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PubMed1999

Packing for the journey. Character traits for transcultural care.

Eight-four pounds," the seaplane attendant announced approvingly. As two nursing students and an instructor, we were on our way to a remote First Nations village in northern Canada as part of a transcultural clinical course at a Canadian Christian university. Our groceries for three weeks were boxed up and weighed to ensure that the carrying capacity of the seaplane was not exceeded. We had packed carefully, giving priority to items that were nutritious, lightweight and compact. We hoped we had the essentials. We felt prepared.

Attitude of Health Personnel↗
PubMed1993

Activation of complement by Fluosol attributable to the pluronic detergent micelle structure.

Fluosol, a complex mixture of perfluorocarbons with a high oxygen-carrying capacity emulsified with the detergent pluronic F-68 and various lipids, recently was approved for adjuvant therapy to reduce myocardial ischemia during coronary angioplasty. Anaphylactoid reactions after Fluosol infusion through activation of the complement pathway have been reported in some patients. We examined the mechanism of complement activation by Fluosol. In vitro, incubation of both dog and human plasma with Fluosol for 1 h caused a significant reduction in total hemolytic complement levels (CH50). None of the individual components of Fluosol tested activated complement. A reduction in CH50 levels similar to that observed with Fluosol was obtained after incubation of dog or human plasma with the detergent pluronic F-68 in combination with either perfluorocarbon. In vivo, a bolus injection of the detergent and perfluorocarbon fully mimicked the anaphylactoid reaction of Fluosol previously observed in dogs, with transient profound hypotension, tachycardia, and reduction in CH50 levels occurring < or = 5 min. To investigate further the mechanism by which the pluronic/perfluorocarbon combination activates complement, an inert dense liquid (mineral oil or silicon oil) substituted for the perfluorocarbons produced comparable complement activation both in vitro and in vivo. These observations suggest that creation of a larger pluronic micelle around a core of perfluorocarbons or any inert dense substance, causes formation of a specific surface configuration, resulting in activation of the complement cascade.

Animals↗
PubMed1977

Improved retention of stroma-free hemoglobin solution by chemical modification.

The major problems requiring solution before full-scale evaluation of stroma-free hemoglobin solution (SFHS) in a clinical environment are its high oxygen affinity and relatively short intravascular retention time. Through postmanufacture chemical modification of SFHS we have been able to improve both properties as determined in in vitro and in vivo studies. Permatization of SFHS with pyridoxal 5'-phosphate (PLP) does not affect oxygen-carrying capacity and improves the P50 and intravascular retention. This chemically modified hemoglobin is worthy of further evaluation.

Animals↗
PubMed1978

Abnormal heme-protein patterns in hemorrhagic shock.

Allegedly toxic heme pigments have been described in the serum of animals bled to hemorrhagic shock (5,7). In addition, Sears et al. (9), and Braun et al. (1) have shown that the products derived from the degradation of hemoglobin following intravascular hemolysis were toxic (heme carried by hemopexin and albumin). The accumulation of metabolites, caused by the impeded circulation, degrades free hemoglobin into heme pigments and their concentration then reaches a level which exceeds the normal heme-carrying capacity of serum proteins. We have already demonstrated the presence of abnormal heme pigments in clinical cases of shock using scanning spectrophotometry (3). We have endeavored to identify these pigments by serum electrophoresis, and to relate the appearance of some of these compounds to mortality rates. There were no deaths associated with the presence of haptoglobin-hemoglobin alone in serum. As shock deepened and mortality rose, hemopexin-heme and methemalbumin appeared. The highest mortality rate (4 out of 5 cases) was found when both hemopexin-heme and methemalbumin were present. It appears, therefore, that the administration of serum proteins in shock may reduce the toxicity of the products of degradation formed in low-flow states.

Blood Proteins↗
PubMed1982

Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2 in injured patients.

Post-trauma patients have an oxygen consumption which is proportional to oxygen delivery, suggesting that tissue oxygen consumption is limited by diffusion. Transfusion of packed red blood cells (RBC), which increases the oxygen-carrying capacity of blood, would be expected to increase mixed venous PO2, thereby improving tissue oxygenation. However, the low P50 of stored blood may increase the affinity of hemoglobin for oxygen and reduce oxygen consumption. To evaluate the net effect of these mechanisms, we studied hemodynamic and oxygen transport parameters before and after RBC transfusion in eight critically ill patients. Mixed venous O2 content was measured directly by fuel cell O2 analyzer, and standard P50 was calculated. Following transfusion of one unit of packed RBC which increased mean hemoglobin from 9.2 +/- 0.3 gm/dl to 10.1 +/- 0.3 gm/dl (p less than 0.01), there were no changes in oxygen delivery (490 +/- 80 ml/min/m2), oxygen consumption (210 +/- 30 ml/min/m2), or mixed venous PO/ (37 +/- 2 Torr). Cardiac index (4.1 +/- 0.71 L/min) decreased by 0.4 L/min/m2 (p less than 0.05). Standard P50 decreased by 4.2 +/- 2.4 Torr following transfusion of two units of RBC (p less than 0.05). Red blood cell transfusion thus failed to increase oxygen consumption in these patients, despite an increase in oxygen content. Thus, RBC transfusion may not improve tissue oxygenation.

Adult↗
PubMed2001

Oxygen transport dynamics of acellular hemoglobin solutions in an isovolemic hemodilution model in swine.

BACKGROUND: One of the perceived advantages of a hemoglobin-based blood substitute is the provision of oxygen-carrying capacity. Although the hemodynamic response to the infusion of acellular hemoglobin solutions has been extensively studied, less is known about the oxygen transport dynamics of such solutions. We hypothesized that acellular hemoglobin solutions are useful oxygen carriers in anemic states and that higher P50 solutions transport O2 more efficiently than low P50 solutions. We sought to quantify O2 transport dynamics of hemoglobin solutions in an isovolemic hemodilution model in swine. METHODS: Eighteen swine were anesthetized, ventilated, and instrumented for hemodynamic measurements and for withdrawal of arterial and mixed venous blood. The swine were randomized into three groups and progressively bled from an initial hematocrit (Hct) of 30% to Hcts of 19%, 13%, and 8% using isovolemic exchange with pyridoxalated hemoglobin polyoxyethylene conjugate (PHP, n = 6); an identical hemoglobin solution without the pyridoxalation, resulting in a low P50 solution (POE-Hb, n = 6); or an osmotically similar control solution of pentastarch (PS, n = 6). Hemodynamic measurements, arterial and mixed venous O2 content, and O2 extraction ratio (ER), were determined in whole blood (WB), the red blood cell (RBC) phase, and the plasma phase utilizing a compartmentalized approach. RESULTS: Mean pulmonary arterial pressure was higher with hemodilution in the PHP and POE-Hb groups than in the PS group (p < 0.05). Cardiac index increased with hemodilution in all groups, but was significantly less than the cardiac index in the PS group at Hcts = 19% and 13%. Oxygen delivery and consumption were maintained at all hematocrits at baseline levels in the PHP and POE-Hb groups, but O2 delivery was significantly decreased in the PS group at Hct = 8% (p < 0.05 for PS vs. baseline and p < 0.05 for PHP and POE-Hb vs. PS). Oxygen extraction ratio increased with progressive hemodilution in both the RBC hemoglobin and plasma phases to a maximum of 39% for PHP and 36% for POE-Hb at Hct = 8%. The percent contribution from the plasma phase to total oxygen delivery and consumption likewise increased with hemodilution to maximum values of 52.7% (PHP) and 68.2% (POE-Hb) for delivery and 40.9% (PHP) and 39.3% (POE-Hb) for consumption. CONCLUSION: Acellular hemoglobin solutions provide a significant contribution to O2 delivery and consumption, particularly in severe anemia, in this model of isovolemic exchange. The differences in the P50 of the two hemoglobin solutions do not appear to significantly influence oxygen dynamics over the range of hematocrits studied.

Animals↗
PubMed1997

Using blood gases for the v.i.p..

UNLABELLED: We have tried to expand the routine analysis of blood gases to include some fine-tuning aspects of critical care. Test your understanding by answering the following question: A 70-year-old smoker falls into Lake Dillon (outside Denver) suffering a near-drowning episode. The pulse oximeter shows 93% on 6L nasal oxygen. His pulse and blood pressure are normal. Because you've read this article, you know that the patient's smoking habit and the city's elevation can affect the pulse oximeter's accuracy, leading one to underestimate the severity of the problem. So, you draw labs and note that his hemoglobin is 12, with blood gases showing PaO2 of 90, PaCO2 of 30 and a pH of 7.36. The lab forgot to calculate the base excess for you and his temperature is 89 degrees F rectally. A diagnosis of life-threatening inadequate oxygenation is supported by which of the following astute observations: a) An abnormal base deficit is proven by the borderline acidic pH and the low PaCO2. b) His anemia reduces both his buffer base and his oxygen carrying capacity. c) His hypothermia overstates his PO2 because the blood was heated up before measurement. d) His smoking makes a CO level likely, worsening his anemia and ignored by the pulse oximeter. e) The high level of supplemental oxygen has minimal effect on his arterial oxygen tension, showing severe pulmonary gas transfer problems (shunting). f) The measurement of his PaO2 is artificially high because he is at altitude. ANSWER: All of the following except (f). Measuring his oxygen tension at altitude actually works in his favor, since the barometric effect will be to reduce the PaO2 at a given level of sea level pathology. Now you are ready to give your patients the V.I.P. treatment!

Acid-Base Equilibrium↗
PubMedDate not supplied

Tired blood. Part 1.

"Tired blood" is a common term used to describe anemia because of the association between fatigue, often the first sign of anemia, and the idea that it has "something to do with blood." Today, millions of people have diagnosed anemia, and millions more with chronic diseases are at risk for developing anemia. Anemia is not a specific disease; rather, it is an indication that something has either disturbed the maturation of essential red blood cells or interfered with the oxygen carry capacity of red cells. In this two-part series about tired blood, the etiology and pathophysiology of selected forms of anemia are discussed and pharmacotherapy designed to address the condition of anemia is identified. Part 1 addresses anemia related to red blood cell development, and Part 2 explores the physiology of hemoglobin-related anemia and inherited anemia.

Anemia↗
PubMedDate not supplied

Progression of unsupported curves in adolescent idiopathic scoliosis.

Stability of three types of double scoliotic curves of 10-40 degrees was analyzed using a biomechanical model: double primary (Type I), primary thoracic with compensatory lumbar (Type II), and primary lumbar with compensatory thoracic (Type III). The load-carrying capacity of each curve was analyzed as a function of magnitude of the curve, its location and flexibility. Curve magnitude was found to be the most influential parameter governing the stability of a scoliotic curve up to 30 degrees. Results suggest that in evaluating curves of comparable magnitudes, Type I and II curves are more likely to progress and, therefore, should be braced at an earlier stage than Type III curves.

Adolescent↗
PubMed2001

Effects of profound anemia on brain tissue oxygen tension, carbon dioxide tension, and pH in rabbits.

This study sought to determine the maximum tolerable limit of anemia for the brain during halothane anesthesia. Using a multiparameter sensor, we continuously monitored brain tissue oxygen tension (PO2), carbon dioxide tension (PCO2), and pH during profound hemodilution and subsequent transfusion. Twelve New Zealand White rabbits were anesthetized, intubated, and mechanically ventilated at a fraction of inspired oxygen (FiO2) of 21% to produce an arterial carbon dioxide tension (PaCO2) of 35 to 40 mm Hg. The femoral artery was cannulated to continuously monitor arterial blood pressure and to intermittently measure arterial blood gases. The electroencephalogram (EEG) was recorded throughout the course of the study. A fiberoptic sensor was inserted into the brain for the continuous measurement of brain PO2, PCO2, pH, and temperature. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Severe anemia was induced by repeatedly withdrawing 50-mL aliquots of blood and infusing an equal volume of 6% hetastarch. This procedure was performed four times for each rabbit. After the forth blood draw and fluid infusion, a total of 60 mL of packed red blood cells were transfused. Upon completion of the hemodilution, the hemoglobin concentration was 2.4 +/- 0.3 g/dL (mean +/- SEM). Brain tissue PO2 decreased from 27 +/- 3 mm Hg to a minimum of 12 +/- 2 mm Hg. Brain tissue pH also decreased from 7.22 +/- 0.03 to 7.12 +/- 0.05 and returned to the baseline value with transfusion. Brain PCO2 did not change significantly during the experiment. Cerebral blood flow increased from 37 +/- 3 to 66 +/- 15 mL x 100 g(-1) x min(-1) during hemodilution and returned to baseline after infusion of red blood cells. There was some loss of EEG amplitude and the calculated cerebral metabolic rate (CMRO2) decreased from 4.3 +/- 0.6 to 1.9 +/- 0.3 mL x 100 g(-1) x min(-1) at the most profound level of anemia. This is the first report of which the authors are aware of continuous monitoring of brain tissue pH, PCO2, and PO2 during profound hemodilution and transfusion. Hemodilution results in a decrease in brain tissue PO2. Increases in CBF and oxygen extraction can only partially compensate for the decreased oxygen carrying capacity of the blood. Decreases in brain tissue PO2, pH, CMRO2, and a loss of EEG amplitude suggest that the maximum tolerable limit of hemodilution was achieved in this study.

Anemia↗
PubMed1995

Experimental therapies to improve delivery of oxygen and substrate in acute stroke.

The results of large-scale clinical trials of hemodilution therapy and vasodilators for acute stroke have been disappointing. However, interventions involving the manipulation of whole blood viscosity, blood oxygen-carrying capacity, cardiac output, and the resistance properties of cerebral vessels are viable therapeutic modalities currently being investigated. The central aim of all of these therapies is the timely improvement of perfusion and substrate delivery to ischemic brain regions. Better understanding of cerebrovascular flow regulation and the physiology of microvessels may give rise to more effective therapies. In the past, overemphasis on hematocrit reduction and cerebral vasodilators has obscured the potential risks of reducing blood oxygen content and vascular resistance during acute stroke and the importance of optimizing oxygen delivery by other means, in particular by cardiac output augmentation and manipulation of plasma properties. A broader approach to therapeutic strategies for acute stroke includes not only increasing cerebral blood flow, but also interventions that will create favorable changes in the humoral microenvironment and promote overall substrate delivery to the brain.

Acute Disease↗
PubMed1996

Intraoperative and postoperative blood salvage.

Surgical patients present unique opportunities for reducing allogeneic transfusions via perioperative blood salvage. Intraoperative cell saver techniques enable the collection of autologous blood from the surgical field and cardiopulmonary bypass circuit for return to the patient. Washing and hemoconcentration creates a product with an average hematocrit of 50% that carries normal erythrocyte survival, with minimal coagulation factors of platelets. Postoperative autotransfusion of shed blood from chest tubes or surgical drains enables additional blood conservation, reducing allogeneic transfusions by as much as 50%. Both intermittent and continuous autotransfusion systems using standard chest drainage equipment are available that require minimal setup and maintenance at the bedside. The hematocrit of shed blood is 20-25%, with depletion of clotting factors and platelet function. Potential advantages of perioperative blood salvage include the ready availability of large volumes of patient-compatible blood, with optimal oxygen-carrying capacity, that is virtually free from the risk of viral contamination. Specific indications, contraindications, and techniques for the salvage and administration of these vital products are presented.

Blood Transfusion, Autologous↗
PubMed1996

Alternative oxygen carriers.

Alternative oxygen carriers are being evaluated in human studies. Information from the clinical evaluation of these "blood substitutes" is not publicly available. Preclinical studies of solutions of modified cell-free hemoglobin and of perfluorocarbon emulsions have demonstrated significant toxicity. Hemoglobin inactivates endothelium-derived nitric oxide, participates in free-radical reactions, is a neurotoxin, activates the immune system, potentiates the effects of bacterial endotoxin, and increases the lethality of certain bacterial infections. Perfluorocarbon emulsions activate complement and cause lung dysfunction. Both materials have short intravascular half-lives. Safe doses of perfluorocarbon emulsions have very limited oxygen-carrying capacity. Protein engineering to reduce the toxicities of the modified hemoglobins is ongoing. A safe and effective erythrocyte substitute is still a distant goal.

Blood Substitutes↗
PubMed2004

Carboxyhemoglobin formation as an unexpected side effect of inhaled nitric oxide therapy in severe acute respiratory distress syndrome.

OBJECTIVE: To report an unexpected cause of carboxyhemoglobinemia associated with inhaled nitric oxide therapy in severe acute respiratory distress syndrome. DESIGN: Case report. SETTING: Medical critical care unit at Lausanne University Hospital. PATIENT: One female patient with acute respiratory distress syndrome treated with inhaled nitric oxide, who developed a simultaneous increase in blood methemoglobin and carboxyhemoglobin. CONCLUSIONS: Potential pathophysiologic mechanisms linking acute respiratory distress syndrome, inhaled nitric oxide, methemoglobin, and carboxyhemoglobin are discussed. Since carboxyhemoglobin has a negative influence on oxygen-carrying capacity, this effect may potentially offset the beneficial influence (if any) of inhaled nitric oxide on arterial PO2. This observation does not support the use of inhaled nitric oxide in the treatment of acute respiratory distress syndrome.

Administration, Inhalation↗
PubMed2005

Faster development does not lead to correlated evolution of greater pre-adult competitive ability in Drosophila melanogaster.

In comparisons across Drosophila species, faster pre-adult development is phenotypically correlated with increased pre-adult competitive ability, suggesting that these two traits may also be evolutionary correlates of one another. However, correlations between traits within- and among- species can differ, and in most cases it is the within-species genetic correlations that are likely to act as constraints on adaptive evolution. Moreover, laboratory studies on Drosophila melanogaster have shown that the suite of traits that evolves in populations subjected to selection for faster development is the opposite of the traits that evolve in populations selected for increased pre-adult competitive ability. This observation led us to propose that, despite having a higher carrying capacity and a reduced minimum food requirement for completing development than controls, D. melanogaster populations subjected to selection for faster development should have lower competitive ability than controls owing to their reduced larval feeding rates and urea tolerance. Here, we describe results from pre-adult competition experiments that clearly show that the faster developing populations are substantially poorer competitors than controls when reared at high density in competition with a marked mutant strain. We briefly discuss these results in the context of different formulations of density-dependent selection theory.

Adaptation, Physiological↗
PubMed1983

Physiological variation of mouse haemoglobins.

Polymorphism at Hbb (haemoglobin beta-chain) is widespread in natural populations of the house mouse, Mus musculus, and appears to be maintained by natural selection. This report is an attempt to correlate genotypic fluctuations at Hbb with a most important physiological attribute of haemoglobin, its oxygen carrying capacity. Oxygen affinity has been studied and P50 values have been measured in 12 inbred strains as well as wild-caught mice from Skokholm island. The mean P50 of each inbred strain is a constant characteristic, although there is high within-strain variation and the oxygen affinity of the blood of an individual can fluctuate considerably from week to week. The causes of this variation remain obscure but neither within-strain nor between-strain differences are correlated with known modulators of oxygen binding. In general, the blood of mice of inbred strains as well as wild-caught mice that are homozygous for Hbbd tends to have a higher oxygen affinity than that from comparable animals homozygous for Hbbs, but it seems likely that the oxygen dissociation properties of haemoglobin are not the only ones important in determining differential survival of a particular Hbb type under varying environmental stress.

Animals↗
PubMed1997

Dynamics of two feline retroviruses (FIV and FeLV) within one population of cats.

We present a deterministic model of the dynamics of two microparasites simultaneously infecting a single host population. Both microparasites are feline retroviruses, namely Feline Immunodeficiency Virus (FIV) and Feline Leukaemia Virus (FeLV). The host is the domestic cat Felis catus. The model has been tested with data generated by a long-term study of several natural cat populations. Stability analysis and simulations show that, once introduced in a population, FIV spreads and is maintained, while FeLV can either disappear or persist. Moreover, introduction of both viruses into the population induces an equilibrium state for individuals of each different pathological class. The viruses never induce the extinction of the population. Furthermore, whatever the outcome for the host population (persistence of FIV only, or of both viruses), the global population size at the equilibrium state is only slightly lower than it would have been in the absence of the infections (i.e. at the carrying capacity), indicating a low impact of the viruses on the population. Finally, the impact of the diseases examined simultaneously is higher than the sum of the impact of the two diseases examined separately. This seems to be due to a higher mortality rate when both viruses infect a single individual.

Animals↗
PubMed2001

The quality and isolation of habitat patches both determine where butterflies persist in fragmented landscapes.

Habitat quality and metapopulation effects are the main hypotheses that currently explain the disproportionate decline of insects in cultivated Holarctic landscapes. The former assumes a degradation in habitat quality for insects within surviving ecosystems, the latter that too few, small or isolated islands of ecosystem remain in landscapes for populations to persist. These hypotheses are often treated as alternatives, and this can lead to serious conflict in the interpretations of conservationists. We present the first empirical demonstration that habitat quality and site isolation are both important determinants of where populations persist in modern landscapes. We described the precise habitat requirements of Melitaea cinxia, Polyommatus bellargus and Thymelicus acteon, and quantified the variation in carrying capacity within each butterfly's niche. We then made detailed surveys to compare the distribution and density of every population of each species with the size, distance apart and quality of their specific habitats in all their potential habitat patches in three UK landscapes. In each case, within-site variation in habitat quality explained which patches supported a species' population two to three times better than site isolation. Site area and occupancy were not correlated in any species. Instead of representing alternative paradigms, habitat quality and spatial effects operate at different hierarchical levels within the same process: habitat quality is the missing third parameter in metapopulation dynamics, contributing more to species persistence, on the basis of these results, than site area or isolation. A reorientation in conservation priorities is recommended.

Animals↗