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PubMed1985

Cardiovascular response to exercise and training in the horse.

The quality of the overall response to exercise in the horse is very similar to that seen in man and laboratory animals; differences are mainly quantitative and persist when relative body weight is taken into account. The apparently greater flow capacity of the equine muscle bed during maximal whole-body exercise implicates the extent of central circulatory adaptations as the limiting factor in performance but implies a role for increase in arteriolar capacitance/muscle capillarity as an appropriate response to intense endurance training. The blood oxygen-carrying capacity of the horse is often quoted as the major component of the animal's superior aerobic work capacity, although the measured maximal a-vO2 for the horse is only 2 to 3 ml greater than that found in elite athletes. In fact, comparison of published performance data for man and the horse reveals that improved a-vO2 accounts for 23 per cent of the difference, and increased Qc accounts for the remaining 77 per cent of the superior oxygen consumption in the horse. The extent to which the horse can increase Qc and muscle blood flow appears to represent its major adaptations for maximal aerobic performance. It is frequently observed that there have been far greater improvements in human athletic performance than in that of the race-horse, and this difference is usually attributed to the application of scientific training methods to the athlete. It has also been suggested that the horse may have reached the limit of its adaptive ability. The horse has a maximal oxygen pulse of at least 0.6 ml per kg per beat compared with 0.35 for man, a 90 per cent whole body oxygen extraction, and an 80 to 90 per cent higher muscle blood flow, with an overall capability of increasing Vo2 max by 35 times. These represent levels that would appear to be difficult to improve upon. However, insufficient research has been performed to firmly state true maxima for the horse, and current research does not reveal to what extent the horse is capable of responding to even conventional training methods. The relative improvement that such research could reveal would provide some objective guidance to the extent to which further improvement could be anticipated. A consistent finding in the majority of studies reviewed is the tendency for results to show a lack of statistical significance, which is particularly frustrating for a researcher when the trends are consistent with the initial hypotheses. This tendency arises because of small group sizes and inherent variability in the test population.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1997

Enhancement of brain p0(2) during cardiopulmonary bypass using a hyperosmolar oxygen carrying solution.

During the past decade a new syndrome has been recognized: cerebral hypoxia secondary to cardiopulmonary bypass, resulting in impairment of cognitive memory. The incidence of the syndrome appears to be no less that 30% in patients over 65 years of age undergoing cardiac surgery. There are several factors contributing to hypoxia produced by cardiopulmonary bypass. One of these factors is crystalloid pump prime and replacement solutions devoid of (1) oxygen carrying capacity and (2) devoid of protein and its colloid osmotic pressure. This shortcoming of cardiopulmonary crystalloid solutions is partially responsible for two of the three major pathologic effects of cardiopulmonary bypass: (1) hypoxia (2) interstitial fluid accumulation (anasarca, water-logging, edema). This report describes an oxygen carrying hyperosmolar solution which enhances brain p0(2) and diminishes interstitial fluid accumulation. This blood substitute consists of perfluorcarbons and saccharides, but could consist of a hemoglobin variant plus hyperosmolar ingredients other than saccharides. The advantage of a perfluorochemical is its ability to access small channels and to be centrifuged off the patient post-operatively with a cell saver. The advantage of saccharides is that they can be metabolized by the patient for energy, and they produce a moderate diuresis coming off bypass.

Animals↗

PubMed2004

Information capacity of the corticospinal tract recordings as a neural interface.

Recording the motor output of the central nervous system from the cervical spinal cord was investigated as a method of generating voluntary command signals, potentially to be used in quadriplegic individuals. Corticospinal volleys evoked by motor cortex stimulation were recorded from the spinal cord surface with multicontact electrodes in anesthetized cats. The multicontact recordings were analyzed for their information-carrying capacity as a neural interface. Neural signals resulting from the stimulation of various points in the motor cortex were considered as symbols of an alphabet that were sent through a discrete information channel. The information capacity of this channel at the thermal noise level of the electrode contacts was calculated. The maximum information rate was 1.57 bits in a trial for a 4-symbol alphabet. The background noise that reduces the information rate to 50% of its maximum theoretical value was defined as the half-bitrate-noise-tolerance (HBR-NoiseTol) and used as a measure of symbol distinguishability. The HBR-NoiseTol for all trials on average was 24 +/- 12%, 18 +/- 10%, and 15 +/- 9% for interfaces with 2-, 3-, and 4-symbol alphabets (n = 11 trials). The average peak-to-peak amplitude of the neural volleys was 13.5 +/- 6.7 microV (n = 11). These results suggest that the corticospinal signals can be recorded with spatial selectivity from the spinal cord surface and thus warrant further investigation of their potential use for a spinal cord-computer interface.

Action Potentials↗

PubMed2005

Intelligent polymers as nonviral vectors.

The successful gene therapy largely depends on the vector type that allows a selective and efficient gene delivery to target cells with minimal toxicity. Nonviral vectors are much safer and cheaper, can be produced easily in large quantities, and have higher genetic material carrying capacity. However, they are generally less efficient in delivering DNA and initiating gene expression as compared to viral vectors, particularly when used in vivo. As nonviral vectors, polycations may work well for efficient cell uptake and endosomal escape, because they do form compact and smaller complexes with plasmid DNA and carry amine groups, which give positive charge and buffering ability that allows safe escape from endosome/lysosome. However, this is a disadvantage in the following step, which is releasing the plasmid DNA within the cytosol. In order to initiate transcription and enhance gene expression, the polymer/plasmid complex should dissociate after releasing from endosome safely and effectively. There are also other limitations with some of the polycationic carriers, for example, aggregation, toxicity, etc. Intelligent polymers, also called as 'stimuli responsive polymers', have a great potential as nonviral vectors to obtain site-, timing-, and duration period-specific gene expression, which is already exhibited in recent studies that are briefly summarized here.

Biotechnology↗

PubMed2005

A QSAR-modeling perspective on cationic transfection lipids. 1. Predicting efficiency and understanding mechanisms.

BACKGROUND: As gene therapy using viral vectors involves clinical risks, limited DNA-carrying capacity, and manufacturing problems, non-viral vectors, including cationic lipids, have been investigated. Unfortunately, these agents have significantly lower transfectional ability and, due to the complexity of the transfectional pathway, no general schemes exist for correlating cationic lipid chemistry with transfectional efficacy. METHODS: Quantitative structure-activity relationship (QSAR) analyses were carried out on sets of routinely used, experimental, and unsuccessful cationic lipid vectors taken from the literature. This approach described the amphipathic character, basicity, headgroup size, lipophilicity and shape of cationic lipids using numerical parameters. Compounds were plotted onto various parameter diagrams, and correlations were sought between numerical parameters and transfectional efficiency. RESULTS: Transfectionally effective cationic lipids fell into restricted zones in various parameter spaces, indicating that amphipathic character, lipid shape and lipophilicity were generally significant factors, whilst basicity and headgroup size were only important for certain compounds. The data supported the general significance of membrane mixing followed by induction of membrane curvature, and the more limited role of osmotic shock, as mechanisms of membrane disruption. QSAR descriptions of effective lipids permitted detailed chemical guidelines for optimizing cationic lipid structure to be given. Limitations of the approach and models are discussed. CONCLUSIONS: QSAR modeling indicated that induction of membrane curvature and osmotic shock are important mechanisms for membrane disruption by cationic lipids. The models also allowed specification of chemically detailed guidelines for selection or design of optimal cationic lipids.

Cations↗

PubMed2005

[Generation mechanism of woodland runoff and sediment on Loess Plateau under hypo-rainfall--a case study of artificial P. tabulaeformis and secondary natural P. dadidiana stands].

Based on the long-term observation and from the viewpoints of water balance and runoff-and sediment generation, this paper studied the generation processes of runoff and sediment on two typical woodlands, artificial P. tabulaeformis and secondary natural P. dadidiana, and uncultivated slope-land in Loess Plateau under hypo-rainfall. The results showed that within the range of 5.0 - 50.0 mm rainfall, the total interception of canopy and litter was 15.45 % - 56.80 % for P. tabulaeformis and 20.56% - 47.81% for P. dadidiana, and decreased with increasing rainfall. Woodlands had a higher soil water infiltration capacity than uncultivated slope-land, especially in 0-20 cm soil layer. Both the two woodlands did not generate runoff under regular rainfall. Under the assumed rainfall of 2.5 mm x min(-1) intensity and 30 min duration, P. dadidiana stand did not produce runoff, but the runoff velocity and sediment-carrying capacity of uncultivated slope-land were 23.5 times, and runoff shearing stress and energy were 8 times as much as P. tabulaeformis stand. The runoff-and sediment generation on P. tabulaeformis stand decreased by 87.6% and 99.4%, respectively, compared with those on uncultivated slopeland, which was well accorded with the average observed value in runoff plots during 1988 - 2000. The theoretical analysis on the generation mechanism of woodland runoff and sediment may be effective to evaluate the benefits of forest in soil and water conservation.

Geologic Sediments↗

PubMed1965

Displacement of one drug by another from carrier or receptor sites.

The medium of drug transfer is the water of plasma and extracellular fluid. Without complicating factors, the level of drug at a receptor site would be equal to that in the tissues and in plasma, and in dynamic equilibrium. Actually, almost all drugs are reversibly bound to proteins in plasma or tissue. The bound drug, often a high proportion of the total, acts as a reservoir, preventing wild fluctuations between ineffective and toxic levels of the biologically active unbound fraction.Displacement from a receptor site diminishes drug activity, but displacement from plasma or tissue proteins augments the effect by making more unbound drug available at the receptor site.Atropine has no intrinsic activity, but displaces acetylcholine or pilocarpine from receptors at para-sympathetic nerve endings. Similarly guanethidine competes with noradrenaline at sympathetic nerve endings, but in turn is displaced by amphetamine-like drugs.Many acidic drugs (phenylbutazone, sulfonamides, coumarin anticoagulants, salicylates, &c.) are highly bound to one or two sites on albumin molecules. When the limited carrying capacity of the plasma proteins is filled, any unbound surplus is usually soon metabolized or excreted, so the plasma level becomes restabilized. Meanwhile, however, there may be dramatic effects such as hypoglycemia, when sulfonamides are given to patients on tolbutamide, or bleeding when phenylbutazone is given to patients on warfarin.Although hormones, like thyroxine, insulin and cortisol, are carried by specific proteins, they too can be displaced. All the antirheumatic drugs so far examined have displaced cortisol and presumably driven it into tissues. This may be one mechanism of action. Possibly the sulfonylurea drugs act by displacing insulin from proteins in the pancreas, plasma or elsewhere.

Humans↗

PubMed2006

A method for purification and viral inactivation of human placenta hemoglobin.

For pilot-scale manufacturing of hemoglobin-based oxygen carrying drugs, we should get highly pure and viral inactivated hemoglobin (Hb) at high recovery. In our method, placenta hemoglobin (PHb) solutions were purified by heating in the presence of reducing agent and deoxygenating conditions so that heat-sensitive proteins were selectively precipitated and virus was inactivated. The optimum preparative condition resulted in highly purified PHb solution (>99% pure) with approximate 90% recovery and less than 2% of MetHb content, maintained oxygen carrying capacity, residual phospholipids less than 1 ppm, free of endotoxin, bacteria, type A&B antigens and virus. Finally, we compared the efficacy of blood exchange on rat with poly-PHb and poly-Hb from adult blood. The results showed no significant difference between two products. Therefore, the placenta Hb obtained from this method could be supplied as materials for oxygen carrying drugs.

Animals↗

PubMed1985

Effect of iron deficiency on energy conservation in rat liver and skeletal muscle submitochondrial particles.

Submitochondrial particles prepared from liver and skeletal muscle of control and iron-deficient rats were examined for cytochrome content and for both energy-independent and energy-conserving functions. Liver submitochondrial particles appear quite resistant to iron deficiency with cytochrome content and electron-transferring or energy-conserving functions maintained at a level of 85% or better of normal. Iron-deficient skeletal muscle submitochondrial particles, in contrast, have decreased cytochrome content and only 15-20% of the normal capacity for oxidation through either complex I (NADH dehydrogenase) or complex II (succinate dehydrogenase). Energy-linked reactions which involve substrate oxidation/reduction (succinate----NAD+ reversed electron flow and succinate-driven energy-dependent transhydrogenation) are likewise markedly decreased, while ATP-driven energy-dependent transhydrogenation and mitochondrial ATPase are normal. Our data support the concept that iron deficiency leads to decreased electron-carrying capacity of iron-containing mitochondrial enzymes, with skeletal muscle being much more susceptible than liver, but that the mitochondria are otherwise normal with regard to energy conservation.

Adenine Nucleotides↗

PubMed1996

Increased antioxidant capacity, suppression of free radical damage and erythrocyte aggrerability after combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion in early postburn period in rats.

Certain rheological disorders such as enhanced aggregation and reduced deformability of erythrocytes are closely associated with microcirculatory disturbances, decreased tissue oxygen supply and represent a major problem in severely burnt patients [1-4]. Vitamin E (alpha-tocopherol) and vitamin A (retinol) exert an important plasma antioxidant properties against free radical-induced damage [11,12]. They possess chain-breaking properties and act as synergists [13]. Plasma antioxidant capacity may be decreased in severely burnt patients as a result of the enhanced consumption and inadequate restoration of antioxidants in the conditions of activated peroxidative process [14]. Treatment with alpha-tocopherol suppresses lipid peroxidation in blood and therefore improves erythrocyte rheology [15]. Perfluorocarbon emulsions improve microcirculation and rheological blood properties [16-18] and preserve the structure and function of endothelial cells [19]. The very small particle size, low viscosity and high oxygen carrying capacity ensure their penetration into the microvasculature even under conditions of ischemia and acidosis [20, 21]. Perfluorocarbons have been reported to inhibit leukocyte activation and superoxide radical production [22]. The aim of the present study was to examine the antioxidant capacity, free radical mediated damage and erythrocyte aggregation in plasma of rats with thermal skin injury in the early postburn period and to evaluate the effect of treatment with alpha-tocopherol and FC-43 perfluorocarbon emulsion alone and in combination. We might conclude that thermal skin injury in rats reduces the antioxidant capacity, enhances free radical mediated damage and erythrocyte aggregation on the third hour after injury. The combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion immediately after thermal skin injury in rats increases plasma antioxidant capacity, decreases free radical mediated damage of erythrocytes and suppresses their aggregation on the third hour after the injury.

Animals↗

PubMed1999

The effect of hyperoxaemia on erythropoietin secretion in anaemic patients.

Erythropoietin (EPO) controls red cell production. Hypoxaemia, reduced blood oxygen-carrying capacity and increased affinity of haemoglobin (Hb) for oxygen are the primary stimuli for EPO secretion. The effect of hyperoxaemia (arterial oxygen tension (Pa,O2) > 13.3 kPa) on EPO secretion has not been thoroughly studied and is not fully understood. The primary purpose of this study was to evaluate EPO production in patients with acute respiratory failure as well as to determine the effect of hyperoxaemia on EPO secretion in patients with and without anaemia. A prospective clinical study was carried out in a 14-bed general (medical and surgical) intensive care unit in a university hospital. Twenty-one patients with acute or acute on chronic respiratory failure, requiring mechanical ventilation, were included in this study. The patients were divided into two groups; group I comprised patients who developed anaemia, and group II patients who did not. EPO levels and haematological parameters were measured in venous blood under three oxygenation conditions: hypoxaemia, hyperoxaemia and normoxaemia. All patients exhibited high EPO levels during hypoxaemia (mean value 108.7 +/- 27 mU.mL-1 (+/- SD)). During hyperoxaemia, EPO levels decreased in both groups (mean value 21.6 +/- 15.2 mU.mL-1 in group I, 36.8 +/- 19 mU.mL-1 in group II). During normoxaemia, EPO levels increased again in group I patients, but in group II patients EPO production remained stable. In conclusion, hyperoxaemia inhibits erythropoietin secretion in spite of anaemia and low arterial oxygen tension. Hyperoxaemia may be a contributing factor to anaemia in intensive care unit patients under oxygen therapy.

Adult↗

PubMed1997

Isovolemic hemodilution with a bovine hemoglobin-based oxygen carrier: effects on hemodynamics and oxygen transport in comparison with a nonoxygen-carrying volume substitute.

OBJECTIVE: Stroma-free hemoglobin solutions have been shown to maintain oxygen transport in the absence of red blood cells. This study was designed to investigate the impact of such solutions on hemodynamics and oxygen transport during progressive isovolemic hemodilution within and even beyond a clinically relevant range of hematocrit values. DESIGN: Prospective, randomized experimental study comparing a bovine hemoglobin-based oxygen carrier (bHBOC) with a conventional nonoxygen-carrying volume substitute (hydroxyethyl starch [HES]). SETTING: Animal laboratory of a university cardiovascular research center. PARTICIPANTS: Splenectomized full-grown foxhounds, anesthetized with pentobarbital and piritramid. INTERVENTIONS: Twelve splenectomized foxhounds were anesthetized and mechanically ventilated. Catheters were placed for hemodilution, arterial and venous blood sampling, and hemodynamic measurements. The baseline hematocrit (Hct) value was adjusted to 0.35 by an initial isovolemic exchange of blood for identical volumes of HES (10% HES 200/0.5). Thereafter, the hematocrit was progressively reduced by isovolemic hemodilution using either HES (n = 6) or bHBOC (n = 6). MEASUREMENTS AND MAIN RESULTS: Hemodynamic and laboratory parameters of oxygen transport were measured at Hct values of 0.30, 0.20, and 0.10. Oxygen content was directly estimated using an oxygen-specific fuel cell. Arterial oxygen content at an Hct value of 0.10 nearly doubled in bHBOC-treated dogs as compared with HES-diluted animals (p < 0.001). This gain in oxygen-carrying capacity was completely negated by a decrease in cardiac output (-32% Hct 0.35 v Hct 0.30; p < 0.001) immediately on the first infusion of bovine hemoglobin. Thus, oxygen delivery was significantly lower as compared with HES-treated dogs at Hct 0.30 and 0.20, but remained stable at a level of 60% of baseline until Hct was 0.10. Both the pulmonary and the systemic vascular resistances increased. CONCLUSIONS: Isovolemic hemodilution with bHBOC did not improve systemic oxygen delivery in comparison with a nonoxygen-carrying diluent (HES) in a range of Hct values down to 0.10. Unchanged mixed venous lactate levels and stable oxygen consumption indicate sufficiently maintained oxygen delivery. This might become advantageous in patients who are unable to adequately increase cardiac output during hemodilution.

Animals↗

PubMed1997

[Safe levels of hemoglobin concentration in autologous blood transfusion].

It has been generally accepted that an adequate oxygen-carrying capacity can be achieved with a hemoglobin concentration of 7 g/dl, as far as the patient's intravascular volume is sufficient to allow tissue perfusion. To guarantee patient's safety in the operating theater, patient's oxygenation, ventilation, circulation and temperature, which enable oxygen utilization in tissues, should be monitored vigilantly and ensured strictly. This is also true when taking care of anemic patients outside the operating theater, because failure of these functions in anemic patients leads directly to tissue hypoxia. Besides the standard monitoring, measuring oxygen carrying capacity/consumption parameters and gastric/sigmoidal intramucosal pH have been shown to be helpful to estimate tissue oxygenation. Therefore, safe levels of hemoglobin concentration should be determined according to the ability of doctors and nursing staffs to evaluate and to maintain patient's systemic and tissue oxygenation as well as to the patient's pathophysiological conditions.

Anemia↗

PubMed1984

Carbon monoxide poisoning: mechanisms, presentation, and controversies in management.

Carbon monoxide (CO) remains the leading cause of death due to poisoning in the United States. CO produces toxicity by binding to hemoglobin, thereby reducing oxygen-carrying capacity, and by binding to myoglobin, which may impair cardiac output and result in cerebral ischemia. Severe CO poisoning results in coma or encephalopathy, but milder intoxication may occur with nonspecific symptoms suggestive of hysteria, hyperventilation, psychosis, or viral syndrome. Survivors of severe CO poisoning may have permanent neurologic or neuropsychiatric sequelae. Subtle memory deficits or personality changes may not be readily apparent to the examining physician. Administration of 100% oxygen at ambient pressure remains convenient, safe, and inexpensive. Hyperbaric oxygen can shorten the half-life of carboxyhemoglobin and can carry oxygen independent of hemoglobin. However, it is not known if either 100% oxygen or hyperbaric oxygen can actually alter mortality or improve neurologic outcome in survivors. Carefully controlled prospective studies should be carried out to assess the potential value of hyperbaric oxygen in CO poisoning.

Brain Edema↗

PubMed2000

Prediction of transdermal flux of prodrugs of 5-fluorouracil, theophylline, and 6-mercaptopurine with a series/parallel model.

Multiple regression analysis of fluxes from suspensions in isopropyl myristate (J(M)) as a function of molecular weights (MW) and solubilities in isopropyl myristate (S(IPM)) and water (S(AQ)) were performed on a data set of 41 compounds (n = 41) comprising 39 prodrugs of 5-fluorouracil (5-FU), theophylline (Th), and 6-mercaptopurine (6-MP), in addition to 5-FU and Th, using four models. Two series/parallel models have been developed that allow an aqueous-only path in parallel with a lipid-only path and with a lipid-aqueous series path for the permeation of solutes through skin: log J(M) = log ¿1/[1/(aS(LIPID) 10(PhiMW)) + 1/(bS(AQ)/MW(1/2))] + cS(LIPID)10(PhiMW) + dS(AQ)/MW(1/2)¿ where a, b, c, and d are coefficients for flux through the lipid and aqueous portions of the series path, the lipid-only path, and the aqueous-only path, respectively, and Phi is the dependence of diffusivity in lipid on MW. In the first series/parallel model, S(LIPID) was predicted by S(IPM), and in the second, solvatochromic series/parallel model, S(LIPID) was predicted by S(IPM)(k MW + Omegai) where Omega(i) is the sum of the solvatochromic terms alpha, beta, pi, and R(2), and k is the coefficient for the dependence of partitioning on MW. Using the n = 41 solutions, the coefficients for the aqueous-only path were very small or not different from zero in the two series/parallel models, so only two-path series/parallel models were compared with the solvatochromic and transformed Potts-Guy models where a homogeneous barrier to permeation was assumed. For each model, one compound at a time was omitted from the data set and new parameter estimates were obtained for these 41-1 solutions and used to predict log J(M) for the omitted compound. The average errors of prediction of log J(M) (experimental log J(M) - predicted log J(M)) for the four models were 0.134 for the series/parallel (r(2) = 0.937), 0.127 for the solvatochromic series/parallel (r(2) = 0.967), 0.150 for the solvatochromic (r(2) = 0.950), and 0.134 log units for the transformed Potts-Guy model (r(2) = 0.944). Thus, the solvatochromic series/parallel model provides fit and predictive ability comparable to or slightly superior to previous models that assumed homogeneity of the diffusional barrier to flux in the rate-determining step, provides further theoretical support against the existence of a high capacity aqueous-only path, and provides further insight into the physicochemical properties that should be incorporated into solutes to optimize their flux. Using the solvatochromic series/parallel model, the parameter estimates for the n = 41 solution were used to calculate the flux of each compound through the two paths. For compounds with log partition coefficients (K(IPM:AQ)) of <0.8, permeation was mostly by the lipid-aqueous series path; for compounds with log K(IPM:AQ) >1.0, permeation was mostly by the lipid-only path; the lipid-aqueous series path exhibited the higher carrying capacity. (c) 2000 Wiley-Liss, Inc.

Fluorouracil↗

PubMed1989

Analyzing variation in egg-to-adult viability in experimental populations of Drosophila melanogaster.

Selective culling in populations of most organisms is rank-order: individuals of low rank on a scale of potential fitnesses tend to be eliminated during early development, whereas surviving adults (whose number reflects the carrying capacity of the environment) are generally drawn from the distribution's upper end. Haldane pointed out [Haldane, J.B.S. (1932) The Causes of Evolution (Harper & Row, New York)] that selection which favors individuals in the upper tail of a composite distribution curve tends to favor members of the more variable of two populations, rather than members of a less variable one, even though the latter may possess the higher mean. In addition to reviewing earlier observations bearing on Haldane's argument, the present report describes an analysis of the comparative egg-to-adult viabilities of flies (Drosophila melanogaster) carrying combinations of second chromosomes obtained from one or another of eight experimental populations. Overall, the viabilities of flies carrying combinations of chromosomes one of which is shared (i/j vs. j/k) are as different as those of flies carrying combinations of independently sampled chromosomes (i/j vs. k/l). Episodes seemingly occurred within the populations during which flies carrying combinations that shared a chromosome differed more in their viabilities than flies carrying unrelated combinations. Such episodes could reflect the occurrence of selection of the sort described by Haldane.

Alleles↗

PubMed1994

Cardiovascular applications of fluorocarbons: current status and future direction--a critical clinical appraisal.

Alteration of normal blood flow to the heart may result in myocardial ischemia or infarction. Perfluorochemical emulsions offer a potential means to improve oxygenation of the heart during periods of hypoxia. The small particle size and linear disassociation curve of perfluorochemicals may result in greater oxygen delivery than blood particularly in severely diseased or damaged atherosclerotic vessels. Intracoronary Fluosol given during PTCA reduces the myocardial ischemia which occurs during balloon inflation. Although Fluosol does not prevent myocardial dysfunction during prolonged balloon inflations, new concentrated perfluorochemicals have increased oxygen delivery capacity and may have greater benefit. Experimentally, during coronary occlusions, perfluorochemicals promote higher oxygen tension in areas of ischemia and result in infarct size reduction. Reduction of oxygen free radicals has been proposed as the mechanism by which Fluosol exerts its ability to reduce infarct size. Clinical studies with Fluosol and thrombolytic therapy for treatment of acute myocardial infarctions are ongoing to assess ability to preserve myocardial function. Perfluorochemical cardioplegia can deliver oxygen during periods of cardiac arrest and may improve immediate post CPB myocardial function particularly in those patients with pre-existing left ventricular dysfunction. The oxygen-carrying capacity of perfluorocarbons and its unique properties offer great advantages to improve the treatment of cardiovascular diseases.

Angioplasty, Balloon, Coronary↗

PubMed1997

Red cell transfusion therapy in the critical care setting.

According to our own experience and published reports the frequency of red cell transfusion in intensive care units is in the range of 0.2 to 0.4 units per patient per day and is dependent upon the local strategy, the patients involved and the kind of surgery performed. The rationale for red cell transfusion is to maintain or restore the oxygen carrying capacity of the blood to avoid tissue hypoxia which occurs when oxygen delivery drops below a certain critical value. Besides bleeding, phlebotomy is also a significant source of blood loss in critically ill patients. According to several recent reviews and consensus articles there is no basis for a fixed indicator for transfusion, such as a haemoglobin concentration of < 100 gL-1. The decision to transfuse has to be made according to the patients individual status. The major adaptive mechanism in response to acute anaemia is an increase in cardiac output and hence blood flow to tissues. As a consequence even moderate degrees of acute anaemia may not be tolerated by patients with cardiac disease, whilst marked anaemia carries a considerable risk of ischaemia in patients with brain lesions or cerebral arterial stenoses. In critically ill patients it has been postulated that supply dependency of oxygen consumption occurs over a wide range of oxygen delivery, far above the critical values of oxygen delivery seen under normal conditions. Maximising oxygen delivery was therefore formulated as a goal in these patients. However, whether pathological supply dependency of oxygen delivery really exists in critically ill patients is still under discussion and recent studies found no benefit in maximising oxygen delivery to this patient group. However, individualised triggers for red blood cell transfusion are adequate for critically ill patients considering their co-morbidities and severity of disease. Finally, the decision to transfuse must also take into account the potential risks (infectious and non-infectious), as well as benefits for the individual patient. In the future, the level of transfusions may be reduced by using blood sparing techniques such as blood withdrawal in closed systems, bedside microchemistry, intravascular monitors, or autotransfusion of drainage blood in intensive care units.

Adaptation, Physiological↗