Oxygen-carrying Capacity Of Blood Research Articles

Risks of Anemia in Cardiac Surgery Patients.

Anemia is an common condition in patients undergoing cardiac surgery, and it is often present in one quarter to half of patients at admission. Several studies have indicated that anemia is a major risk factor for worse outcomes, including increased risk of mortality and major morbidity and prolonged hospitalization. Anemia is a leading reason for use of allogeneic blood transfusions. Harmful effects of anemia are often attributed to the reduced oxygen carrying capacity of blood, reduced viscosity and the resulting impaired rheologic characteristics of blood, underlying comorbidities, and the side effects of treatments given for anemia, namely, allogeneic blood transfusions. Patients undergoing cardiac surgery may be at increased risk of anemia given the often-existing cardiac comorbidities and the negative impacts of cardiopulmonary bypass. However, whether less restrictive transfusion practices are justified in patients undergoing cardiac surgery is still a matter of debate. The prevalence of anemia often increases during hospital stay, and it can persist for a long time beyond hospital discharge. Given the associated risks and available management strategies, clinicians should remain vigilant to detect and treat anemia throughout the course of care for patients undergoing cardiac surgery.

Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training.

It remains unclear whether improvements in peak oxygen uptake (V̇(O2peak)) following endurance training (ET) are primarily determined by central and/or peripheral adaptations. Herein, we tested the hypothesis that the improvement in V̇(O2peak) following 6 weeks of ET is mainly determined by haematological rather than skeletal muscle adaptations. Sixteen untrained healthy male volunteers (age = 25 ± 4 years, V̇(O2peak) = 3.5 ± 0.5 l min(-1)) underwent supervised ET (6 weeks, 3-4 sessions per week). V̇(O2peak), peak cardiac output (Q̇(peak)), haemoglobin mass (Hb(mass)) and blood volumes were assessed prior to and following ET. Skeletal muscle biopsies were analysed for mitochondrial volume density (Mito(VD)), capillarity, fibre types and respiratory capacity (OXPHOS). After the post-ET assessment, red blood cell volume (RBCV) was re-established at the pre-ET level by phlebotomy and V̇(O2peak) and Q̇(peak) were measured again. We speculated that the contribution of skeletal muscle adaptations to the ET-induced increase in V̇(O2peak) would be revealed when controlling for haematological adaptations. V̇(O2peak) and Q̇(peak) were increased (P < 0.05) following ET (9 ± 8 and 7 ± 6%, respectively) and decreased (P < 0.05) after phlebotomy (-7 ± 7 and -10 ± 7%). RBCV, plasma volume and Hb(mass) all increased (P < 0.05) after ET (8 ± 4, 4 ± 6 and 6 ± 5%). As for skeletal muscle adaptations, capillary-to-fibre ratio and total Mito(VD) increased (P < 0.05) following ET (18 ± 16 and 43 ± 30%), but OXPHOS remained unaltered. Through stepwise multiple regression analysis, Q̇(peak), RBCV and Hb(mass) were found to be independent predictors of V̇(O2peak). In conclusion, the improvement in V̇(O2peak) following 6 weeks of ET is primarily attributed to increases in Q̇(peak) and oxygen-carrying capacity of blood in untrained healthy young subjects.

Cyanotic congenital heart disease (CCHD): focus on hypoxemia, secondary erythrocytosis, and coagulation alterations.

Children with cyanotic congenital heart disease (CCHD) have complex alterations in their whole blood composition and coagulation profile due to long-standing hypoxemia. Secondary erythrocytosis is an associated physiological response intended to increase circulating red blood cells and oxygen carrying capacity. However, this response is frequently offset by an increase in whole blood viscosity that paradoxically reduces blood flow and tissue perfusion. In addition, the accompanying reduction in plasma volume leads to significant deficiencies in multiple coagulation proteins including platelets, fibrinogen and other clotting factors. On the one hand, these patients may suffer from severe hyperviscosity and subclinical 'sludging' in the peripheral vasculature with an increased risk of thrombosis. On the other hand, they are at an increased risk for postoperative hemorrhage due to a complex derangement in their hemostatic profile. Anesthesiologists caring for children with CCHD and secondary erythrocytosis need to understand the pathophysiology of these alterations and be aware of available strategies that lessen the risk of bleeding and/or thrombosis. The aim of this review is to provide an updated analysis of the systemic effects of long-standing hypoxemia in children with primary congenital heart disease with a specific focus on secondary erythrocytosis and hemostasis.

Supra-plasma expanders: the future of treating blood loss and anemia without red cell transfusions?

Oxygen delivery capacity during profoundly anemic conditions depends on blood's oxygen-carrying capacity and cardiac output. Oxygen-carrying blood substitutes and blood transfusion augment oxygen-carrying capacity, but both have given rise to safety concerns, and their efficacy remains unresolved. Anemia decreases oxygen-carrying capacity and blood viscosity. Present studies show that correcting the decrease of blood viscosity by increasing plasma viscosity with newly developed plasma expanders significantly improves tissue perfusion. These new plasma expanders promote tissue perfusion, increasing oxygen delivery capacity without increasing blood oxygen-carrying capacity, thus treating the effects of anemia while avoiding the transfusion of blood.

Study on the selection of laser wavelengths in the intravascular low-level laser irradiation therapy.

According to the absorption spectra of blood and hemoglobin, a photon-bond energy formula is established using physical methods and the effects on hemoglobin of low-level laser at different wavelengths are analyzed. The results show that lasers with the peak wavelengths of 200∼240, 275, and 342 nm in the whole blood absorption spectra curve are easy to destroy protein molecules and then lead to hemoglobin lose biological activity. While lasers with wavelengths longer than 800 nm will reduce the oxygen carrying capacity of blood, only lasers with wavelengths between 630 and 670 nm have the best efficacy.

Cerebral Blood Flow and Metabolic Correlates of Near Infrared Spectroscopy in Patients with Sickle Cell Disease

Introduction Tissue oxygen index (TOI), by near Infrared Spectroscopy (NIRS), is a valuable tool for noninvasive, indirect measurement of oxygen supply-demand balance. Cerebral TOI is decreased in sickle cell disease (SCD), and correlates with disease severity. Previous work suggests that cerebral TOI is inversely correlated with hemoglobin S level and chronic transfusion therapy restores TOI to normal values. Nahavandi et al. have proposed that low cerebral TOI in SCD disease can be attributed to impaired oxygen delivery and/or carrying capacity of sickle blood. Unfortunately, the specificity of cerebral TOI is still an area of active debate. In order to elucidate these mechanisms we measured global cerebral blood flow (CBF),arterial oxygen content (CaO2), oxygen delivery (DO2), arterial and venous oxygen saturation (SaO2 and SvO2) and oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in 12 healthy controls and 15 SCD patients using magnetic resonance imaging (MRI).Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Fifteen patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. MRI compatible NIRS probes were placed on the forehead and TOI was recorded throughout the entire MRI examination. SaO2 was measured via peripheral pulse oximetery. Phase Contrast (PC) of the carotid and vertebral arteries was used to measure global CBF. T2 Relaxation Under Spin Tagging (TRUST) was used to measured T2 relaxation of blood within the sagittal sinus. T2 relaxation was converted to SvO2 via calibration curves. Blood draw for hemoglobin and electrophoresis was performed. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month.Results Table 1 summarizes the relationship between cerebral TOI, age, laboratory values, and hemodynamic variables. Surprisingly, TOI was independent of indices of oxygen supply (SaO2, CBF, oxygen delivery) and oxygen demand (CMRO2); cerebral venous saturation and OEF were the only hemodynamic correlate of TOI. Total hemoglobin and percent sickle hemoglobin were equally and independently correlated with TOI with a combined r2 of 0.59 on multivariate regression (p<0.0001).Discussion This represents the first study comparing TOI to direct measurements of cerebral oxygen supply and consumption in SCD patients. We demonstrate that TOI tracks SvO2 and OEF, suggesting that it is weighted toward venous vascular beds. The relationship of TOI and HbS% has been previously described and could either shifting of the oxygen dissociation curve or mechanical disruption of microvascular integrity. TOI’s strong dependence on total hemoglobin (after correction for HbS%) is particularly startling given its independence with oxygen delivery, suggesting that total hemoglobin is acting as a surrogate marker of microvascular disease severity in SCD patients. TableParameterR2pAge (Years)0.0127nsHemoglobin (gm/dl)0.295<0.05Hemoglobin S %0.229<0.05WBC (103/uL)0.0020nsCBF ml/100g/min0.018nsSaO2 (%)0.034nsO2 delivery0.071nsSvO2 (%)0.290<0.05OEF (%)0.238<0.05CMR020.112ns DisclosuresCoates:novartis: Honoraria, Speakers Bureau; shire: Consultancy, Honoraria; apo pharma: Consultancy, Honoraria, Speakers Bureau; acceleron: Consultancy, Honoraria.

Evidence and triggers for the transfusion of blood and blood products.

Allogeneic red cell transfusion is a commonly used treatment to improve the oxygen carrying capacity of blood during the peri-operative period. Increasing arterial oxygen content by increasing haemoglobin does not necessarily increase tissue oxygen delivery or uptake. Although the evidence-base for red cell transfusion practice is incomplete, randomised studies across a range of clinical settings, including surgery, consistently support the restrictive use of red cells, with no evidence of benefit for maintaining patients at higher haemoglobin thresholds (liberal strategy). A recent meta-analysis of 7593 patients concluded that a restrictive transfusion strategy was associated with a reduced risk of healthcare-associated infections (pneumonia, mediastinitis, wound infection, sepsis) when compared with a liberal transfusion strategy. The degree to which the optimal haemoglobin concentration or transfusion trigger should be modified for patients with additional specific risk factors (e.g. ischaemic heart disease), remains less clear and requires further research. Although most clinical practice guidelines recommend restrictive use of red cells, and many blood transfusion services have seen marked falls in overall usage of red cells, the use of other blood components such as fresh frozen plasma, platelets, and cryoprecipitate has risen. In clinical practice, administration of fresh frozen plasma is usually guided by laboratory tests of coagulation, mainly prothrombin time, international normalised ratio and activated partial thromboplastin time, but the predictive value of these tests to predict bleeding is poor.

Blood – the most important humour?*

Blood – the most important humour?*

Altered burst swimming in rainbow trout Oncorhynchus mykiss exposed to natural and synthetic oestrogens.

Juvenile rainbow trout Oncorhynchus mykiss were exposed to two concentrations each of 17β-oestradiol (E2; natural oestrogen hormone) or 17α-ethinyl oestradiol (EE2; a potent synthetic oestrogen hormone) to evaluate their potential effects on burst-swimming performance. In each of six successive burst-swimming assays, burst-swimming speed (Uburst ) was lower in fish exposed to 0.5 and 1 µg l(-1) E2 and EE2 for four days compared with control fish. A practice swim (2 days prior to exposure initiation) in control fish elevated initial Uburst values, but this training effect was not evident in the 1 µg l(-1) EE2-exposed fish. Several potential oestrogen-mediated mechanisms for Uburst reductions were investigated, including effects on metabolic products, osmoregulation and blood oxygen-carrying capacity. Prior to burst-swimming trials, fish exposed to E2 and EE2 for 4 days had significantly reduced erythrocyte numbers and lower plasma glucose concentrations. After six repeated burst-swimming trials, plasma glucose, lactate and creatinine concentrations were not significantly different among treatment groups; however, plasma Cl(-) concentrations were significantly reduced in E2- and EE2-treated fish. In summary, E2 and EE2 exposure altered oxygen-carrying capacity ([erythrocytes]) and an osmoregulatory-related variable ([Cl(-) ]), effects that may underlie reductions in burst-swimming speed, which will have implications for fish performance in the wild.

Vitamin D deficiency and low hemoglobin level as risk factors for severity of acute lower respiratory tract infections in Egyptian children: A case-control study

ObjectiveAcute lower respiratory tract infection (ALRTI) is an important cause of morbidity in the developed world, and both morbidity and mortality in the developing world. Vitamin D has a major role in both acquired and innate immunity. Anemic children have less oxygen carrying capacity of blood. This study was done to determine the relation between vitamin D deficiency, anemia and the severity of ALRTIs in hospitalized children. MethodsThis study included 96 hospitalized infants with ALRTI, 48 diagnosed with pneumonia and 48 with bronchiolitis. Mean age was 10.67±3.143months. Matched age and sex infants with no respiratory illness were included. Serum 25 hydroxy vitamin D was measured in all cases and controls by Radio-immune assay. Hemoglobin level was measured by Coulter. ResultsVitamin D deficiency and low hemoglobin level were positively correlated with the severity of ALRTIs (r=0.798 and P=0.001) and (r=0.708, P=0.028), respectively. Low vitamin D level was significantly correlated with low hemoglobin level (r=0.708, P=0.028). ConclusionVitamin D deficiency was associated with severity of ALRTIs. Low hemoglobin level was more prevalent in those children. Improving the nutritional status in children by preventing vitamin D deficiency and low hemoglobin might influence the outcome of children with ALRTI.

Chapter Seven - Nitric Oxide and Hypoxia Signaling

Nitric oxide (NO) production is catalyzed by three distinct enzymes, namely, neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). The production of NO by vascular endothelium relies mainly on eNOS. Curiously, iNOS and nNOS also are relevant for vascular NO production in certain settings. By relaxing vascular smooth muscle, the classical view is that NO participates in O2 homeostasis by increasing local blood flow and O2 delivery. It is now appreciated that NO has an even more fundamental role in cellular oxygen sensing at the cellular and physiological level. A key component of cellular oxygen sensing is the hypoxia-inducible factor (HIF) that activates a transcriptional program to promote cellular survival under conditions of inadequate oxygen supply. Important new insights demonstrate that HIF protein is stabilized by two parallel pathways: (1) a decrease in the O2-dependent prolyl hydroxylation of HIF and (2) NO-dependent S-nitrosylation of HIF pathway components including HIF-α. The need for these two complementary pathways to HIF activation arises because decreased oxygen delivery can occur not only by decreased ambient oxygen but also by decreased blood oxygen-carrying capacity, as with anemia. In turn, NO production is tightly linked to O2 homeostasis. O2 is a key substrate for the generation of NO and impacts the enzymatic activity and expression of the enzymes that catalyze the production of NO, the nitric oxide synthases. These relationships manifest in a variety of clinical settings ranging from the unique situation of humans living in hypoxic environments at high altitudes to the common scenario of anemia and the use of therapeutics that can bind or release NO.

Hypoxia effects on gill surface area and blood oxygen-carrying capacity of the Atlantic stingray, Dasyatis sabina

Atlantic stingrays, Dasyatis sabina, are common residents of shallow-water seagrass habitats that experience natural cycles of severe hypoxia during summer months. We hypothesized that stingrays exposed to hypoxic episodes would improve their hypoxia tolerance by increasing branchial surface area and altering blood oxygen-carrying capacity. To this end, we compared critical oxygen minimum, gill morphology, and hemoglobin/hematocrit levels in a control group of Atlantic stingrays held at continuous oxygen saturations of 80-90% (≥5.5 mg/l), to treatment groups exposed to a 7-h hypoxic interval at 55% (~4.0 mg/l), or 30% oxygen saturation (~2.0 mg/l). Stingrays in hypoxic treatment groups significantly improved their hypoxia tolerance. Critical oxygen minimum values fell from 0.7 ± 0.11 mg/l in control fish to 0.4 ± 0.05 and 0.4 ± 0.06 mg/l in the 55 and 30% saturation treatment groups, respectively. Mass-specific gill surface area between control fish and the 30% saturation treatment group increased by 1.7-fold, from 85 to 142 mm(2)/g. Although stingrays did not show an increase in hematocrit or hemoglobin levels, production of more efficient hemoglobin isoforms could not be ruled out. An increase in hypoxia tolerance allows Atlantic stingrays to forage for longer times and across a wide range of hypoxic habitats that are less accessible to predators and competitors.

Rebuttal to Pro Statements

High-altitude (HA) natives show distinctive physical and functional characteristics that give them an advantage over lowlanders at HA. These advantages are not confined to the cardio-respiratory or hematological systems, as they include indeed the whole organism, and must be reflected in different regions of the brain. In this regard, the reduced cerebrovascular reactivity in HA natives reported by Yan et al., (2011a) was particularly manifested among brain regions involved in cerebral modulation of respiration. Hochachka and co-workers have shown that lower regionby-region brain glucose metabolic rates in HA Quechuas compared to lowlanders may be the result of a defense adaptation against chronic hypoxia (Hochachka et al., 1994). Also, the psychomotor slowing observed in European, Native American, and African altitude groups is proposed to be an adaptive rather than a deficient trait (Hogan et al., 2010). In addition, the very scarce studies in spatial working memory matched by age, gender ratio, educational level, and ancestral lines, show equal accuracy response in HA compared to SL groups, but with more variability in reaction time; and the same activation patterns in their neural pathways (Yan et al., 2011b). Evaluation of the effects of altitude on mood, behavior profile, and cognitive function is complicated by differences between studies, including the specific methods of measurement and type of participants, which explain why there are so few. Since most of the systematic research in these areas has been conducted in exposure to experimental acute or moderate-lasting hypoxia, the results should not be generalized to altitude settings. On the physical side, besides being able to run a complete marathon at 4300 m, superior pulmonary gas-exchange and acidbase state in HA natives was evidenced by Wagner et al. (2002) and Lundby et al. (2004), who compared lowlanders acclimatized to 5260 m with HA natives at the same altitude in Bolivia. During exercise, HA natives showed smaller alveolar-arterial Po2 difference, 40% higher O2-diffusing capacity, and greater lactic acid buffering. In addition, despite lower anaerobic capacities, HA natives were capable of calf muscle work rates equal to those of highly-trained power athletes (Matheson et al., 1991). Also, aerobic exercise capacity of chronic mountain sickness patients with significant erythrocytosis is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of blood and pulmonary O2-diffusion (Groepenhoff et al., 2012). Even though in his later publication (Barcroft, 1925), concluded that acclimatization to HA does not exist, generalizing this concept even to HA natives, Barcroft was very impressed by the physical capacities of the Peruvian Andean natives, and this was certainly an accurate feeling.

WATER AS A PHYSIOLOGICAL LIMITATION TO FLIGHT DURATION IN MIGRATING BIRDS: THE IMPORTANCE OF EXHALED AIR TEMPERATURE AND OXYGEN EXTRACTION

ABSTRACT We used a computer model that calculates net water loss of flying birds as a function of the bird's morphological and physiological characteristics and of ambient meteorological conditions. Sensitivity analysis indicated that, of the model input variables, oxygen extraction and exhaled air temperature have the largest effect on dehydration during flight. Oxygen extraction affects dehydration rate through its effect on ventilatory volume and, thus, on respiratory water loss. Exhaled air temperature influences dehydration rate by modulating the recondensation of water vapor in exhaled air on the walls of the respiratory passages. This might save water that would otherwise be lost. Both variables depend on other factors, such as the structure of the air passages, the flow dynamics of respiratory air, the neural control of blood flow to the mucosal surfaces of the anterior respiratory tract, and the blood oxygen-carrying capacity.

A Numerical Method for Structured Population Equations Modeling Control of Erythropoiesis

Population equations with more than one structuring attribute play an essential role in modeling cell populations important for the process of erythropoiesis. Attributes in this case are cell age, iron content of cells and number of transferrin receptors on the cell membrane. The system is controlled via a feedback control using the oxygen carrying capacity of blood (which is determined by the number of red blood cells) as input for the controller and erythropoietin secreted by the kidneys as control for the system. The numerical algorithm is based on Trotter-Kato type approximations of the system state by system states of high order ordinary differential equations on finite dimensional subspaces of the state space of the system. These finite dimensional subspaces are generated by Legendre polynomials.

Prevention of Pulmonary Hypertension and Suppression of Pulmonary Inflammation and Platelet Activation by Breathing Nitric Oxide in Lambs Subjected to Hemorrhagic Shock and Autologous Stored Blood Transfusion

AbstractAbstract 841 Introduction:Transfusion of red blood cells (RBCs) restores the oxygen carrying capacity of blood after hemorrhagic shock (HS). During extended storage, RBCs undergo functional changes, altering their physiological properties. Recent studies have suggested that transfusion of RBCs stored for prolonged periods of time is associated with increased morbidity and mortality in severely hemorrhaged patients.Our group has reported a model for autologous transfusion of stored RBCs in lambs and observed that transfusion of RBCs stored for 40 days transiently increased pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) in healthy lambs. We hypothesized that HS would sensitize lambs to the adverse effects of stored RBC transfusion, inducing severe pulmonary vasoconstriction, inflammation, and platelet activation. We further hypothesized that inhalation of 80 ppm nitric oxide (NO) during and after transfusion of stored RBCs would prevent pulmonary vasoconstriction and reduce pulmonary inflammation and platelet activation. Methods:We studied 3 to 4 month old Polypay lambs weighing 31±1 kg (all data mean±SEM). A tracheostomy and carotid and pulmonary artery catheters were placed under brief isoflurane anesthesia. Lambs were subjected to class 4 HS by withdrawing 50% of their blood volume. Mean arterial pressure was maintained at 50 mmHg for 2 h. Animals were then resuscitated over 1 h with 600 ml packed RBCs (hematocrit 55–60%) and an equal volume of lactated Ringer’s solution. One group of lambs (n=6) was resuscitated with the RBCs withdrawn to induce HS (fresh red blood cells, FRBCs). A second group of lambs (n=6) received autologous, leukoreduced RBCs stored in AS-1 additive solution for 39±2 days (stored red blood cells, SRBCs). An additional group of lambs receiving SRBCs (n=5) inhaled 80 ppm NO during and for 21 h after transfusion. Hemodynamic parameters were measured continuously for 24 h.Plasma hemoglobin concentrations were determined before and after transfusion using spectral deconvolution. Myeloperoxidase enzyme activity was measured in lung tissue samples harvested 21 h after the end of transfusion.Platelets were isolated from blood withdrawn before induction and immediately after resuscitation of HS. Platelet activation was assessed by measuring the number of P-selectin (CD62P)-expressing platelets with flow cytometry, both in naïve platelets and in platelets stimulated with increasing concentrations of adenosine diphosphate (ADP) ex vivo. Results:At the end of transfusion, PVR (253±43 vs. 104±5 dyn·s·cm−5, p=0.01) and mean PAP (24±4 vs. 14±2 mmHg, p<0.001) were higher in lambs transfused with SRBCs than in those transfused with FRBCs. Concurrent inhalation of NO completely prevented the increase of PVR (102±10 dyn·s·cm−5) and PAP (13±1 mmHg) induced by transfusing SRBCs. PAP correlated with peak plasma hemoglobin concentrations (R2=0.61, p=0.003). Two of the 6 lambs transfused with SRBCs developed severe systemic hypoxemia and pulmonary edema, whereas none of the lambs resuscitated with FRBCs or SRBCs during concurrent inhalation of NO developed hypoxemia or symptoms of respiratory compromise.Pulmonary myeloperoxidase enzyme activity of lambs transfused with SRBCs (11±2 U/g) was higher than that of lambs resuscitated with FRBCs (4±1 U/g, p=0.007), but was not elevated when animals breathed NO (8±1 U/g, p=0.09).There was no difference in the percentage of CD62P-expressing platelets after resuscitation of HS with either FRBCs or SRBCs (1.4±0.3 vs. 1.7±0.3 %, p=0.25). However, when stimulated with increasing concentrations of ADP, more platelets from lambs transfused with SRBCs expressed CD62P than those from lambs transfused with FRBCs. This increase in CD62P-expressing platelets after transfusion of SRBCs was attenuated by breathing NO. Conclusions:Hemorrhagic shock sensitizes lambs to the transfusion of stored autologous RBCs. Resuscitation of 6 lambs with severe HS by transfusion of SRBCs caused marked pulmonary vasoconstriction and inflammation, as well as severe hypoxemia and pulmonary edema in 2 lambs. Inhalation of NO completely prevented pulmonary vasoconstriction and attenuated pulmonary inflammation and respiratory failure. Platelet activation was not altered by transfusion of SRBCs, but ADP more readily activated these platelets. Therefore, patients with HS might benefit from breathing NO when resuscitated with SRBCs. Disclosures:Bloch:Massachusetts General Hopsital: Research Funding. Zapol:Massachusetts General Hopsital: Dr. Zapol receives royalties from patents on inhaled nitric oxide licensed by MGH to Linde (Munich, Germany) and Ikaria (Clinton, NJ)., Dr. Zapol receives royalties from patents on inhaled nitric oxide licensed by MGH to Linde (Munich, Germany) and Ikaria (Clinton, NJ). Patents & Royalties.

Should I stay or should I go?: Physiological, metabolic and biochemical consequences of voluntary emersion upon aquatic hypoxia in the scaleless fish Galaxias maculatus

Hypoxia represents a significant challenge to most fish, forcing the development of behavioural, physiological and biochemical adaptations to survive. It has been previously shown that inanga (Galaxias maculatus) display a complex behavioural repertoire to escape aquatic hypoxia, finishing with the fish voluntarily emerging from the water and aerially respiring. In the present study we evaluated the physiological, metabolic and biochemical consequences of both aquatic hypoxia and emersion in inanga. Inanga successfully tolerated up to 6h of aquatic hypoxia or emersion. Initially, this involved enhancing blood oxygen-carrying capacity, followed by the induction of anaerobic metabolism. Only minor changes were noted between emersed fish and those maintained in aquatic hypoxia, with the latter group displaying a higher mean cell haemoglobin content and a reduced haematocrit after 6h. Calculations suggest that inanga exposed to both aquatic hypoxia and air reduced oxygen uptake and also increased anaerobic contribution to meet energy demands, but the extent of these changes was small compared with hypoxia-tolerant fish species. Overall, these findings add to previous studies suggesting that inanga are relatively poorly adapted to survive aquatic hypoxia.

Postpartum haemorrhage and haematological management

Postpartum haemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide. Recent report of the Centre for Maternal and Child Enquiries (CMACE) in the United Kingdom, which was previously called Confidential Enquiries into Maternal and Child Health (CEMACH), confirmed a reduction in maternal deaths during the last Triennium (2006–2008). This is attributed to improvements in timely diagnosis and prompt and aggressive treatment. PPH is now the sixth most common direct cause of maternal deaths in the U.K. World Health Organization (WHO) estimates that postpartum haemorrhage accounts for 25% of maternal deaths worldwide. Substandard care and ‘too little being done too late’ remain a significant contributor of maternal deaths.Primary PPH refers to a blood loss from the genital tract of 500 ml or more within 24 h of delivery (or >1000 ml during caesarean section). Secondary PPH refers to an excessive blood loss between 24 h and 6 weeks after birth. Massive PPH refers to a blood loss of over 2000 ml (or >30% of blood volume) and is associated with increased maternal morbidity and mortality. A timely, multi-disciplinary and systematic approach to restore the volume, clotting system and the oxygen carrying capacity of blood, whilst steps are taken to arrest bleeding, is essential to save life.Primary postpartum haemorrhage is caused by uterine atony, genital tract trauma, retained placental tissue and membranes after birth or coagulopathy. The latter may not only be a cause of PPH, but also could be an effect of massive haemorrhage due to a ‘washout phenomenon’. Rapid and profuse bleeding results in loss of platelets and clotting factors, that get ‘washed out’. This may lead to a depletion of coagulation factors and resultant bleeding.

Fanconi anaemia with bilateral diffuse pulmonary arterio venous fistulae: a case report

BackgroundWe report a patient with cytogenetically confirmed Fanconi anaemia with associated diffuse bilateral pulmonary arterio-venous fistulae. This is only the second reported case of diffuse pulmonary arterio-venous fistulae with Fanconi anaemia.Case PresentationA 16 year old Sri Lankan boy, with a cytogenetically confirmed Fanconi anaemia was admitted to University Medical Unit, National Hospital of Sri Lanka for further assessment and treatment. Both central and peripheral cyanosis plus clubbing were noted on examination. The peripheral saturation was persistently low on room air and did not improve with supplementary Oxygen. Contrast echocardiography failed to demonstrate an intra cardiac shunt but showed early crossover of contrast, suggesting the possibility of pulmonary arterio-venous fistulae. Computed tomography pulmonary angiogram was inconclusive. Subsequent right heart catheterisation revealed bilateral diffuse arterio-venous fistulae not amenable for device closure or surgical intervention.ConclusionTo our knowledge, this is the second reported patient with diffuse pulmonary arterio-venous fistulae associated with Fanconi anaemia. We report this case to create awareness among clinicians regarding this elusive association. We recommend screening patients with Fanconi anaemia using contrast echocardiography at the time of assessment with transthoracic echocardiogram. Though universal screening may be impossible given the cost constraints, such screening should at least be performed in patients with clinical evidence of desaturation or when a therapeutic option such as haematopoietic stem cell transplantation is considered. Treatment of pulmonary arteriovenous fistulae would improve patient outcome as desaturation by shunting worsens the anaemic symptoms by reducing the oxygen carrying capacity of blood.

Reduced O2 concentration during CAM development—Its effect on physiological parameters of broiler embryos

Embryo development is a dynamic process, determined by both the genetic background of the organism and the environment in which it develops. Environmental alterations during an organism's embryogenesis may induce changes in the development of some physiological regulatory systems, thereby causing permanent phenotypic changes in the embryo. The present study aimed to assess the effect of 17% O(2) concentration during chorioallantoic membrane (CAM) development on a) CAM development, b) cardiovascular parameters, and c) embryo development postexposure and up to hatch. Two replicated trials, each with 840 fertile Cobb eggs, were conducted. At embryonic d 5 (E5) eggs were divided into 2 treatments: 1) control, and 2) 17% O(2) concentration for 12 h/d from E5 through E12 (12H). The 12H embryos exhibited a clear and significant increase in the vascular area of the CAM, which grew to 6.8% larger than that of the control. Hematocrit and hemoglobin levels, as measured on E13 and E14, increased in response to the hypoxic treatments, but these differences were not maintained subsequently. Heart rate and relative heart weight were not affected by hypoxic exposure, but eggshell temperature in the 12H treatment was higher than that of the control, indicating higher heat production, which is consistent with the elevated plasma concentrations of triiodothyronine and thyroxin and with the enhanced oxygen consumption and residual yolk intake rate that followed exposure to hypoxic conditions. These findings indicate that embryos adapted to hypoxic condition enhance angiogenesis processes, which subsequently increase their blood oxygen-carrying capacity, enabling the increase of oxygen consumption, which positively affects their growth development and maturation compared with the control embryos. Such alterations may affect posthatch performance and the ability of broilers cardiovascular system to meet elevated oxygen demand.