Effect of blood flow on gas transport in a pulmonary capillary

The effects of blood velocity on gas transport within the alveolar region of lungs, and on the lung diffusing capacity DL have for many years been regarded as negligible. The present work reports on a preliminary, two-dimensional investigation of CO convection-diffusion phenomenon within a pulmonary capillary. Numerical simulations were performed using realistic clinical and morphological parameter values, with discrete circular red blood cells (RBCs) moving with plasma in a single capillary. Steady-state simulations with stationary blood (RBCs and plasma) were performed to validate the model by comparison with published data. Results for RBCs moving at speeds varying from 1.0 mm/s to 10 mm/s, and for capillary hematocrit (Ht) from 5% to 55%, revealed an increase of up to 60% in DL, as compared to the stationary blood case. The increase in DL is more pronounced at low Ht (less than 25%) and high RBC speed and it seems to be caused primarily by the presence of plasma. The results also indicate that capillary blood convection affects DL not only by improving the plasma mixing in the capillary bed but also by replenishing the capillary with fresh (zero concentration) plasma, providing an additional reservoir for the consumption of CO. Our findings cast doubt on the current belief that an increase in the lung diffusing capacity of humans (for instance, during exercising), with fixed hematocrit, can only be accomplished by an increase in the lung volume effectively active in the respiration process.     

About a correlation between calcium ion concentration (Ca2+) in the blood and the state of physiological functions in animals in deep cooling

The changes in physiological functions of the organism (respiration, functions of the heart and vessels, thermoregulation) were studied. The concentration of Ca2+ ions in the blood of white rats was determined by the ion-selective electrodes at various stages of hypothermia. The aim of the study was to reveal changes in the blood concentration of ionized calcium in animals during their gradual cooling. In deep hypothermia (16 degrees C), calcium ion concentration in the blood increased by 30% against the norm which coincides with arrest of the cold shivering and lung ventilation. An increased content of Ca2+ in the blood is supposed to result in an increase in the content of these ions in the intercellular liquid and in the nervous cells, which is one of the reasons for the cold paralysis of the respiration and thermoregulation centers.     

Respiration and sodium transport in rabbit urinary bladder

Respiration of rabbit urinary bladder was measured in free-floating pieces and in short-circuited pieces mounted in an Ussing chamber. Ouabain, amiloride, and potassium-free saline inhibited respiration approx. 20%; sodium-free saline depressed respiration approx. 40–50%. The coupling ratio between respiration and transport in short-circuited tissues was about two sodium ions per molecule O₂. Chloride-free saline depressed mean oxygen consumption 21% in free-floating tissue pieces; 4-acetamido-4′-isothiocyanostilbene-2,2′-disulfonic acid (SITS) and furosemide had no effect. The effect of chloride-free saline in short-circuited tissues was variable; in tissues with low transport rates, respiration was stimulated about 21% while in tissue with high transport rates respiration was reduced about 24%. Nystatin and monensin, both of which markedly increase the conductance of cell membranes with a concomitant increase in sodium entry, stimulated respiration. These data indicate that 50–60% of the total oxygen consumption is not influenced by sodium, 20–25% is linked to (Na⁺ + K⁺)-ATPase transport, while the remaining 25–30% is sodium-dependent but not ouabain-inhibitable.     

Changes of gas exchange parameters and of functional-biochemical properties of erythrocytes in dynamics of experimental anemia in rats

In experiments on male Wistar rats, in a specially constructed computerized installation, O₂ consumption by the animals in comparison with changes of hematological, biochemical, and rheological blood properties is studied after anemization—acute blood loss (12–15% of the total blood mass). An increase of the O₂ consumption by the organism and tissues by 18–28% has been revealed for the first 7 days after the blood loss, in spite of a pronounced decrease of hematocrit and of the amount of erythrocytes and hemoglobin in peripheral blood by 20–25% of the initial level. There was a 5–10-fold increase of the content of immature erythrocyte forms—reticulocytes and a progressive rise of cell acidic resistance, which is characteristic of young erythrocyte forms. An increase of O₂ consumption at a decrease of the blood oxygen capacity (a low hemoglobin level) seems to be due to the more efficient transport and yield of O₂ to tissues. At the 3rd and 7th day after the blood loss, activity of Na,K-ATPase has been found to increase by 60% and 20%, respectively. Analysis of the erythrocyte rheological properties has shown that the maximal firmness of aggregates (U_q) and the aggregation rate (1/T) decrease progressively beginning from 3 days after the blood loss; index of deformability (I_max) turned out to be elevated by 7–11%, probably due to an increase of the cell membrane elasticity. The conclusion is made that changes of erythrocyte rheological properties are interconnected with changes of the Na,K-ATPase activity and are directed at optimization of blood circulation in large vessels and the capillary network.     

Polymerized bovine hemoglobin decreases oxygen delivery during normoxia and acute hypoxia in the rat

Hemoglobin-based oxygen carriers (HBOC) have been primarily studied for blood loss treatment. More recently infusions of HBOC in euvolemic subjects have been proposed for a wide variety of potential therapies in which increased tissue oxygenation would be beneficial. However, compared with the exchange transfusion models to study blood loss, less is known about HBOC oxygen delivery and vasoacitvity when it is infused in euvolemic subjects. We hypothesized that HBOC [polymerized bovine hemoglobin (PBvHb)] infusion creating hypervolemia would increase oxygen delivery to tissues during acute global hypoxia. Vascular oxygen content and hemodynamics were determined after euvolemic rats were infused with 3 ml of either lactated Ringer or PBvHb solution (13 g/dl, 1.3 g/kg) during acute hypoxia (FIO2 = 10%, 4 h) or normoxia (FIO2 = 21%) exposure. Our data demonstrated that compared with Ringer-infused animals, in hypoxia and normoxia, PBvHb treatment improved oxygen content but raised mean arterial pressure, lowered stroke volume, heart rate, and cardiac index, which resulted in a net reduction in blood flow and oxygen delivery to the tissues. The PBvHb vasoactive effect was similar in magnitude and direction as to the Ringer-infused animals treated with a nitric oxide synthase inhibitor nitro-l-arginine, suggesting the PBvHb effect is mediated via nitric oxide scavenging. We conclude that infusion of PBvHb is not likely to be useful in treating global hypoxia under these conditions.     

Towards a novel haemoglobin-based oxygen carrier: Euro-PEG-Hb, physico-chemical properties, vasoactivity and renal filtration

Blood transfusion is still a critical therapy in many diseases, traumatic events and war battlefields. However, blood cross-matching and storage may limit its applicability, especially in Third World countries. Moreover, haemoglobin, which in red blood cells is the key player in the oxygen transport from lung to tissues, when free in the plasma causes hypertension and renal failure. This investigation was aimed at the development of a novel haemoglobin-based oxygen carrier with low vasoactivity and renal filtration properties. Human haemoglobin was chemically conjugated with polyethylene glycol (PEG) under either aerobic or anaerobic conditions, following different chemical procedures. The resulting PEGylated haemoglobin products were characterized in terms of oxygen affinity, cooperativity, effects of protons and carbon dioxide concentration, and oxidation stability, and were transfused into rats to evaluate vasoactivity and renal filtration. A deoxyhaemoglobin, conjugated with seven PEG and seven propionyl groups, which we called Euro-PEG-Hb, did not produce profound hypertension, was 99% retained within 6 h, and exhibited oxygen binding properties and allosteric effects more similar to human haemoglobin A than the other tested PEGylated haemoglobin derivatives, thus appearing a very promising candidate as blood substitute.     

A comparison of the insulin-sensitive transport of chromium in healthy and model diabetic rats

In response to insulin, chromium(III) is moved from the blood to the tissues where it is ultimately lost in the urine, apparently as the oligopeptide chromodulin; this transfer of chromium is mediated by the protein transferrin. To examine the effects of type 1 and type 2 diabetes on the transport of chromium, the fate of chromium from intravenously introduced (51)Cr(2)-labelled transferrin was monitored after 2 h in healthy and diabetic model rats; the effects of insulin on the transport of chromium in these groups were also examined. Diabetic rats had greater urinary chromium loss, greater movement of chromium from the blood to the tissues, most notably to the skeletal muscle, and an alteration of the distribution of chromium in the blood plasma.     

Oxygen Transport System in Children Living in the Russian Far North

We studied 654 healthy ten- to twelve-year-old children living in the Russian Far North (Taimyr peninsula) and in Siberia (town of Krasnoyarsk). The state of the body oxygenation and the systems responsible for oxygen delivery were studied according to the length of time living in the Russian Far North and season of the year. An examination of newcomer children revealed the following changes during the first year of living in the Russian Far North: an increased respiration rate and changes in its circadian rhythm; an increase in the heart rate, cardiac output, and cardiac index; an increase in the mean corpuscular volume in the red blood system; the activation of lipid peroxidation, and the changes in electrolyte balance of cells. The control mechanisms of oxygen transport system gradually stabilized during the ages of two to five years. In children living more than five years in the Russian Far North, the increased oxygen demand was met by the activation of cardiovascular and red blood systems aimed at more effective and adequate oxygen delivery to tissues.     

Inosine metabolism in the rat

1. Uptake and subsequent metabolism of purine and ribose moieties was monitored after intravenous administration of doubly labelled inosine. 2. More than 95% was cleared from the plasma within 5 min, and 99% within 20 min. 3. Approx. 50% of the 160 mumol total was rapidly incorporated into liver and kidney. Kidney removed the greatest amount (21 mumol/g wet wt.), about 10-fold more than heart, lung or liver. Lung and heart accounted for only 3%. These tissues then lost radioactivity during the remainder of the experiment. Radioactivity in the skeletal muscle, in contrast, increased from 8% of the injected dose at 5 min to 40% at 60 min. 4. In liver, kidney, heart and lung there was a significant difference in the fate of inosine. After initial incorporation of inosine, kidney predominantly lost inosine; heart preferentially lost purines; lung preferentially lost ribose radioactivity; and in liver the ribose radioactivity was rapidly lost, whereas purine was retained. Some of the ribose moiety was metabolized to glucose, presumably in the liver, and then released into the blood. Ribose radioactivity (probably as glucose) and radioactive hypoxanthine accumulated in skeletal muscle throughout the experiment. 5. Inosine caused a rapid and prolonged increase in the blood glucose content, from 6 to 15 mM in 60 min. This was accompanied by a small increase in plasma insulin. 6. It is concluded that the purine and ribose radioactivity lost from the kidney, liver and other tissues becomes incorporated into skeletal muscle.     

Lysosomal apparatus of some body tissues in hemorrhage-induced hypoxia ]

The experiments on 40 Wistar male rats with acute circulatory-hemic hypoxia induced by hemorrhage in amount of 15-20% of circulating blood volume were carried out to study the state of lysosomal apparatus of the liver and lung tissues as to changes in activity of acid phosphatase (AP), a marker enzyme of lysosomes. In the case of such a hemorrhage the common activity of AP decreased by 37% in the liver tissue and by 41% in the lung tissue, the free activity increased by 30% and 25%, and bound activity decreased by 84 and 70% in homogenates of the corresponding tissues. Under these conditions the activity of the above lysosomal enzyme in blood plasma became five times as higher as control. A conclusion is made concerning the circulatory-hemic hypoxia influence on the lysosomal membrane's structures of organ's tissues cells (as one can judge by the example of liver and lungs), which is observed in an increase of permeability of lysosome membrane and causes a sharp increase of AP enzymia in blood plasma.     

Acute volume expansion as a physiological stimulus for the release of atrial natriuretic peptides in the rat

The concentration of immunoreactive atrial natriuretic peptide(s) (ANP) was measured in normovolemic conscious rats and 15 min after 10% and 20% blood volume expansion. A 20% blood volume expansion caused a 2-fold increase in plasma ANP. While plasma ANP increased linearly, atrial levels of ANP remained unaltered. The increase in plasma ANP parallelled increases of central blood volume and central venous pressure. It is concluded that acute blood volume expansion is a major physiological stimulus for the release of atrial natriuretic peptides into the circulation.     

ATP Accelerates Respiration of Mitochondria From Rat Lung and Suppresses Their Release of Hydrogen Peroxide

Lung mitochondria were isolated by differential centrifugation from pentobarbital-anesthetized male rats. One to three millimolar Mg²⁺-ATP increased the consumption of oxygen of lung mitochondria oxidizing 10 mM succinate > fourfold (P < 0.01) whereas ATP increased the respiration of liver mitochondria by < 35%. ATP also hyperpolarized partially uncoupled lung mitochondria in the presence of the mitochondria-specific antagonist, oligomycin. However, only 20% of the ATPase activity in the lung mitochondria was blocked by oligomycin compared to a blockade of 91% for liver mitochondria. We investigated the effect of reducing the non-mitochondrial ATPase activity in the lung preparation. A purer suspension of lung mitochondria from a Percoll gradient was inhibited 95% by oligomycin. The volume fraction identified as mitochondria by electron microscopy in this suspension (73.6± 3.5%) did not differ from that for liver mitochondria (69.1± 4.9%). ATP reduced the mean area of the mitochondrial profiles in this Percoll fraction by 15% (P <0.01) and increased its state 3 respiration with succinate as substrate by 1.5-fold (P < 0.01) with no change in the state 4 respiration measured after carboxyatractyloside. Hence, ATP increased the respiratory control ratio (state 3/state 4, P <0.01). In contrast, state 3 respiration with the complex 1-selective substrates, glutamate and malate, did not change with addition of ATP. The acceleration of respiration by ATP was accompanied by decreased production of H₂O₂. Thus ATP-dependent processes that increase respiration appear to improve lung mitochondrial function while minimizing the release of reactive oxygen species.     

Adipose, muscle and lung tissue lipoprotein lipase activities in young streptozotocin treated rats

Lipoprotein lipase (LPL) activity was studied in adipose, muscle and lung tissues of post-weanling rats 48 and 96 hours after experimentally induced diabetes by streptozotocin administration. Weight gain was reduced, and blood glucose level increased about 3-4 fold above the control level as an indication of the diabetic state. LPL activity in brown and white adipose tissues decreased in diabetic rats to 10-30% of the control level. In soleus muscle the LPL activity was slightly enhanced 96 hours after the streptozotocin injection. In cardiac muscle the LPL activity was markedly increased already 48 hours after the administration of streptozotocin and the increase remained significant until 96 hours. There was in the pulmonary tissue also an increase of LPL activity of diabetic rats, although this was significant only 96 hours after streptozotocin treatment. The results suggest marked tissue specific variation in the LPL activity. Moreover, tissue responses to experimentally induced diabetes vary. In adipose tissue the decrease in the LPL activity suggests that lipid transport to adipocytes is decreased while an increase in skeletal and cardiac muscles and in lung tissue proposes that their lipid utilization is enhanced.     

Mitochondrial respiration and oxygen transport during various stages of lung inflammation

It is shown in rats with experimental lung inflammation that the phosphorylative and uncoupling mitochondrial respiration intensity rises at acute and reverses to the normal level at subacute inflammation. At chronic inflammation the 2,4-DNP-stimulated mitochondrial respiration enhances and the ADPO coefficient lowers. At all stages of inflammation the pO2 rise in muscles after O2-inhalation is less than in healthy animals. The disturbance of O2 transport in organism may be the reason of the described low energy shift at lung inflammation.     

Cardiovascular responses to acute, severe haemorrhage in fetal sheep

In adults, the responses to acute haemorrhage vary greatly depending on the amount of blood lost. While many studies have documented fetal responses to mild haemorrhage, fetal responses to severe haemorrhage are not known. In this study we examined the effect of acute, severe haemorrhage in fetal lambs. Despite the severity of haemorrhage, we found that mean arterial blood pressure was restored within 2 min, and heart rate was restored within 30 min. This restoration of blood pressure and heart rate was facilitated by an increase in peripheral vascular resistance mediated in part by secretion of catecholamines and plasma renin. In addition, about 40% of the shed blood volume was restored within 30 min by fluid from either the fetal interstitium or placenta. The PO2 of umbilical venous blood increased from 33 +/- 9 mmHg to 49 +/- 17 mmHg 2 min post-haemorrhage, and to 47 +/- 15 mmHg 30 min post-haemorrhage. However, this increase was not sufficient to offset the fall in both haemoglobin concentration and umbilical-placental blood flow, so that oxygen delivery decreased from 21.1 +/- 5.5 ml/min per kg to 9.1 +/- 5.2 ml/min per kg 2 min post-haemorrhage, and 14.1 +/- 9.2 ml/min per kg 30 min post-haemorrhage. Because of this decrease in oxygen delivery, oxygen consumption fell and a metabolic acidemia ensued. Nevertheless, oxygen delivery to the heart and brain was maintained because hepatic vasoconstriction diverted more of the well oxygenated umbilical venous return through the ductus venosus. Although the fetus was able to tolerate acute loss of 40% of blood volume, larger volumes of haemorrhage resulted in fetal death.     

Changes of physiological and biochemical characteristics of rat erythrocytes after blood loss

In experiments of Wistar male rats, changes are studied of erythrocyte hematological, biochemical (activitities of transport ATPases), and rheological properties (capability for aggregation and deformability) 7 days after bloodletting of 12-15 % of the total blood mass. It has been shown that alongside with an elevation of erythrocyte volume and of the number of immature cells - reticulocytes, there was a statistically significant increase of Na,K-ATPase and Ca-ATPase activities in the whole erythrocytes and their membrane preparations - ghosts, the increment of activity in the case of Na,K-ATPase being essentially higher in the whole cells. This indicates the appearance of an enzyme activator inside the erythrocytes. There are also revealed a decrease of firmness of erythrocyte aggregates, a deceleration of spontaneous aggregation, and an increase of index of erythrocyte deformability. The conclusion is made that changes of erythrocyte rheological properties are interconnected with changes of the Na,K-ATPase activity and are directed to optimization of blood circulation in large vessels and capillary network.     

Individual specifics of oxygen consumption by the human organism in hypoxia

Influence of hypoxia on a human organism was studied with the help of hypoxic gas mixtures (HGM) in the first series with 14 % content of oxygen in nitrogen (n = 6), in the second one--with 12 % (n = 10) in the third one--with 8 % (n = 14). Hypoxic exposition in all the series was 25 min. In 6 subjects engaged in all the 3 series, physical working capacity was assessed in two-step test on a veloergometer. In all the 3 series, oxygen consumption by the organism some time after the start of the hypoxic action exceeded the background normnoxic level. Maximal value of this excess on the average was the highest in HGM-12 series--40 +/- 12 %. Maximal increase of the respiration and central blood circulation velocity was the highest in HGM-8 series, 90 +/- 24 and 25 +/- 16 % respectively. Analysis of the EEG parameters, oxygen saturation and rheoencephalographic data indicates the probability of the cerebral metabolic rate of oxygen during hypoxia to beein normal (in most subjects) and even increased (in some subjects). In 3 subjects of 6, whose physical working capacity was assessed, maximal increase of oxygen consumption was observed in HGM-8 series--105 +/- 34 %. Their physical working capacity was higher than of those subjects, who showed maximal increase of oxygen consumption in HGM-12 series. Analysis of increase in oxygen consumption (paradoxical under hypoxic conditions) doesn't allow to ascribe it wholly to an increase of the respiration and central blood circulation. Obviously, the increase of oxygen and energy expenditures for biochemical adaptation to hypoxia, which has common features with adaptation to physical activity plays an important role under hypoxia.     

Hepatic respiratory compensation and blood volume in the frog (Rana esculenta)

In the frog, Rana esculenta (L.), the liver can change in volume by over 25%, depending on the respiratory conditions of the animal: in well-oxygenated specimens the organ can hoard about half of the total amount of erythrocytes in its sinusoids, and release them into the bloodstream under conditions of hypoxia. This phenomenon can be observed at a temperature of 6°C by comparing the liver volumes and haematic values of chlorobutanol-anaesthetized animals exposed to the air or submerged in still water (a condition which induces hypoxia): the blood volume remains constant, at about 5 ml per 100g of body weight, but red blood cell count and haematocrit value differ by as much as 50%. At 18°C there is an increase in oxygen demand and in anaesthetized animals, which rely totally on cutaneous respiration, the compensatory liver mechanism can no longer be observed, since all the available erythrocytes are already circulating in a blood volume which, depending on respiratory conditions, can vary between about 7 and 8ml/100g. At 30°C, cutaneous respiration alone does not allow the anaesthetized animals to survive long enough to stabilize their haematic parameters.     

Brain oxygen transport related to levels of fetal haemoglobin in stable preterm infants.

The relative amount of regional cerebral oxygen transport was compared between different preterm infants by performing measurements of cerebral blood flow velocity, mean arterial blood pressure, whole blood viscosity and haemoglobin content for each individual. In addition the percentage of fetal haemoglobin was determined. On 25 occasions measurements of fetal haemoglobin and cerebral oxygen transport have been performed prior to and following a blood transfusion with adult red blood cells. Comparison of the data for cerebral oxygen transport suggests that the actual amount of cerebral oxygen transport is lowest at fetal haemoglobin levels below 30% and will increase progressively as soon as the percentage of fetal haemoglobin rises about 30%. Thus, at increasing fetal haemoglobin levels, cerebral haemodynamic mechanisms in the human neonate cause elevations of regional cerebral blood flow and oxygen transport. The found increase of cerebral blood flow and oxygen transport at high fetal haemoglobin levels will minimize the impeded dissociation and delivery of oxygen to brain tissues.     

Changes of physiological and biochemical characteristics of rat erythrocytes after blood loss

In experiments on Wistar male rats, changes are studied of erythrocyte hematological, biochemical (activities of transport ATPases), and rheological properties (capability for aggregation and deformability) 7 days after bloodletting of 12–15% of the total blood mass. It has been shown that alongside with an elevation of erythrocyte volume and of the number of immature cells—reticulocytes, there was a statistically significant increase of Na,K-ATPase and Ca-ATPase activities in the whole erythrocytes and in their membrane preparations—ghosts, the increment of activity in the case of Na,K-ATPase being essentially higher in the whole cells. This indicates the appearance of an enzyme activator inside the erythrocytes. There are also revealed a decrease of firmness of erythrocyte aggregates, a deceleration of spontaneous aggregation, and an increase of index of erythrocyte deformability. The conclusion is made that changes of erythrocyte rheological properties are interconnected with changes of the Na,K-ATPase activity and are aimed at optimization of blood circulation in large vessels and capillary network.