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PubMed1992

Ultra-pure polymerized bovine hemoglobin blood substitute: effects on the coronary circulation.

The effects of stroma-free hemoglobin (SFHgb) on the coronary circulation remain unclear. An intact canine model utilizing intracoronary adenosine to abolish the confounding effect of autoregulation was used to study maximal myocardial oxygen delivery during progressive hemodilution with polymerized bovine SFHgb. The circumflex coronary artery was instrumented with a flow probe, hydraulic constrictor, and proximal and distal catheters for adenosine infusion and distal pressure measurement, respectively. This preparation was used to generate diastolic coronary pressure-flow relations during maximal vasodilation. Maximal coronary conductance and maximal myocardial oxygen delivery were determined in two groups of 7 dogs each following hemodilution, first with 6% hetastarch (Control), followed by further hemodilution with ultra-pure, polymerized, bovine SFHgb. After hemodilution with SFHgb, maximal coronary flow increased slightly without evidence of coronary vasoconstriction. Since hemodilution with this material increases oxygen carrying capacity, maximal oxygen delivery is greater than Control, despite the very low canine hematocrit. These findings suggest: 1) SFHgb can provide adequate oxygen delivery to the myocardium despite extreme degrees of hemodilution, and 2) in this intact model, there is no evidence of adverse coronary vasomotion.

Animals↗
PubMed1994

Inclusion of ganglioside GM1 into liposome encapsulated hemoglobin does not extend circulation persistence at clinically relevant doses.

This investigation has evaluated the substitution of ganglioside GM1 for dimyristoyl phosphatidylglycerol (DMPG) in the preparation of liposome encapsulated hemoglobin (LEH), with the intention of increasing the circulation persistence of this potential oxygen carrier. Although equivalent yields of each formulation were produced by microfluidization, the hemoglobin encapsulation efficiency was greater for GM1-LEH than DMPG-LEH. Similar particle sizes, phospholipid content, methemoglobin levels, and oxygen-carrying capacity were observed for both formulations. Zeta potential measurements to monitor liposomal surface charge showed GM1-LEH to be more electropositive than DMPG-LEH. Using differential scanning calorimetry, similar enthalpy values and hemoglobin structural transition temperatures were determined for both LEH formulations. Circulation persistence of each LEH formulation was determined following a 0.25 ml (1 g phospholipid/Kg body weight) or 0.5 ml (2 g phospholipid/Kg body weight) injection in mice. During the first 18 hours, GM1-LEH was cleared at a faster rate than DMPG-LEH at both dosages studied. Then the remaining liposomes of each formulation were removed with identical circulation profiles until no liposomes were remaining in circulation at either 50 hours (0.25 ml) or 72 hours (0.5 ml) post-injection. These data reveal that the use of ganglioside GM1 to solely increase the circulation persistence of LEH was of little benefit.

Animals↗
PubMed1994

Production of PEG-modified bovine hemoglobin: economics and feasibility.

Bovine hemoglobin has many advantages as a blood substitute: a) it's ready availability; b) it's low cost; c) it's oxygen carrying capacity; and d) the ease with which it can be modified with polyethylene glycol (PEG) to improve its pharmacokinetic profile. This study investigates the potential of PEG-modified bovine hemoglobin as a cost-effective blood substitute.

Animals↗
PubMed1995

Review of modified hemoglobin research at Letterman: attempts to delineate the toxicity of cell-free tetrameric hemoglobin.

In the final two years, June 1991 to June 1993, of the Letterman Army Institute of Research, a variety of cell, tissue, organ, and animal systems were used to explore the toxicities of model hemoglobin (Hb) solutions produced in the sterile Hb production facility. Human mononuclear cells release TNF alpha and Il-8 when exposed to chromatographically purified human Hb (HbA0). Mixed cultures of fetal mouse neurons and glial cells exhibit neuronal death with exposure to HbA0 in a dose and time dependent manner while the glial cells are not injured. Isolated perfused rabbit hearts were used to explore the reversibility of coronary vasoconstriction after Hb and cyanomet-Hb administration, and deferoxamine was shown to partially protect that reversibility. In rabbits HbA0 and human Hb cross-linked with bis(3,5-dibromosalicyl) fumarate (alpha alpha Hb) caused hypertension and pulmonary arteritis. In swine, HbA0 and alpha alpha Hb caused systemic and pulmonary hypertension and a doubling of the vascular resistance that was equivalent to that seen with inhibition of nitric oxide synthesis. Elevations of creatine kinase and lactic dehydrogenase activity were observed after Hbs were infused, but not after blockade of nitric oxide synthesis. Acute renal failure seen after administration HbA0, did not appear after alpha alpha Hb. Infusion of cyanomet-alpha alpha Hb did not cause the increased vascular resistance seen after alpha alpha Hb. The infusion of 1-arginine or nitroglycerine with alpha alpha Hb did not prevent the increased vascular resistance and decreased cardiac output or allow the increased oxygen carrying capacity provided by Hb in the plasma from translating into improved oxygen delivery or improved oxygen consumption.

Animals↗
PubMed1996

Alteration of cerebral microcirculation by hemodilution with hemosome in awake rats.

Our study showed that hemodilution with modified fluid gelatin resulted in an increase in local cerebral blood flow (LCBF), but no change at all in local cerebral oxygen delivery (LCOD) in rats. Hemosome, a lecithin encapsulated hemoglobin having the oxygen-carrying capacity, was developed to improve LCOD by hemodilution. Therefore, we have hypothesized that LCBF & LCOD would be increased by hemodilution with hemosome. To test this hypothesis, adult male Sprague-Dawley rats weighing approximately 350g were used and divided into the hemodilution and the control groups. Hemosome was made from pig red blood cells and lecithin. It's mean diameter was approximately 0.3 um and hemoglobin concentration was approximately 4g/dl. Isovolemic hemodilution, which lowered the systemic hematocrit from approximately 50% to approximately 30%, was achieved by rapidly replacing blood with the same volume of hemosome. Ten min later, LCBF in 14 brain structures were measured using the 14C-iodoantipyrine technique. Our results showed that LCBF of the control group ranged from 115 +/- 11 ml/100g/min in the medulla to 260 +/- 31 ml/100g/min in the occipital cortex. LCBFs were generally higher (p < 0.05, MANOVA) by 16% in the hemodilution group than in the control group. However LCODs were generally decreased (p < 0.05, MANOVA) by 18% in the hemodilution group than in the control. In conclusion, hemodilution with hemosome indeed improves LCBF but lowers LCOD in awake rats.

Analysis of Variance↗
PubMed1997

Effect of diaspirin crosslinked hemoglobin on systemic and regional blood circulation in pregnant rats.

Diaspirin crosslinked hemoglobin (DCLHb: Baxter Healthcare Corp., Round Lake, IL, USA) is a biochemically stable hemoglobin based solution with excellent oxygen carrying capacity. Studies have been conducted in male rats to determine the effect of DCLHb on systemic and regional blood circulation. However, the cardiovascular effect of DCLHb has not been studied in female rats. In the present study the effect of DCLHb (400 mg/kg, i.v.) was observed on systemic hemodynamic parameters and regional blood circulation in non-pregnant rats, and in 9-day pregnant and 18-day pregnant rats. DCLHb increased mean arterial pressure (MAP) and total peripheral resistance (TPR) and increased blood flow to the heart, gastrointestinal tract (GIT), mesentery & pancreas, and skin in all groups of rats. The basal blood flow to the ovaries was higher in 18-day pregnant rats when compared to non-pregnant and 9-day pregnant rats. DCLHb further increased blood flow to the ovaries of 18-day pregnant rats. It is concluded that DCLHb increases blood flow to the heart, GIT and skin as a result of redistribution of blood from the musculoskeletal system. Blood flow in female reproductive organs is not altered by DCLHb in non-pregnant rats and during mid-term pregnancy. However, in advanced stages of pregnancy DCLHb increases blood flow to the ovaries.

Animals↗
PubMedDate not supplied

Stroma-free methemoglobin solution as an antidote for cyanide poisoning: a preliminary study.

Effective treatment of cyanide poisoning requires rapid diagnosis, good supportive treatment and the use of a specific antidote. The currently available antidotes offer demonstrated efficacy along with significant potential adverse side effects. We have investigated an alternate approach to antidote therapy for cyanide poisoning by using Stroma-Free Methemoglobin Solution ( SFMS ). Rats injected with an LD100 intravenous dose of cyanide were treated with SFMS equal to 1.5% of their total body hemoglobin. There was a highly significant increase in the survival rate of the treated group compared to saline controls. The potential advantages of SFMS over current antidotes include an immediate onset of action, rapid elimination of cyanide from the body and a mode of action that doesn't compromise any of the patients' oxygen carrying capacity. SFMS shows promise as a significant adjunct in the treatment of cyanide poisoning.

Animals↗
PubMed1992

A model of the transmission of dengue fever with an evaluation of the impact of ultra-low volume (ULV) insecticide applications on dengue epidemics.

We have developed a deterministic susceptible, exposed, infectious, resistant or removed (SEIR) model of dengue fever transmission that enables us to explore the behavior of an epidemic, and to experiment with vector control practices. Populations of both host and vector are divided into compartments representing disease status (susceptible, exposed, infectious, and, for humans, resistant), and the flow between compartments is described by differential equations. Examination of the equilibrium points leads to a formulation of the basic reproduction rate (Z0) of the disease. With a base set of parameters, Z0 = 1.9 and the model realistically reproduces epidemic transmission in an immunologically naive population. Control of adult mosquitoes by ultra-low volume (ULV) aerosols is simulated by an abrupt decrease in vector densities, followed by gradual recovery of the vector population. The model indicates that ULV has little impact on disease incidence, even when multiple applications are made, although the peak of the epidemic may be delayed. Decreasing the carrying capacity of the environment for mosquitoes, and thus the basic reproduction rate of the disease, by source reduction or other means, is more effective in reducing transmission.

Animals↗
PubMed1975

Lactic acidosis from carboxyhemoglobinemia after smoke inhalation.

Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia.

Acidosis↗
PubMed1970

Anthrax epizootic in white-tailed deer.

Bacillus anthracis caused high mortality among white-tailed deer (Odocoileus virginianus) on Beulah Island, Desha County, Arkansas. Sixty-seven carcasses were located and the total loss was estimated between 200 and 300 deer. Range conditions indicated that the deer herd had greatly exceeded carrying capacity. Lesions in deer were similar to those ascribed to anthrax in domestic cattle, sheep, and goats.

Animals↗
PubMed1998

Validation of a model describing two-dimensional heat transfer during solid-state fermentation in packed bed bioreactors.

A two-dimensional heat transfer model was validated against two experimental studies from the literature which describe the growth of Aspergillus niger during solid-state fermentation in packed bed bioreactors. With the same set of model parameters, the two-dimensional model was able to describe both radial temperature gradients, which dominated in one of the studies, and axial temperature gradients, which dominated in the other study. The sensitivity of the model predictions to the characteristics of the substrate and the microbe were explored. The temperatures reached in the column are most sensitive to parameters which affect the peak heat load, including the substrate packing density, the maximum specific growth rate, and the maximum biomass concentration. Even though the bed is assumed to be aerated with saturated air, the increase in temperature with bed height increases the water-carrying capacity of the air and therefore enables evaporation to contribute significantly to cooling. The model suggests that evaporation can remove as much as 78% of the heat from the bed during times of peak heat generation. Our model provides a tool which can guide the design and operation of packed bed bioreactors. However, further improvements are necessary to do this effectively, the most important of which is the incorporation of a water balance.

Aspergillus niger↗
PubMed1999

[Genetic differences in plastic responses to density between ecotypes of Arabidopsis thaliana].

One of the most promising directions in the study of phenotypic plasticity is its detailed analysis in organisms that are also well-studied in other aspects. Also, conclusions based on plasticity studies in environmental gradients that closely mimic natural variation are shown to be the most relevant. Following those directions, we conducted this study of phenotypic plasticity on the currently best available model system in flowering plants--Arabidopsis thaliana, and utilized one of the most common variations experienced in the wild--variation in density. Four Arabidopsis thaliana commonly used inbred lines (ecotypes) were grown in densities from one to seven plants per pot. Both phenotypic plasticity and its genetic variability were detected for almost all of 11 analyzed traits, with analyzed ecotypes responding strongly to density of just two plants per pot. Density had small effect on life history and moderate effect on size traits, while vegetative and reproductive traits responded strongly. Mortality of plants during the experiment was almost absent, showing that all densities corresponded to the medium density phase in which "carrying capacity" is not yet reached. Genetic variability for phenotypic plasticity was in most cases the result of profound deviation of only one ecotype from the response of others. In the case of reproductive output, however, G x E interaction was the result of greater between-ecotype variability at lower densities. If we reasonably assume that dense stands are more common in the wild, this difference between ecotypes (populations) closely resembles the cases of so-called potential variability within populations.

Arabidopsis↗
PubMed1976

Fluid therapy in the critically injured patient.

Sufficient clotting factors to ensure coagulation and replacement of lost volume and oxygen-carrying capacity are necessary to obviate many of the complications that may occur when massive transfusions are used in patients with multiple injuries. A regimen that has been successful includes immediate infusion of plasma protein fraction, packed red cells, fresh-frozen plasma, and nonspecific platelets.

Blood Coagulation Disorders↗
PubMed2000

Management of carbon monoxide poisoning using oxygen therapy.

The management of carbon monoxide poisoning requires an accurate assessment of the extent of blood oxygenation. Measuring the fractional oxyhaemoglobin content by using co-oximetry gives a true picture of the oxygen-carrying capacity of blood in the presence of carboxyhaemoglobin. The use of readings from pulse oximetry or a standard blood gas analyser is insufficient and can be misleading. We report on a case of carbon monoxide poisoning to illustrate this potential pitfall.

Adult↗
PubMed2000

Description of a new computer wire coding method and its application to evaluate potential control selection bias in the Savitz et al. childhood cancer study.

We developed a new computer wire coding method and then applied it to investigate the suggestion that control selection bias might explain the observed association between wire codes and childhood cancer made in the study conducted by Savitz et al. in the Denver area. The computer wire coding method used a geographic information system approach with data on the local distribution electric system and from tax assessor records. Individual residences were represented as a circle scaled to the ground floor area of the residence and centered on the lot centroid. The wire code of the residence was determined from the distance between the circle and the relevant power line, and from the current carrying capacity of that line. Using this method, wire codes were generated for 238 290 residences built before 1986, the time of the Savitz et al. study, in the Denver metropolitan area. We then attempted to reconstruct the 1985 population of hypothetically eligible control children in the Denver metropolitan area by using 1980 census data. Since data were not available to locate the children in each residence within a census block, uniform, Poisson, and negative binomial distributions were used to randomly assign children to residences. To evaluate the likelihood of the wire code distribution of the controls selected by Savitz et al., 100 random trials were conducted for each distribution, matching two controls to each case. The odds ratios between childhood cancer and very high current configuration (VHCC) wire codes were reduced when the assigned controls were used, suggesting control selection bias may have been present. However, control selection bias is unlikely to account for all the reported association between childhood cancer and wire codes in the Savitz et al. study.

Bias↗
PubMed2000

Evaluation of a "heads-up" display for cardiopulmonary bypass.

Multiple variables must be analyzed during cardiopulmonary bypass in order to judge the adequacy of perfusion. Variables when viewed singly can be confusing and lead to inaccurate representation of the physiological status of the patient. Communication between the perfusionist and members of the surgical team requires accuracy and complete presentation of pertinent data. Toward this goal of improving the assimilation and processing of information during cardiopulmonary bypass, a multivariable computer-aided "Heads-up Display" (HUD) was developed. Modern jet pilots use heads-up display for rapid assimilation of information when making judgments about the performance of their aircraft and weapons systems. Heads-up display is an electronically generated display that is superimposed upon a pilot's forward field of view. An analogy between a jet pilot and a perfusionist can be made. A geometric form, a hexagon, is used as part of the heads-up display for cardiopulmonary bypass (CPB-HUD). The polygon represents a performance evaluation graph. Each of the six "spokes of a wheel" represents a physiological parameter. The represented variables are: cardiac index, peripheral vascular resistance, hematocrit, dynamic operating blood level, venous saturation, and mean arterial pressure. The perfusionist inputs target values. Target values are then compared to actual values and expressed as a percentage. If all targeted values are achieved, the graphical representation is a hexagon. The surgical team rapidly recognizes abnormal patterns that are outside individual target values. They include, but are not limited to, patterns of: vasoconstriction, vasodilatation, hypovolemia, decreased oxygen carrying capacity, and several others. The CPB-HUD has proved to be of value for planning, real time evaluation, retrospective analysis of cardiopulmonary bypass benchmark data, and as an aid in the teaching of new personnel concerned with cardiopulmonary bypass.

Cardiopulmonary Bypass↗
PubMed2000

Redox concerns in the use of acellular hemoglobin-based therapeutic oxygen carriers: the role of plasma components.

Within the past decade, most research efforts in the red blood cell substitute area have revolved about the development of acellular hemoglobin-based oxygen carriers (HBOC) as clinical replacements and/or augmentation of human blood's carrying and delivery function. A major requirement for all HBOC is the maintenance of the heme-Fe+2 in this reduced state for normal physiological behavior. Oxidation of hemoglobin results in the formation of methemoglobin (heme-Fe+3). MetHb is unable to bind oxygen thus effectively lowering the carrying capacity of the Hb-based substitute. In addition, met Hb gives rise to free radicals that have the potential to cause endothelial and surrounding tissue damage. Results of this study suggest that the normal endogenous reducing agents of human plasma have the capacity to provide redox protection and stability to specific acellular-types of HBOC. The effectiveness of these reducing agents may be related to the formal reduction potential of the HBOC being considered. The choice of buffer for HBOC storage is critical and specific to the HBOC product.

Adult↗