requiring cardiopulmonary bypass. Additional risk factors for TA-GVHD include blood component transfusion in populations with limited genetic diversity, the use of directed donations from family members, and the transfusion of fresh blood. As there is no effective treatment, the focus is on prevention.

Transfusion of fresh but not old stored blood reduces infarct size and improves cardiac function after acute myocardial infarction in anemic rats*

We recently demonstrated that transfusion of fresh blood to 100 g/L hemoglobin in anemic animals offers cardioprotection after acute myocardial infarction. The objective of this study was to compare the cardioprotective effects of fresh vs. stored blood when transfused in anemic rats after acute myocardial infarction. Randomized animal study. University laboratory. Male Sprague-Dawley rats weighing 200-300 g. Myocardial infarction was induced by coronary artery ligation in 49 male Sprague-Dawley rats weighing 200-300 g, 38 of which were anemic (80-90 g/L) and 11 with normal hemoglobin levels. Anemic animals were randomized to receive fresh blood (within 4 hrs), stored blood (7 days), or no transfusion immediately after myocardial infarction. At 24 hrs after myocardial infarction, cardiac function, infarct size, and apoptosis were determined. Erythrocyte ATP, 2,3-DPG, hemoglobin, and free hemoglobin levels in the supernatant were determined. Transfusion with fresh but not stored blood significantly decreased infarct size and myocardial apoptosis in anemic rats when compared to anemic animals not undergoing transfusion. Cardiac function and survival were significantly improved in the anemic animals undergoing fresh blood transfusion compared to control anemic animals. Analysis of stored red blood cells showed reductions of intracellular ATP and 2,3-DPG levels and free hemoglobin was increased in the supernatant. The prolonged storage of blood negates the beneficial effects of fresh blood transfusion, which include reductions in infarct size and myocardial apoptosis, and improvements in cardiac function and short-term survival after acute myocardial infarction in this animal model.

Erythropoietin is equally effective as fresh-blood transfusion at reducing infarct size in anemic rats: Erratum

Erythropoietin is equally effective as fresh-blood transfusion at reducing infarct size in anemic rats: Erratum

Transfusion of Fresh but Not Stored Blood Reduces Infarct Size and Improves Cardiac Function Following Acute Myocardial Infarction In Anemic Rats

AbstractAbstract 661 Background:Anemia is a predictor of poor outcomes in acute myocardial infarction (MI) and may increase the degree of ischemia, resulting in greater tissue injury. The only existing therapeutic intervention used to acutely correct anemia is red blood cell (RBC) transfusion, although its effectiveness at improving outcomes in anemic subjects following MI remains controversial. We have previously shown that transfusion of fresh blood in anemic rats following MI decreased infarct size, and improved cardiac function and survival (Hu et al. Transfusion 2010; 50:243-251). However, it was not known if the transfusion of stored blood, which develops a series of chemical and corpuscular changes collectively known as the “storage lesion”, would be equally effective in this model. Experimental Design:Acute MI was induced by coronary artery ligation in 49 male Sprague-Dawley rats, 38 of which were made anemic (Hb = 80–90 g/L) using a combination of dietary iron deprivation and phlebotomy, and 11 with normal Hb levels. Rat blood was stored for 7 days in CPDA-1 to induce a storage lesion similar to the one seen in human blood stored under identical conditions for 28 days (d'Almeida et al. Transfusion Medicine 2000; 10:291-303). Anemic animals were randomly assigned to one of three groups: i) fresh blood transfusion (stored for <4 hours) to increase the Hb to 100 g/L, ii) transfused with stored blood to increase the Hb to 100 g/L, or iii) no transfusion. At 24 hours post-MI, infarct size, cardiac function and survival rates were determined. Results:A similar degree of left ventricular (LV) myocardial ischemia (area at risk) was induced in all groups (P=NS). In agreement with previous results, the infarct size to area at risk ratios were significantly increased in the anemic (Hb 80–90 g/L) animals compared to non-anemic MI controls, and transfusion of fresh blood to a target Hb level of 100 g/L after MI decreased infarct size (P<0.05) and improved both systolic (+dP/dtmax) and diastolic (−dP/dtmin) LV function compared to anemic animals (P<0.05). However, the transfusion of stored blood into anemic animals post-MI did not have these effects when compared to the group receiving fresh blood (P<0.05). Furthermore, survival was increased in anemic animals receiving fresh blood (9/11; P<0.05) but not stored blood (7/14; P=NS) compared to the non-transfused group (5/13). Conclusions:The prolonged storage of blood negates the beneficial effects of fresh blood transfusion, which include reductions in infarct size, and improvements in cardiac function and short-term survival following acute MI in this animal model.(This study was supported by the Canadian Institutes of Health Research, Canadian Blood Services and the Bayer Partnership Fund). Disclosures:No relevant conflicts of interest to declare.

Quality of Life Outcomes of the Age of Blood In Highly Transfusion Dependent Patients with Myelodysplasia: Prospective Randomized Controlled N-of-1 Studies

AbstractAbstract 4411 Introduction:Anemia is the most common objective manifestation of the myelodysplastic syndromes (MDS), and excessive fatigue is experienced in over 80% of patients. Transfusion is essential for the management of anemia in these patients. Past studies have investigated the age of transfused blood and its effect on outcome in various acute clinical settings such as critically ill, post-cardiac surgery, trauma, and brain injury patients. However, few studies have investigated the age of transfused blood in chronically transfused patients such as MDS and its impact on quality of life (QoL) and hemoglobin (Hb) levels in these populations. Methods:The aim of our study was to compare QoL outcomes between fresh (transfused within 7 days of donation) and standard issue (transfused between 8 to 42 days, mean 20.5 days locally) blood in highly transfusion dependent patients including those with MDS. The Functional Assessment Cancer Therapy Anemia subscale (FACT-An) was utilized for QoL assessment in a series of prospective “N-of-1” trials design. An “N-of-1” study was performed for each of the participants. Each participant was randomized to receive a total of four transfusions of fresh blood and four transfusions of standard issue blood. Randomization tables were created for each participant “N-of-1” study a priori. The participants, nurses and investigators were blinded to the age of blood administered. Prior to each transfusion, and again after 24 hours, participants completed the FACT-An survey. Post transfusion Hb levels were measured prior to a subsequent transfusion. For each FACT-An parameter and Hb level, mean results were derived for the four fresh blood transfusions and for the four standard blood transfusions. These were analyzed using an unpaired Student's t-test. Results:Twenty patients were enrolled into the study at the London Health Sciences Centre (LHSC), London, Ontario, Canada. Participants included 8 males and 12 females with a mean age of 64.5 years. There were a total of 13 MDS participants (5 males, 8 females) and seven participants (3 males, 4 females) with other diseases that required them to be transfusion dependent. At the time of abstract submission, 1 participant has completed his “N-of-1” study. For this one individual, analysis comparing the pooled results of the four fresh blood transfusions versus the pooled results of the four standard issue blood transfusions was done. No significant difference was seen between fresh blood transfusions versus standard blood transfusions for all of the FACT-An parameters and post-transfusion Hb levels. Conclusions:Improving QoL is an essential component in the management of chronic diseases such as the myelodysplastic syndromes. We have designed a series of “N-of-1” studies to detect a potential difference between fresh versus standard issue red blood cells. The preliminary data from a single participant who has completed this “N-of-1” study suggest that there is no significant difference in QoL measures and Hb levels. The study has fully enrolled and demonstrated the feasibility of this novel approach to evaluating the clinical benefits of transfusion. To our knowledge this is the first reported “N-of-1” study in transfusion. Disclosures:No relevant conflicts of interest to declare.

Guidelines on the use of irradiated blood components prepared by the British Committee for Standards in Haematology blood transfusion task force

Search terms included: Transfusion-associated graft-versus-host disease, Transfusion-associated graft-versus-host, TA-GvHD. The last guideline covering this topic was published in 1996 (British Committee for Standards in Haematology (BCSH) Blood Transfusion Task Force, 1996. The writing group produced the new draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology and Blood Transfusion Task Forces of the BCSH. The guideline was then reviewed by a sounding board of approximately 100 UK haematologists, the BCSH and the committee of the British Society for Haematology and amended, again by consensus. Criteria used to quote levels and grades of evidence are according to the GRADE system (Guyatt et al, 2006). Strong recommendations (grade 1, ‘recommended’) are made when there is confidence that the benefits either do or do not outweigh the harm and burden and costs of treatment. Where the magnitude of benefit or not is less certain a weaker grade 2 recommendation (‘suggested’) is made. Grade 1 recommendations can be applied uniformly to most patients whereas grade 2 recommendations require judicious application. The quality of evidence is graded as A (high quality randomized clinical trials), moderate (B) or low (C). This publication reports the key recommendations of the Writing Group. It is also accessible at http://www.bcshguide lines.com.

Erythropoietin is equally effective as fresh-blood transfusion at reducing infarct size in anemic rats

We recently demonstrated that transfusion of anemic animals up to 100 g/L hemoglobin with fresh blood protects the heart from ischemic injuries following myocardial infarction. Erythropoietin has cardioprotective effects independent of its erythropoietic activity. The objective of this study was to compare the cardioprotective effects of erythropoietin treatment to fresh-blood transfusion in anemic rats after acute myocardial infarction. Randomized animal study. University laboratory. Male Sprague-Dawley rats weighing 200-300 g. Myocardial infarction was induced by coronary artery ligation in 76 rats, 55 of which were anemic (80-90 g/L) and 21 of which had normal hemoglobin levels. Animals were randomized to erythropoietin (2000 units/kg), fresh-blood transfusion to 100 g/L hemoglobin, or saline-treatment groups immediately following myocardial infarction. At 24 hrs after myocardial infarction, cardiac function and infarct size were determined. Myocardial apoptosis was determined by caspase-3 activity and terminal deoxynucleotidyl transferase d-UTP nick end labeling (TUNEL) assay. Infarct size was significantly decreased in anemic rats treated with erythropoietin or blood transfusion compared to those in the saline-treatment group. Cardiac function, as measured by maximal positive and minimal negative first derivatives of left ventricular pressure, was better preserved in the normal hemoglobin groups and the erythropoietin- or transfusion-treated anemic animals compared to saline-treated anemic animals. Myocardial caspase-3 activity and TUNEL-positive nuclei were significantly increased in anemic rats but were decreased by erythropoietin treatment or red blood cell transfusion. Erythropoietin treatment is equally effective as fresh-blood transfusion in anemic rats after acute myocardial infarction at reducing infarct size, myocardial apoptosis, and improving cardiac function.

Effects of anemia and blood transfusion in acute myocardial infarction in rats

The optimal hemoglobin (Hb) level in acute myocardial infarction (MI) is unknown. The goal of this study was to determine the optimal Hb concentration in acute MI and whether transfusion of fresh blood to correct anemia reduces myocardial injury and improves outcome. Anemia was induced in rats by an iron-deficient diet and phlebotomy. MI was induced by left coronary artery ligation. Some rats received transfusion of fresh blood. Survival, hemodynamic measurements, and infarct size were determined 24 hours after MI. Reduction of Hb to 80 to 90 and 70 to 80 g/L decreased 24-hour survival after MI to 42 and 47%, respectively (p < 0.05). Infarct size was increased in both 70 to 80 and 80 to 90 g/L anemic groups compared to the normal Hb group (p < 0.05). Cardiac function was decreased in anemic groups after MI (p < 0.01). Transfusion of fresh blood to increase Hb from 80 to 90 g/L to 100 g/L decreased infarct size (p < 0.05) and improved cardiac function (p < 0.05), and a trend toward better survival (73%) was observed. Transfusion from 80 to 90 g/L Hb to 120 g/L Hb was associated with larger infarct size (p < 0.05), decreased cardiac function (p < 0.05), and no improvement in survival (47%, p = NS). Anemia increases infarct size and decreases cardiac function and survival in acute MI. Transfusion of anemic animals up to 100 g/L Hb with fresh blood reduces infarct size and improves cardiac function. However, transfusion to 120 g/L Hb did not demonstrate any additional benefit and was associated with larger infarcts.

External aortic compression device: The first aid for postpartum hemorrhage control

To evaluate the external aortic compression device (EACD) as a first aid to control postpartum hemorrhage (PPH). Three hundred women whose deliveries were complicated with PPH were recruited into a quasi-randomization study. Groups comprised 120 women each who had atonic PPH. The EACD was used together with traditional management in study women, while traditional management alone was used in control women. Outcome measures were maternal mortality, morbidity (hysterectomy), amount of blood transfusion (BT), uterotonic drugs and time to stop bleeding. Side effects of the EACD were assessed. Atonic PPH was defined as a blood loss of >or=500 mL from an atonic uterus with circulatory compromise within 24 hrs of childbirth. Controls were treated with i.v. access, nasal oxygen, fresh BT, uterine massage, El-Menia air inflated balloon and uterotonic drugs. Study women were treated using EACD together with conventional management. Time to stop bleeding was significantly shorter (36.8 +/- 23.4 vs 118.6 +/- 36.8 min) in study women than in control women (P < 0.001); 87.5% of study women, but no single woman in the control group had their bleeding stopped within the first 45 min of PPH onset. No morbidities or mortality among those who received EACD compared with control women, among who had five surgical hysterectomies and one mortality. The amount of BT units (302 vs 200), ergometrine ampoules (3.6 +/- 0.5 vs 2.5 +/- 0.8), syntocinon units (30.6 +/- 0.5 vs 20.5 +/- 0.8) and misoprostol tablets (6.7 +/- 1.8 vs 3.8 +/- 0.7) received were significantly more in the control group than in the study group (P < 0.001). Adverse effects of EACD were rarely observed. EACD is a cost-effective and easily applied maneuver that allows satisfactory management of PPH without maternal mortality or morbidity. It is of value in developing countries.

CT Findings of Gastrointestinal Stromal Tumor in Meckel’s Diverticulum - a Case Report

Although the small bowel constitutes about 75% of the gastrointestinal (GI) tract, primary tumors in it are relatively rare, making up only a small percentage of all GI neoplasms. Neoplasms of Meckel's diverticulum are rare and gastrointestinal stromal tumors are very uncommon malignant tumors occurring in this site. We report a case of a small-bowel tumor with an extremely rare histological type and uncommon location which was diagnosed on 64 MDCT scan and subsequently confirmed at surgery and histopathology. A 46-year-old male nonsmoker and nondiabetic presented to the emergency department with 3 massive gastrointestinal bleeding episodes in the form of melena. On examination, the patient was apyrexial and was having tachycardia and pallor with a blood pressure of 80/30mmHg. He had no past history of hematemesis or melena. The patient was resuscitated by 6 fresh blood transfusions and underwent abdominal x-ray and ultrasonography which were unremarkable. In 24 hours, the patient underwent three EGDs which failed to reveal any cause of bleeding from upper gut. Next day, colonoscopy was done which showed colon smeared with altered blood; however, no mucosal abnormality was visualized up to the ileocecal valve. In addition, however, blood was seen pouring out through the ileocecal valve and about 10cm of terminal ileum were filled with blood. No mucosal lesion was seen. On the second day in evening, the patient again had two massive bleeding episodes, again went into shock and four more blood transfusions were given to combat shock. The patient was send to the department of radiodiagnosis for CT scan which was done by Siemens Somotom Sensation 64 Multislice CT and showed a highly enhancing pelvic mass, exophytic, projecting from the small-gut wall, likely arising from a Meckel’s diverticulum (figures 1, 2 and 3). Figure 1 Figure 1: Axial MDCT image showing an exophytic, briskly enhancing pelvic mass arising eccentrically from the small gut. CT Findings of Gastrointestinal Stromal Tumor in Meckel’s Diverticulum a Case Report

This Month in Anesthesiology

Mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of donors' leukocytes, erythrocytes, and soluble factors. Two tumor models were used in rats to study the impact of blood transfusion on the host ability to clear circulating cancer cells and host survival rates. The potential deleterious characteristics of the transfusion were also studied. Blood transfusion, in conjunction with blood storage time, was found to be an independent and significant risk factor for cancer progression, and aged erythrocytes mediated the effects. In rats, transfusion of fresh blood is less harmful than transfusion of stored blood. These results have implications for cancer patients receiving erythrocyte transfusions. See the accompanying Editorial View on page 951 This study examined the effect of isoflurane on γ-aminobutyric acid (GABA) levels in pontine reticular formation and the effect of drugs that increase or decrease GABA levels in the pontine reticular formation in experimental animals. Compared with wakefulness, GABA levels were significantly decreased by isoflurane. Nipecotic acid increased GABA levels and increased isoflurane induction time, whereas 3-mercaptopropionic acid decreased GABA levels and decreased isoflurane induction time. These results indicate that decreasing rather than increasing pontine reticular formation GABA levels is one mechanism by which isoflurane causes loss of consciousness and altered cortical excitability. See the accompanying Editorial View on page 948 Using a new risk scale developed for children, the effect size was calculated for treatments recommended for the pediatric population in the new Guidelines for the Management of Postoperative Nausea and Vomiting. Six single-drug therapies and five combination treatments were analyzed for risk reduction. With single-agent therapy using the 5-hydroxytryptamine receptor antagonists or dexamethasone, a 50–60% relative risk reduction is expected. Droperidol offers only a 40% decrease. With the combinations of a 5-hydroxytryptamine receptor antagonist and dexamethasone, a relative risk reduction in vomiting of about 80% is expected.In the senescent heart, β-adrenergic responsiveness is altered in parallel with β1- and β2-adrenoceptor down-regulation. This study tested the hypothesis that the β3-adrenoceptor plays a role in β-adrenergic receptor dysfunction in the senescent heart. β-adrenergic responses were investigated in vivo using echocardiography and in vitro using isolated left ventricular papillary muscle in young adult and senescent rats. An impaired positive inotropic effect in parallel with β3-adrenoceptor up-regulation was confirmed in senescent hearts both in vivo and in vitro . In the senescent group, the positive inotropic effect of β-adrenergic agonists was partially restored by nitric oxide synthase inhibitors. This was not the case in the young adult group. These results indicate β3-adrenoceptor overexpression plays a role in the altered β-adrenergic response in senescent cardiomyopathy via the induction of nitric oxide. See the accompanying Editorial View on page 956 Supervision of anesthesia residents by an attending anesthesiologist is associated with a decreased incidence of complications during emergent intubations outside the operating room. See the accompanying Editorial View on page 945 Training for fiberoptic orotracheal intubation using a high-fidelity simulator was not different than training with a low-fidelity simulator.Desmopressin is associated with a significant reduction in transfusion of blood products.This review evaluates different methods for determination of sympathetic nervous system activity and describes its role in human neurohumoral circulatory control. The effects of general anesthesia on sympathetic nervous system activity and their relevance for clinical anesthesia are discussed.

Blood Transfusion Promotes Cancer Progression: A Critical Role for Aged Erythrocytes

In cancer patients, allogeneic blood transfusion is associated with poorer prognosis, but the independent effect of the transfusion is controversial. Moreover, mediating mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of donors' leukocytes, erythrocytes, and soluble factors. Two syngeneic tumor models were used in Fischer 344 rats, the MADB106 mammary adenocarcinoma and the CRNK-16 leukemia. Outcomes included host ability to clear circulating cancer cells, and host survival rates. The independent impact of blood transfusion was assessed, and potential deleterious characteristics of the transfusion were studied, including blood storage duration; the role of erythrocytes, leukocyte, and soluble factors; and the kinetics of the effects. Blood transfusion was found to be an independent and significant risk factor for cancer progression in both models, causing up to a fourfold increase in lung tumor retention and doubling mortality rates. Blood storage time was the critical determinant of these deleterious effects, regardless of whether the transfused blood was allogeneic or autogenic. Surprisingly, aged erythrocytes (9 days and older), rather than leukocytes or soluble factors, mediated the effects, which occurred in both operated and nonoperated animals. The effects of erythrocytes transfusion in the MADB106 model emerged immediately and dissipated within 24 h. In rats, transfusion of fresh blood is less harmful than transfusion of stored blood in the context of progressing malignancies. Further studies should address mediating mechanisms through which erythrocytes' storage duration can impact the rate of complications while treating malignant diseases and potentially other pathologies.

Effect of Anemia and Red Blood Cell Transfusion in Acute Myocardial Infarction.

Background: The optimal hemoglobin (Hb) in the setting of acute myocardial infarction (MI) is unknown. Anemia reduces the oxygen carrying capacity of blood and may theoretically exacerbate ischemia increasing myocardial injury. The benefit of transfusion to correct anemia in acute coronary syndromes is also controversial. The goal of this study was to determine the optimal Hb in the setting of acute MI and whether transfusion reduces myocardial injury and improves outcome.Experimental design: Ninety-two male Sprague-Dawley rats (170–190g) were divided into 8 groups: 1: Normal Hb, sham operation; 2: Normal Hb, MI; 3: Hb 80–90g/L, sham; 4: Hb 80–90g/L, MI; 5: Hb 70–80g/L, sham; 6: Hb 70–80g/L, MI; 7: Hb 80–90g/L, MI with transfusion to 100g/L; 8: Hb 80–90g/L, MI with transfusion to 120g/L. To determine the effect of blood transfusion, fresh blood was immediately transfused following MI. Induction of myocardial infarction was preformed by left coronary artery ligation. Sham-operated rats underwent the same surgical procedure without ligation. At 24 hours post-MI, rats were re-anaesthetized and hemodynamic measurements preformed. Area at risk and infarct size was measured by Evans blue and triphenyltetrazolium chloride, respectively.Results: In the normal Hb group (140–150g/L), survival following sham or MI surgery was 100%. Reduction of Hb to 80–90 and 70–80g/L significantly decreased survival post-MI to 42% and 47%, respectively. Survival was significantly improved after transfusion of fresh blood to raise the hemoglobin from 80–90g/L to 100g/L (P<0.05). However, there was no improvement in survival when Hb was raised by transfusion to 120g/L (P=NS). Twenty-four hours post-MI, the ischemic to non-ischemic left ventricle (LV) weight ratios were not significantly different between any groups indicating similar areas of myocardial ischemia among all groups (P=NS). However, the infarct size to area at risk ratios were significantly increased in both 70–80g/L and 80–90g/L groups compared to the normal Hb group (P<0.05). Transfusion from Hb 80–90g/L to 100g/L significantly decreased infarct size compared to the Hb 80–90g/L group (P<0.05). However, transfusion to Hb 120g/L resulted in a significantly larger infarct size compared to the Hb 100g/L transfused group (P<0.05). Cardiac function was determined at 24 hours post-MI. Heart rate, MAP, LVSP and LVEDP were not significantly different among all groups but anemic groups 80–90 and 70–80g/L showed a significant decrease in LV +dP/dtmax and −dP/dtmin in both sham and MI rats (P<0.01) with the most significant decrease noted in MI rats compared to sham operated rats (P<0.05). Blood transfusion post-MI from a Hb 80–90 to 100g/L significantly improved LV +dP/dtmax (P<0.05). Transfusion to Hb 120g/L did not result in any further improvement in cardiac function.Conclusions: In the setting of acute MI, anemia increased mortality and infarct size compared to non-anemic controls. At 24 hours post-MI, anemia also impaired cardiac function. Transfusion of anemic animals up to a Hb of 100g/L with fresh RBCs reduced mortality and infarct size and improved cardiac function. However, transfusion to a Hb of 120g/L did not demonstrate any additional benefit and was associated with larger infarcts.

Effects of fresh versus banked blood transfusions on microcirculatory hemodynamics and tissue oxygenation in the rat cremaster model

Blood transfusion is recommended to prevent the harmful effects of tissue hypoxia. Whether transfusion alleviates hypoxia at the microcirculatory level is unknown. The objective of this study was to determine whether the effects of fresh blood transfusion on microcirculatory hemodynamics after blood loss are preferable to the effects of banked blood transfusion. Intravital microcirculatory hemodynamics was observed in the rat cremaster muscle flap by observers who were not blinded. Lewis rats were divided into 6 groups (8 rats per group): (1) untreated control; (2) blood withdrawal only (1 mL); (3) blood withdrawal and transfusion of rat fresh blood (1 mL); (4) blood withdrawal and transfusion with 1-day rat banked blood (1 mL); (5) blood withdrawal and transfusion with 1-week rat banked blood (1 mL); and (6) blood withdrawal and transfusion with 2-week rat banked blood (1 mL). Red blood cell velocity, blood flow, vessel diameter, functional capillary perfusion, red blood cell deformability, leukocytes (granulocytes and lymphocytes), and tissue oxygenation levels were monitored before transfusion and for 5 hours afterward. Histology was performed to evaluate tissue inflammation (hematoxylin and eosin [H&E] stain and myeloperoxidase [MPO] immunoassay) and hypoxia (Hypoxyprobe assay). Fresh- and banked blood-transfused groups did not differ in vessel diameters or red blood cell velocities. Functional capillary density was greater in the fresh blood group when compared to 1- and 2-week banked blood-transfused groups. The overall number of granulocytes (rolling, sticking, and transmigrated) was greater in all groups after transfusion (P < .001). Rats transfused with banked blood had a greater number of rolling lymphocytes and more inflammation. Tissue oxygenation levels were improved after fresh blood transfusion in comparison to banked blood (9.5 mm Hg vs 8 mm Hg, P = .02). Fresh blood transfusion is more effective in relieving effects of microcirculatory hypoxia. Banked blood, in particular 2-week stored blood, has limited capacity of improving tissue oxygenation.