Rheological of blood and oxygen transport in long-term adaptation to muscular load

The blood viscosity became reduced after a long-term muscular adaptation in dogs. The main adaptation mechanism is associated with an autoregulated haemodilution and improvement of the red blood cells' microrheology (deformities and aggregation). The findings suggest that reduction in the haemodilution and the blood oxygen capacity are accompanied by a heightened efficiency of the oxygen transport. A sufficient correlation exists between the blood fluidity parameters and the oxygen balance in the body. Value of the optimum haematocrit in oxygen transport, is discussed.     

Effect of endurance flight on haematocrit in migrating birds

The effects of an endurance flight on the haematocrit, the percentage of packed red blood cells per blood volume, were examined within the framework of six possible factors explaining possible changes in the haematocrit. Two approaches were adopted: (1) the haematocrit was studied in four species of passerine birds which landed on an Italian island after having crossed the Mediterranean Sea on their spring migration in a non-stop flight; (2) the haematocrit was evaluated in six individual red knots after a flight of 1, 2, 4 and 10 h in a wind tunnel and the data thus obtained compared with data on resting birds with or without food. In the four passerine species, the haematocrit decreased from 51% in fat birds to 48% in lean birds. In lean birds, the haematocrit dropped from 48% in birds with well-developed breast muscles to 36% in birds with emaciated breast muscles. In the red knots, the haematocrit was dependent on body mass in flying and resting birds. The haematocrit decreased from about 51% pre-flight to about 49% within 1 h of flight and remained at this level for up to 10 h of flight. Taking the results from the passerines and the red knots together, it seems that the haematocrit drops by a few percentage points within 1 h after the onset of flight, decreases very slowly with decreasing body mass and decreases more steeply in very lean birds having entered stage III of fasting. This indicates that dehydration is not an underlying factor in decreased haematocrit because if this were the case we would expect an increase with endurance flight. We found no effect of the presence of blood parasites on haematocrit. With the onset of flight, haemodilution may be adaptive, because it reduces blood viscosity and, thereby, energy expenditure by the heart, or it may be a sign of water conservation as an insurance against the risk of dehydration during long non-stop flights. During endurance flight, a reduction in the haematocrit may be adaptive, in that oxygen delivery capacity is adjusted to the decreased oxygen needs as body mass decreases. A decreasing haematocrit would also allow birds to reduce heart beat frequency and/or heart size, because blood viscosity decreases disproportionally with decreasing haematocrit. However, when energy stores are about to come to an end and birds increase protein breakdown, the haematocrit decreases even further, and birds probably become anaemic due to a reduced erythropoiesis.     

Early fluid and protein shifts in men during water immersion

High precision blood and plasma densitometry was used to measure transvascular fluid shifts during water immersion to the neck. Six men (28-49 years) undertook 30 min of standing immersion in water at 35.0 +/- 0.2 degrees C; immersion was preceded by 30 min control standing in air at 28 +/- 1 degrees C. Blood was sampled from an antecubital catheter for determination of blood density (BD), plasma density (PD), haematocrit (Ht), total plasma protein concentration (PPC), and plasma albumin concentration (PAC). Compared to control, significant decreases (p less than 0.01) in all these measures were observed after 20 min immersion. At 30 min, plasma volume had increased by 11.0 +/- 2.8%; the average density of the fluid shifted from extravascular fluid into the vascular compartment was 1006.3 g.l-1; albumin moved with the fluid and its albumin concentration was about one-third of the plasma protein concentration during early immersion. These calculations are based on the assumption that the F-cell ratio remained unchanged. No changes in erythrocyte water content during immersion were found. Thus, immersion-induced haemodilution is probably accompanied by protein (mainly albumin) augmentation which accompanies the intravascular fluid shift.     

Changes in arterial blood pressure, heart rate and haematocrit during acute hyperkalaemia in conscious sheep.

The systolic, diastolic and mean arterial blood pressures, heart rate and haematocrit were measured at 15 minute intervals before, during and after 2 hour infusions of 0-4 mol.l-1 NaCl at 2-2 ml min-1 into conscious intact sheep and 0-4 mol. l-1 KCl at 2-2 ml. min-1 into conscious sheep which were either intact or adrenalectomized. The haemotocrit was also measured in splenectomized sheep receiving 0-4 mol. l-1 KCl. The NaCl infusion had no significant effect on blood pressure(BP), heart rate and haematocrit. Both intact and adrenalectomized sheep were able to withstand an increase in plasma potassium concentration in excess of 50% of the preinfusion concentration before any substantial fall in BP occurred. In intact and adrenalectomized sheep, heart rate and haematocrit increased rapidly and progressively throughout the potassium infusions and at maximum plasma potassium concentration the mean increments in these parameters for both groups of sheep were 21-6+/-2-69 beats/min and 7-5+/-0-47% respectively. Heart rate and haematocrit were more closely correlated with the plasma potassium concentration than with any other variable measured in these experiments. Adrenalectomy did not reduce the ability of the sheep to maintain their BP or to increase their heart rate and haematocrit. As the mean increase in haematocrit during potassium infusion into splenectomized sheep was 1-3+/-0-45% most of the increase in haematocrit observed in the potassium-infused intact and adrenalectomized sheep was caused by ejection of red cells from the spleen into the circulation.     

Influence of prolonged physical exercise on the erythropoietin concentration in blood

Erythropoietin (EPO) and red blood cells were studied in 15 well-trained men before and several times after a marathon run. Changes in red blood cells reflected changes of plasma volume. Immediately after the run, red blood cells were increased due to haemoconcentration, whereas 31 h later the values were decreased due to haemodilution. The EPO concentration was increased 3 h, and more impressive 31 h, after the run. This long-lasting increase in EPO concentration after the marathon run would seem to be responsible for the increased red blood cell mass in long distance runners.     

Haematological, blood gas and acid-base effects of central histamine-induced reversal of critical haemorrhagic hypotension in rats.

In a rat model of volume-controlled irreversible haemorrhagic shock, which results in a severe metabolic acidosis and the death of all control animals within 30 min., intracerebroventricular injection of histamine (100 nmol) produces a prompt and long-lasting increase in mean arterial pressure and heart rate, with a 100% survival of 2 h after treatment. Histamine action is accompanied by a decrease in haematocrit value, haemoglobin concentration, erythrocyte and platelet count, and an increase in residual blood volume at the end of the experiment (2 h). Cardiovascular effects are also associated with a long-lasting rise in respiratory rate and biphasic blood acid-base changes - initial increase of metabolic acidosis with the decrease in arterial and venous pH, bicarbonate concentration and base excess, followed by almost a complete recovery of blood gas and acid-base parameters to the pre-bleeding values, with normalisation of arterial and venous pH, Pco2 bicarbonate concentration and base excess at the end of experiment. It can be concluded that in the late phase of central histamine-induced reversal of haemorrhagic hypotension there is almost a complete restoration of blood gas and acid-base status due to circulatory and respiratory compensations, while accompanying haematological changes are the result of the haemodilution and the increase in residual blood volume.     

Changes in plasma volume and haematocrit in intact and splenectomized sheep during feeding.

Changes in jugular haematocrit during daily 2-h feeding periods in trained sheep with and without spleens were compared with changes in the concentration of the plasma tracer radio-iodinated human serum albumin. Jugular haematocrit was increased by 16% in intact sheep and 9% in splenectomized sheep 20 min after they started to eat dry rations. The dilution of tracer in plasma, studied after mixing in the vascular system had been completed, showed four phases. Phase 1 was the rate of removal of tracer in the period before eating began. Phase 2 was the sudden increase in plasma radioactivity that occurred in the first 20 min of eating, indicating a loss of plasma from the circulation. Phase 3 was the decrease in tracer concentration during the remaining feeding period and phase 4 was a post-feeding phase, characterized by a slower rate of decrease of tracer than during phase 3, implying that there was significant recycling of tracer during this phase. The sudden increase in plasma radioactivity, initiated by the onset of feeding, represented a reduction in plasma volume of 10-12%. Minimum plasma volume coincided with peak haematocrit values. The reduced plasma volume accounted for the increased haematocrit in splenectomized sheep, but only accounted for about half of the increase in intact sheep. The residual increase in haematocrit in intact sheep was most likely the result of splenic contraction.     

Detrimental effect of hypothermia during acute normovolaemic haemodilution in anaesthetized cats

 Haemodynamic responses to hypothermia were studied at normal haematocrit and following the induction of acute normovolaemic haemodilution. Experiments were performed on 20 cats anaesthetized with a mixture of chloralose and urethane in two groups. In one group (n=10) the effects of hypothermia on various haemodynamic variables were studied at normal haematocrit (41.0±1.7%) and in the second group of cats (n=10) the effects of hypothermia on various haemodynamic variables were studied after the induction of acute normovolaemic haemodilution (14.0±1.0%). The haemodynamic variables left ventricular pressure, left ventricular contractility, arterial blood pressure, heart rate and right atrial pressure were recorded on a polygraph. Cardiac output was measured using a cardiac output computer. In both groups hypothermia was induced by surface cooling with the help of ice. Cardiovascular variables were recorded at each 1° C fall in body temperature. Hypothermia produced a significant (P<0.05) drop in heart rate, cardiac output, arterial blood pressure and left ventricular contractility in both groups. However, the percentage decrease in these variables in response to hypothermia was significantly (P<0.05) higher in cats with low haematocrit than in those with normal haematocrit. The severity of hypothermia – induced cardiovascular effects is evident from the drastic decrease in heart rate, cardiac output, arterial blood pressure and myocardial contractility in cats with low haematocrit, indicating a higher risk of circulatory failure under anaemic conditions at low temperatures. Received: 21 October 1996 / Revised: 20 April 1997 / Accepted 21 May 1997     

Effects of acute exercise and prolonged exercise training on blood pressure, vasopressin and plasma renin activity in spontaneously hypertensive rats

The purpose of this study was to investigate the effect of swimming training on systolic blood pressure (BPs), plasma and brain vasopressin (AVP), and plasma renin activity (PRA) in spontaneously hypertensive rats (SHR) during rest and after exercise. Resting and postexercise heart rate, as well as blood parameters such as packed cell volume (PCV), haemoglobin concentration (Hb), plasma sodium and potassium concentrations ([Na+], [K+]) osmolality and proteins were also studied. Hypophyseal AVP had reduced significantly after exercise in the SHR, whereas PRA had increased significantly in the Wistar-Kyoto (WKY) strain used as normotensive controls. Plasma AVP concentration increased in both strains. By the end of the experiment, training had reduced body mass and BPs by only 10% and 6%, respectively. Maximal oxygen uptake was increased 10% and plasma osmolality 2% by training. The postexercise elevation of heart rate was not significantly attenuated by training. A statistically significant reduction in postexercise plasma osmolality (10%) and [Na+] (4%) was observed. These results suggested that swimming training reduced BPs. Plasma and brain AVP played a small role in the hypertensive process of SHR in basal conditions because changes in AVP contents did not correlate with those of BPs. Moreover, there were no differences between SHR and WKY in plasma, hypophyseal and hypothalamic AVP content in these basal conditions. Finally, during moderate exercise a haemodilution probably occurred with an increase of plasma protein content. This was confirmed by the exercise-induced increase of plasma AVP and the reduction of hypophyseal AVP content, suggesting a release of this hormone, which probably contributed to the water retention and haemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood rheology of Antarctic fishes: viscosity adaptations at very low temperatures

Viscosity of whole blood and plasma from Antarctic fishes were compared over a temperature range of −1.5 to 5°C; human samples and water provided reference values. Blood viscosity of nototheniids was greater than that of the haemoglobinless icefish, reflecting differences in packed cell volume, being 5.27 v. 3.27 cP at 0°C for Notothenia coriiceps and Chaenocephalus aceratus , respectively. The reduction in MCHC, rather than haematocrit, in nototheniids suggests that selection pressure has not acted at the level of oxygen transport. However, icefish plasma viscosity was similar to human, but greater than that of Notothenia spp., suggesting that viscometric influences on cardiac afterload may be adaptive for the latter. Indeed, handling stress induced a significant increase in viscosity of both whole blood and plasma which may impair cardiovascular performance. Such a response was not observed in icefish, and in view of the large blood vessels it is unlikely that viscosity plays any significant role in limiting activity of this species.     

The efficacy of field techniques for obtaining and storing blood samples from fishes

Prompted by the dramatic increase in the use of blood analyses in fisheries research and monitoring, this study investigated the efficacy of common field techniques for sampling and storing blood from fishes. Three questions were addressed: (1) Do blood samples taken via rapid caudal puncture (the ‘grab‐and‐stab’ technique) yield similar results for live v. sacrificed groups of fishes? (2) Do rapidly obtained caudal blood samples accurately represent blood properties of fishes prior to capture? (3) Does storage of whole blood in an ice slurry for a working day (8·5 h) modify the properties of the plasma? It was shown that haematocrit, plasma ions, metabolites, stress hormones and sex hormones of caudal blood samples were statistically similar when taken from live v. recently sacrificed groups of adult coho salmon Oncorhynchus kisutch. Moreover, this study confirmed by using paired blood samples from cannulated O. kisutch that blood acquired through the caudal puncture technique (mean ±s.e . 142 ± 26 s after capture) was representative of fish prior to capture. Long‐term (8·5 h) cold storage of sockeye salmon Oncorhynchus nerka whole blood caused significant decreases in plasma potassium and chloride, and a significant increase in plasma glucose. Previous research has suggested that these changes largely result from net movements of ions and molecules between the plasma and erythrocytes, movements that can occur within minutes of storage. Thus, blood samples from fishes should be centrifuged as quickly as practicable in the field for separation of plasma and erythrocytes to prevent potentially misleading data.     

Blood-Volume Determination with Evans Blue Dye in Foals

The rate of disappearance of Evans blue dye from the blood after an intravenous injection was studied in young foals, between 4 and 105 days of age. This was found to be age dependant, especially during the first month, the initial dye disappearance being much faster than in the adult horse. This would mean an overestimation of plasma volume, using the single sampling technique, of about 5% during the first day of life, i.e. negligible from a practical point of view considering the standard error of estimation. The effect of exercise on the venous haematocrit was studied, too, in foals less than 3 months of age. There was a significant difference between mean values before and after exercise, and this difference seemed to increase with age, indicating an increasing erythrocytestoring capacity of the spleen. This means that even in young foals, the splenic function should be considered when determining the total blood volume from the plasma volume and the venous haematocrit.     

Treatment of anemia in patients with renal failure using erythropoietin obtained by genetic recombination

In 5 haemodialyzed patients with end-stage renal failure an effect of human recombinant erythropoietin (r-huEpo) on haemoglobin, haematocrit and iron metabolism was studied. After 12 weeks of the treatment, a significant increase in haemoglobin and haematocrit but significant decrease in plasma ferritin were noted. During r-huEpo treatment, one patients presented clinical symptoms of increased blood coagulation whereas another patients an increase in blood pressure. r-huEpo did not influence leukocytes and platelets count as well as liver function tests. Our results suggest, that r-huEpo is highly effective and safe in the treatment of anaemia in patients with chronic uraemia. Iron metabolism, blood pressure and blood coagulation must be monitored during therapy with r-huEpo.     

Plasma insulin concentrations during infusions of potassium and sodium chloride solutions into conscious splenectomized sheep

Haematocrit values, plasma osmolality and the plasma concentrations of sodium, potassium, chloride and insulin were measured in carotid arterial blood before, during and after intravenous infusion of NaCl (0.5 mol 1-1) and KCl (0.5 mol 1-1) at 2 ml min-1 for 105 min into six conscious splenectomized sheep. Hypertonic NaCl infusion was associated with a fall in haematocrit of 1.30 +/- 0.10% (P less than 0.001) and no consistent change in plasma insulin concentration occurred during this infusion. Hypertonic KCl infusion caused the haematocrit to increase by 1.70 +/- 0.39% (P less than 0.001) and the plasma insulin concentration to increase by 60.0 +/- 16.3 mu U ml-1 (P less than 0.01). It was concluded that this increase in insulin concentration was caused by elevation of the plasma potassium concentration and was not due to coincident increases in plasma chloride concentration or osmolality. Shrinkage of the extracellular fluid volume during KCl infusion made no major contribution to the increase in insulin concentration which was probably the result of increased release from the pancreas.     

Seasonal variation in haematological parameters in male and female Tinca tinca

This study was designed to investigate any seasonal (spring, summer, autumn and winter) changes in haematological parameters in the blood of Tinca tinca measuring the number of red blood cells (RBC), haematocrit, white blood cells, and total plasma proteins.The results show significant changes in RBC and haematocrit in males comparing spring and summer with autumn and winter, whereas in females the RBC remained constant for all 4 seasons but the haematocrit decreased in autumn and winter compared to spring and summer. The white blood cells of male and female animals were significantly lower in spring and winter compared to summer and autumn. In male fish total protein contents significantly decreased in autumn and winter compared to spring and summer, whereas in females protein output significantly decreased in winter compared to the other seasons. The results indicate marked seasonal variation in the blood of male and female Tinca tinca. This variation may play a important protective role for the survival of the animals.     

Blood levels of cyclic AMP, thyroxine, uric acid, certain metabolites and electrolytes under heat-stress and dehydration in the pigeon.

The effect of heat stress and dehydration on certain blood parameters were studied in the pigeon. Pigeons exposed to heat-stress and dehydration showed higher haematocrit values. Serum cyclic AMP levels, both with and without corrections made for difference in haematocrit, showed a more than two-fold increase in heat-stressed and dehydrated pigeons. Serum triglyceride level (before and after correction for haematocrit difference) in the experimental birds dropped to less than half that in the control birds. Total serum thyroxine (T4) did not show significant change in the experimentals (either with or without correction for haematocrit), although bound T4 and T3 index showed a statistically significant drop in the experimental group, after the correction for haematocrit. Total serum protein and albumin values after correction for haematocrit difference showed significant decreases in experimental birds. In pigeons exposed to heat-stress and dehydration, serum sodium increased while potassium dropped (with and without haematocrit correction). Heat stress and dehydration did not have any significant effect on serum levels of total cholesterol, uric acid, sodium, potassium, calcium and magnesium.     

Substance P in the blood plasma in hypophysial portal vessels

The aim of the present study was to check if Substance P (SP) is released from the hypothalamus into the hypophysial portal vessels and by this route exerts its direct influence on the adenohypophysis. For this purpose SP radioimmunoactivity was assayed in the blood plasma collected from hypophysial portal vessels and from the cephalic end of the external jugular vein. The SP levels in blood plasma collected from hypophysial portal vessels and from the jugular vein do not differ significantly. Neither does application of a noxious factor, such as bilateral femoral bone fracture, change significantly the SP level in the blood plasma from portal vessels and from the jugular vein. Hypoxia seems to increase the SP level in portal blood plasma and may be followed by its decrease. It is concluded that hypothalamic SP is not released into the hypophysial portal vessels under normal conditions and its direct influence on the adenohypophysis is not mediated this way.     

Blood volume in inbred strain BALB/c, CBA/J and C57BL/10 mice determined by means of 59Fe-labelled red cells and 59Fe bound to transferrin.

Circulating red blood cell (RBC) and plasma volume was determined in male inbred strain BALB/c, CBA/J and C57BL/10 mice by parallel use of the 59Fe-labelled RBC dilution and the dilution of 59Fe bound to transferrin. The whole blood volumes values derived from the venous haematocrit and plasma volume were about double the values calculated from the venous haematocrit and circulating RBC volume. Comparison of the two methods thus explains the marked differences in different studies of blood volume in mice and shows that correct values can be obtained only by parallel measurements of RBC and plasma volume by separate methods, or by correcting the venous haematocrit to whole body haematocrit. Combination of the labelled RBC method and the 59Fe-transferrin method showed the blood volume values in the above strains of mice to be 10.35 +/- 0.16, 7.32 +/- 0.10 and 7.94 +/- 0.15 ml/g b.w. respectively. The ratio of whole body to venous haematocrit in these strains was was 57.3 +/- 1.6%, 68.0 +/- 1.8% and 69.5 +/- 2.2%. Significant interstrain differences were demonstrated in RBC, plasma and blood volume and in the venous and whole body haematocrit and their ratio.     

Haematological effects of stress on a teleost, Esox lucius L.

Stress produces a haemoconcentration, elevated blood lactate, increased glucose concentrations and alters the plasma electrolyte balance in two groups (brackish- and freshwater) of the northern pike, Esox leucius L., after one month's starvation. A method for dorsal aorta catheterization and a receptacle for cannulating fish is described.
The blood glucose level of the freshwater pike was twice that of the brackish-water group, and the plasma sodium and magnesium concentrations in the brackish-water pike were significantly higher. The haematocrit, haemoglobin and blood lactic acid concentrations were higher in freshwater pike. The plasma potassium and calcium concentrations in the two groups did not differ.
Haemoconcentration due to stress by handling for 1.5 min was shown by changes in haematocrit and haemoglobin values. The haemoglobin concentration returned to normal in freshwater pike after 4 h but in brackish-water pike after 12 h.
As a result of handling, the blood lactic acid level rose steeply and required 12 h to return to normal.
The blood glucose concentration rose to its maximum value within 1 h of handling and required two days to return to normal.
The plasma sodium level remained stable after handling, but the potassium level was erratic. In brackish-water, the potassium concentration of the pike remained high for 12 h after stress, but in the freshwater group, after a rise, the concentration fell to below the initial level within 4 h. The changes of the potassium concentrations in relation to sampling time are discussed. The changes in the divalent ion concentrations were marked and similar in the two groups; with an increase lasting 1–4 h and then a fall below the initial level, which was regained after two days.     

Combination of dipeptidylpeptidase IV inhibitor and low dose thiazolidinedione: preclinical efficacy and safety in db/db mice

Thiazolidinediones (TZDs) are currently the most efficacious class of oral antidiabetics. However, they carry the burden of weight gain and haemodilution, which may lead to cardiovascular complications. The present study was designed to ascertain whether a combination of dipeptidyl peptidase IV (DPP IV) inhibitor with low dose of a thiazolidinedione absolves TZD associated weight gain and oedema without compromising its efficacy. In this study, we examined the efficacy and safety of lower dose (1 mg/kg/day) of rosiglitazone, a thiazolidinedione, in combination with 5 mg/kg/day dose of LAF-237 (vildagliptin), a known DPP IV inhibitor, in aged db/db mice after 14 days of treatment and compared the combination with therapeutic dose (10 mg/kg) of rosiglitazone. The combination therapy showed similar efficacy as that of 10 mg/kg/day rosiglitazone in lowering random blood glucose (53.8%, p<0.001 and 54.3%, p<0.001 respectively), AUC ((0-120) min) during oral glucose tolerance test (OGTT) (38.6 %, p<0.01; 38.3%, p<0.01 respectively) and triglyceride levels (63.9% and 61% respectively; p<0.01). Plasma active glucagon like peptide-1 (GLP-1) and insulin levels were found to be elevated significantly (p<0.01 and p<0.05 respectively) in both LAF-237 and combination treated groups following oral glucose load. LAF-237 alone had no effect on random glucose and glucose excursion during OGTT in severely diabetic db/db mice. Interestingly, the combination treatment showed no significant increase in body weight as compared to the robust weight gain by therapeutic dose of rosiglitazone. Rosiglitazone at 10 mg/kg/day showed significant reduction (p<0.05) in haematocrit, RBC count, haemoglobin pointing towards haemodilution associated with increased mRNA expression of Na(+), K(+)-ATPase-alpha and epithelial sodium channel gamma (ENaCgamma) in kidney. The combination therapy escaped these adverse effects. The results suggest that combination of DPP IV inhibitor with low dose of thiazolidinedione can interact synergistically to represent a therapeutic advantage for the clinical treatment of type 2 diabetes without the adverse effects of haemodilution and weight gain associated with thiazolidinediones.