Blood Volume Expansion Research Articles

Plasma Erythropoietin Levels Are Elevated 24 H Following High Intensity Intermittent Exercise

Blood volume expansion during endurance exercise training is well documented. Factors contributing to a rapid increase in plasma volume during endurance exercise training are well documented, however, the physiological signals involved in stimulating an increase in red cell production are less clear. PURPOSE To examine the change in circulating levels of erythropoietin (EPO) following a high intensity intermittent exercise protocol (EX, 8 bouts of 4 min 85% followed by 5 min at 40%). This exercise protocol is known to induce significant plasma volume expansion within 24 h of exercise. METHODS Blood samples were collected at rest prior to EX and at 30 min, 2 h, and 24 h following EX for determination of EPO levels. 8 active collegeaged subjects (5 men, 3 female) participated in this study. RESULTS 24 hr following EX plasma volume increased 4.5 +/− 0.9 ml/kg or 10.9% (p<0.05) with a 0.11 +/− 0.05 g/kg increase in albumin content (p<0.05). EPO levels at baseline prior to EX averaged 16.5 +/− 2.4 mU/ml and were unchanged immediately following EX averaging 16.8 +/− 2.1 and 15.1 +/− 1.8 mU/ml at 30 and 120 min of recovery. EPO levels increased 37% to 22.5 +/− 4.6 mU/ml 24 h following EX (p<0.05). CONCLUSIONS These data indicate that this high intensity intermittent exercise protocol stimulates a small rise in EPO. It is uncertain if this increase in EPO is sufficient to contribute to the increase in red cell mass during training.

Plasma Erythropoietin Levels Are Elevated 24 H Following High Intensity Intermittent Exercise

Blood volume expansion during endurance exercise training is well documented. Factors contributing to a rapid increase in plasma volume during endurance exercise training are well documented, however, the physiological signals involved in stimulating an increase in red cell production are less clear. PURPOSE To examine the change in circulating levels of erythropoietin (EPO) following a high intensity intermittent exercise protocol (EX, 8 bouts of 4 min 85% followed by 5 min at 40%). This exercise protocol is known to induce significant plasma volume expansion within 24 h of exercise. METHODS Blood samples were collected at rest prior to EX and at 30 min, 2 h, and 24 h following EX for determination of EPO levels. 8 active collegeaged subjects (5 men, 3 female) participated in this study. RESULTS 24 hr following EX plasma volume increased 4.5 +/− 0.9 ml/kg or 10.9% (p<0.05) with a 0.11 +/− 0.05 g/kg increase in albumin content (p<0.05). EPO levels at baseline prior to EX averaged 16.5 +/− 2.4 mU/ml and were unchanged immediately following EX averaging 16.8 +/− 2.1 and 15.1 +/− 1.8 mU/ml at 30 and 120 min of recovery. EPO levels increased 37% to 22.5 +/− 4.6 mU/ml 24 h following EX (p<0.05). CONCLUSIONS These data indicate that this high intensity intermittent exercise protocol stimulates a small rise in EPO. It is uncertain if this increase in EPO is sufficient to contribute to the increase in red cell mass during training.

A role for the paraventricular nucleus of the hypothalamus in the autonomic control of heart and kidney

It is now well accepted that the sympathetic nervous system responds to specific afferent stimuli in a unique non-uniform fashion. The means by which the brain transforms the signals from a single type of receptor into an appropriate differential sympathetic output is discussed in this brief review. The detection of and response to venous filling are used for illustration. An expansion of blood volume has been shown in a number of species to increase heart rate reflexly via sympathetic nerves and this effect is primarily an action of volume receptors at the venous-atrial junctions of the heart. Stimulation of these volume receptors also leads to an inhibition of renal sympathetic nerve activity. Thus the reflex response to an increase in plasma volume consists of a distinctive unique pattern of sympathetic activity to maintain fluid balance. This reflex is dependent on neurones in the paraventricular nucleus (PVN). Neurones in the PVN show early gene activation on stimulation of atrial receptors, and a similar differential pattern of cardiac sympathetic excitation and renal inhibition can be evoked by activating PVN neurones. Cardiac atrial afferents selectively cause a PVN GABA neurone-induced inhibition within the PVN of PVN spinally projecting vasopressin-containing neurones that project to renal sympathetic neurones. A lesion of these spinally projecting neurones abolishes the reflex. With regard to the cardiac sympathetics, there is a population of PVN spinally projecting neurones that selectively increase heart rate by the release of oxytocin, a peptide pathway that has no action on renal sympathetic outflow. In heart failure the atrial reflex becomes blunted, and evidence is emerging that there is a downregulation of nitric oxide synthesis and reduced GABA activity in the PVN. How this might give rise to increased sympathetic activity associated with heart failure is briefly discussed.

Combined influences of mechanical properties and surface roughness on the tribological properties of amorphous carbon coatings

Carbon films (∼2 μm thick) with a range of mechanical properties and underlying substrate roughnesses were evaluated for delamination and wear under conditions of combined impact and sliding contact. One-side-coated and both-sides-coated titanium alloy pin and disk wear couples were assessed using a custom-made impact/sliding pin-on-disk apparatus in a colloid-based blood volume expansion medium. The normal stress distribution along the film/substrate interface upon impact loading by a smooth titanium alloy pin was modelled analytically for each coated system. For disk surface roughness centre-line average ( R a) values below 0.05 μm, the area of disk film delamination was shown to correlate with the presence of tensile stress at the film/substrate interface. The interfacial tensile stress was shown to occur when there was a film/substrate elastic modulus mismatch, either within or outside the perimeter of contact, depending on the direction of the film modulus deviation. We propose that the tensile stress promotes delamination by lifting the film locally from the substrate. With increased disk R a, the area of disk coating loss tended to decrease, because the surface roughness improved the mechanical bonding of the composite system.

Neurochemical brain groups activated after an isotonic blood volume expansion in rats

In order to establish the involvement of particular neurochemical brain groups in the response to blood volume expansion, we analyzed Fos-labeling in combination with immunolabeling for serotonin, tyrosine hydroxylase, vasopressin and oxytocin, 90 min after a sham or i.v. isotonic blood volume expansion (BVE) in unanesthetized, unrestrained rats. We also examined the changes in concentration of oxytocin, atrial natriuretic peptide and vasopressin plasma, induced by blood volume load, to confirm our previous studies. The results demonstrate the participation of specific paraventricular and supraoptic nucleus groups of cells (oxytocinergic-vasopressinergic), serotoninergic dorsal raphé nucleus cells and catecholaminergic A1/A2/A6 groups (in the caudal ventrolateral medulla, nucleus of the solitary tract and locus coeruleus respectively), in the regulatory response to BVE. They provide detailed neuroanatomical evidence to support previous observations showing the contribution of these neurochemical systems in the neural, behavioral and endocrine response to isotonic BVE.

A Randomized Unblinded Pilot Study Comparing Albumin Versus Hydroxyethyl Starch in Spontaneous Bacterial Peritonitis * #

The administration of albumin improves circulatory function, prevents hepatorenal syndrome, and reduces hospital mortality in patients with cirrhosis and spontaneous bacterial peritonitis. This randomized unblinded pilot study compared the effect of albumin (10 patients) and the synthetic plasma expander hydroxyethyl starch 200/0.5 (10 patients) on the systemic hemodynamics of patients with spontaneous bacterial peritonitis. Baseline measurements were performed within 12 hours after diagnosis of infection. Patients then received 2 doses of the volume expander (1.5 g/kg body weight after baseline measurements and 1 g/kg body weight on day 3). Measurements were repeated after infection resolution. Treatment with albumin was associated with a significant increase in arterial pressure and a suppression of plasma renin activity, indicating an improvement in circulatory function. This occurred in the setting of a significant expansion of central blood volume (increase in cardiopulmonary pressures and atrial natriuretic factor) and an increase in systolic volume and systemic vascular resistance. In contrast, no significant changes were observed in these parameters in patients treated with hydroxyethyl starch. Von Willebrand-related antigen plasma levels significantly decreased in patients treated with albumin but not in those treated with hydroxyethyl starch. Serum nitrates and nitrites increased in patients treated with hydroxyethyl starch but not in those treated with albumin. These data suggest an effect of albumin on endothelial function. In conclusion, albumin but not hydroxyethyl starch improves systemic hemodynamics in patients with spontaneous bacterial peritonitis. This effect is due not only to volume expansion but also to an action on the peripheral arterial circulation.

Haemorheology in Exercise and Training

Disruption of the normal rheological properties of blood is considered an independent risk factor for cardiovascular disease and plays a significant role in the aetiology of atherothrombogenesis. The acute increase in whole blood viscosity may unfavourably affect the microcirculatory blood flow and oxygen delivery to the tissues. It is universally accepted that exercise and physical activity performed on a regular basis has health benefits. However, the effects of exercise on the rheological properties of blood have not received much research attention. Recent, limited evidence indicates that the viscosities of whole blood and plasma increase in response to a variety of exercise protocols. The increase in whole blood viscosity is mainly attributed to an increase in haematocrit and plasma viscosity, whereas the deformability and aggregability of red blood cells remain unaltered. The increases in plasma viscosity and haematocrit have been ascribed to exercise-induced haemoconcentration as a result of fluid transfer from the blood to the interstitial spaces. The haemorheological changes associated with strenuous exercise appear to be linked with enhanced oxidative stress and depletion of antioxidant capacity, and that may affect oxygen delivery and availability to the tissues. Although significant advances have been made in many areas of exercise haematology, the long-term effects of endurance training on blood rheology have been very briefly examined and the exact effect of training has not as yet been determined. Available cross-sectional and longitudinal studies indicate that the blood of endurance athletes is more dilute and this has been attributed to an expansion of blood volume, particularly plasma volume as a result of training. The low haematocrit values in trained athletes represent a hydration condition rather than iron stores deficiency. It has been suggested that this hypervolaemia and blood dilutional effect of endurance training may be advantageous for heat dissipation and greater cardiac stroke volume and lower heart rates during exercise. Enhanced blood fluidity also facilitates oxygen delivery to the exercising muscles because of a reduced resistance to blood flow within the microcirculation. Furthermore, the increase in plasma volume may contribute to the body water pool and help offset dehydration. The influence of strength and power training on blood rheology is not known. The physiological mechanisms responsible for and the functional consequences of the haemorheological changes associated with exercise to a large extent remain speculative. The paradox of haematocrit and blood rheology in exercise and training warrants additional studies. Likewise, further investigations are necessary to determine the possible link between overtraining and blood rheological profiles.

Effects of Different Catecholamines on the Dynamics of Volume Expansion of Crystalloid Infusion

The authors studied the influence of alpha, beta, and dopaminergic catecholamines on blood volume expansion in conscious normovolemic sheep before, during, and after a bolus infusion of a crystalloid. A 0.9% NaCl bolus (24 ml/kg in 20 min) was infused in four paired experiments each: no drug, dopamine infusion (50 microg . kg . min), isoproterenol infusion (0.1 microg . kg . min), and phenylephrine infusion (3 microg . kg . min). Blood volume expansion was calculated by the dilution of blood hemoglobin concentration. Dopamine had little effect on peak blood volume expansion (12.7 +/- 0.9 ml/kg) compared with 0.9% NaCl (13.0 +/- 2.7 ml/kg); in contrast, isoproterenol augmented blood volume expansion (18.5 +/- 1.8 ml/kg), and phenylephrine reduced blood volume expansion (8.9 +/- 1.4 ml/kg). Two hours after the 0.9% NaCl bolus, sustained blood volume expansion was greatest in the isoproterenol protocol (12.2 ml/kg), whereas the dopamine protocol (6.8 ml/kg) remained similar to the control protocol (4.1 ml/kg), and the phenylephrine protocol had a net volume loss (-1.9 ml/kg). Some blood volume expansion differences were attributed to changes in renal function as phenylephrine infusion increased urinary output, whereas isoproterenol was associated with antidiuresis. However, dopamine caused diuresis and sustained augmentation of blood volume. Catecholamines can alter the intravascular volume expansion of fluid therapy. beta-Receptor (isoproterenol) stimulation augmented blood volume expansion, whereas alpha (phenylephrine) stimulation reduced blood volume expansion. Combined dopaminergic, beta, and possibly alpha stimulation with dopamine augmented blood volume expansion and cardiac output while inducing diuresis.

This Month in Anesthesiology

This Month in Anesthesiology

Hypertonic versus near isotonic crystalloid for fluid resuscitation in critically ill patients.

Hypertonic solutions are considered to have a greater ability to expand blood volume and thus elevate blood pressure and can be administered as a small volume infusion over a short time period. On the other hand, the use of hypertonic solutions for volume replacement may also have important disadvantages. To determine whether hypertonic crystalloid decreases mortality in patients with hypovolaemia. We searched MEDLINE, EMBASE, The Cochrane Controlled Trials Register and the specialised register of the Cochrane Injuries Group. We checked reference lists of all articles identified and searched the National Research Register. Randomised trials comparing hypertonic to isotonic and near isotonic crystalloid in patients with trauma, burns or undergoing surgery. Two authors independently extracted the data and assessed the quality of the trials. Fourteen trials with a total of 956 participants are included in the meta-analysis. The pooled relative risk (RR) for death in trauma patients was 0.84 (95% confidence interval [CI] 0.69-1.04); in patients with burns 1.49 (95% CI 0.56-3.95); and in patients undergoing surgery 0.51 (95% CI 0.09, 2.73). In the one trial that gave data on disability using the Glasgow outcome scale, the relative risk for a poor outcome was 1.00 (95% CI 0.82, 1.22). This review does not give us enough data to be able to say whether hypertonic crystalloid is better than isotonic and near isotonic crystalloid for the resuscitation of patients with trauma, burns, or those undergoing surgery. However, the confidence intervals are wide and do not exclude clinically significant differences. Further trials which clearly state the type and amount of fluid used and that are large enough to detect a clinically important difference are needed.

Long-term endurance training does not prevent the age-related decrease in left ventricular relaxation properties.

Diastolic filling dynamics in the long-term endurance trained elderly has previously been examined by transmitral flow velocity, which has been shown to be preload dependent. The aim of this study was to assess the effect of long-term endurance training on left ventricular (LV) relaxation in older individuals by using pulsed tissue Doppler imaging. Fourteen master athletes with a history of intensive long-term endurance training, 14 aged-matched sedentary controls and 15 young adult men underwent standard Doppler echocardiography and pulsed Doppler tissue imaging, performed in four-chambers apical view, by placing a sample volume at the level of the mitral annulus. Stroke volume was significantly higher and heart rate lower in master athletes compared with aged-matched sedentary subjects. Transmitral Peak E velocity and ratio E/A were significantly higher in master athletes, but did not reach the values of young men. Peak LV wall motion during the early filling phase, an index of LV relaxation, were significantly higher in young men than in both groups of older individuals. However, similar values were obtained between master athletes and sedentary counterparts. Our data provide evidence that long-term training does not reduce the age-related decline in LV relaxation properties in humans. This finding implies that other mechanisms, such as increased LV filling pressures due to expanded blood volume, are probably responsible for the higher contribution of early diastolic filling to LV filling in master athletes compared with their sedentary counterparts. However this hypothesis needs to be confirmed.

Risques potentiels du remplissage vasculaire

Blood volume expansion is the main treatment of hypovolemia, but may induce adverse effects. The risks of adverse effects are all the more high since the pre-load reserve of the patient is low. Adverse effects may be linked to the specific effects of the infused solutions, or directly induced by fluid loading. These latter complications may be due to the increase in hydrostatic pressure, an interstitial or a cellular edema, an induced hypothermia, or metabolic disturbances.

Paramètres dynamiques non invasifs prédictifs de l'efficacité d'un remplissage vasculaire

Circulatory failure treatment needs to assess blood volume status, in order to detect a hypovolemia requiring blood volume expansion. Unfortunately, significant fluid responsiveness occurs in only 40–70% of critical care patients after blood volume expansion, suggesting the inability of central venous pressure, pulmonary wedge pressure or conventional echocardiographic parameters to detect hypovolemia and to predict fluid responsiveness. In this way, new dynamic echocardiographic parameters have recently been proposed in mechanically ventilated patients, using the heart lung interactions, such as respiratory changes of aortic blood flow velocity, and of diameters of superior and inferior vena cava. Echocardiography Doppler allows now to completely investigate hemodynamic status in critical care patients.

Critères clinicobiologiques prédictifs de l'efficacité du remplissage vasculaire

The clinical situation may be a major decision-making factor to indicate blood volume expansion (VE). When associated with the measurement of induced changes in systolic ejection volume or cardiac output, the hemodynamic effect of a ”fluid challenge” allows to discriminate between responders and non responders of VE. In the critically ill patient, the effect of passive leg raising on arterial pulse pressure has a good predictive value of VE response. Functional renal dysfunction and hyperlactatemia are the main biological features observed in hypovolemia but lack of specificity. As shown by the clinical studies done in patients with acute circulatory failure, the proportion of responders ranges between 40% and 72%, when VE is indicated according to these clinical and biological criteria.

Critères de jugement de l'efficacité du remplissage vasculaire [champ 5

Numerous criteria may be used to assess fluid responsiveness. Measurements of ejection volume, cardiac output or oxygen transport are direct indicators of the efficacy of blood volume expansion (VE). Indirect criteria (ventilation induced changes in arterial pressure or pulse pressure, oxygen consumption, lactate, splanchnic perfusion, microcirculation) may reflect the efficacy of VE but they lack of specificity.

Les critères hémodynamiques statiques prédictifs de l'efficacité d'un remplissage vasculaire

Numerous static hemodynamic criteria are used to measure cardiac preload and predict the efficacy of blood volume expansion (VE): right and left filling pressures (central venous and pulmonary wedge pressure), ventricular end-diastolic volume and areas, total blood or intra-thoracic volume, ejection time indexes as measured by esophageal doppler ultrasound. Due to different technical and physiological limitations, these static criteria are not good predictors of the response to VE.

Critères de mauvaise tolérance et d'arrêt du remplissage vasculaire [champ 6

During fluid loading, the increase or the occurrence of a cerebral edema, a pulmonary edema or a right ventricle dilatation may indicate the cessation of blood volume expansion (VE). In critically ill neurologic patients, the effect of VE must be monitored on cerebral perfusion pressure. An induced pulmonary edema or hypoxemia are good indicators of VE cessation in patients breathing spontaneously, but these criteria are less accurate under mechanical ventilation. During circulatory failure and shock, the tolerance of VE may be assessed by Doppler echocardiography to detect an acute right ventricular dilatation or a paradoxical septum motion.

Cardiac Enlargement in a Mouse Model of Intestinal Cancer

1233 Cancer-induced cachexia is a life-threatening wasting syndrome characterized by reduced body mass and decreased antioxidant defense systems. This condition is often associated with the activation of the immune system and also heart failure. PURPOSE: To characterize cardiac muscle remodeling in a cachexic mouse model induced by intestinal tumors. The APC+/− mouse used in this study has a high incidence of intestinal tumor formation. We hypothesized that these cachexic mice would have altered heart remodeling. METHODS: Female C57BL6 (CON, n = 7) and APCmin+/− (MIN, n = 7) mice, 6–8 months of age, were monitored for daily food intake. Animals were sacrificed and liver, heart, and tibias were excised. Liver catalase (CAT) activity was measured spectrophotometrically. Cardiac α-myosin heavy chain and 18S mRNA abundance were analyzed by RT-PCR. RESULTS: CON and MIN ate similarly (p>0.05), but MIN BW was decreased by 20.5% (p<0.05). MIN CAT was decreased 54% compared to CON. The heart weight:tibia length ratio was significantly increased 27% in MIN compared to CON (p<0.05). Cardiac α-myosin heavy chain, corrected with 18S and normalized to CON was decreased 40% in MIN (p = 0.045). CONCLUSIONS: Cachexic female APCmin+/− mice, as described by decreased body weight with normal eating behavior as well as decreased catalase activity, suffer from cardiac hypertrophy with altered remodeling. While the stimulus of cardiac enlargement in this cachexic model is not certain, blood volume expansion and atrial natriuretic peptide signaling may be important mechanisms for the induction of this cardiac enlargement. This study was funded by the Colorectal Cancer COBRE program from the National Institute of Health/USC.

Cardiac Enlargement in a Mouse Model of Intestinal Cancer

1233 Cancer-induced cachexia is a life-threatening wasting syndrome characterized by reduced body mass and decreased antioxidant defense systems. This condition is often associated with the activation of the immune system and also heart failure. PURPOSE: To characterize cardiac muscle remodeling in a cachexic mouse model induced by intestinal tumors. The APC+/− mouse used in this study has a high incidence of intestinal tumor formation. We hypothesized that these cachexic mice would have altered heart remodeling. METHODS: Female C57BL6 (CON, n = 7) and APCmin+/− (MIN, n = 7) mice, 6–8 months of age, were monitored for daily food intake. Animals were sacrificed and liver, heart, and tibias were excised. Liver catalase (CAT) activity was measured spectrophotometrically. Cardiac α-myosin heavy chain and 18S mRNA abundance were analyzed by RT-PCR. RESULTS: CON and MIN ate similarly (p>0.05), but MIN BW was decreased by 20.5% (p<0.05). MIN CAT was decreased 54% compared to CON. The heart weight:tibia length ratio was significantly increased 27% in MIN compared to CON (p<0.05). Cardiac α-myosin heavy chain, corrected with 18S and normalized to CON was decreased 40% in MIN (p = 0.045). CONCLUSIONS: Cachexic female APCmin+/− mice, as described by decreased body weight with normal eating behavior as well as decreased catalase activity, suffer from cardiac hypertrophy with altered remodeling. While the stimulus of cardiac enlargement in this cachexic model is not certain, blood volume expansion and atrial natriuretic peptide signaling may be important mechanisms for the induction of this cardiac enlargement. This study was funded by the Colorectal Cancer COBRE program from the National Institute of Health/USC.

Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients

To evaluate the extent to which respiratory changes in inferior vena cava (IVC) diameter can be used to predict fluid responsiveness. Prospective clinical study. Hospital intensive care unit. Twenty-three patients with acute circulatory failure related to sepsis and mechanically ventilated because of an acute lung injury. Inferior vena cava diameter (D) at end-expiration (Dmin) and at end-inspiration (Dmax) was measured by echocardiography using a subcostal approach. The distensibility index of the IVC (dIVC) was calculated as the ratio of Dmax - Dmin / Dmin, and expressed as a percentage. The Doppler technique was applied in the pulmonary artery trunk to determine cardiac index (CI). Measurements were performed at baseline and after a 7 ml/kg volume expansion using a plasma expander. Patients were separated into responders (increase in CI > or =15%) and non-responders (increase in CI <15%). Using a threshold dIVC of 18%, responders and non-responders were discriminated with 90% sensitivity and 90% specificity. A strong relation (r = 0.9) was observed between dIVC at baseline and the CI increase following blood volume expansion. Baseline central venous pressure did not accurately predict fluid responsiveness. Our study suggests that respiratory change in IVC diameter is an accurate predictor of fluid responsiveness in septic patients.