Bo Sandhagen

New guidelines for hemorheological laboratory techniques

This document, supported by both the International Society for Clinical Hemorheology and the European Society for Clinical Hemorheology and Microcirculation, proposes new guidelines for hemorheolog ...

Blood viscosity and peripheral vascular resistance in patients with untreated essential hypertension

Objectives: The viscosity of blood is increased in patients with essential hypertension. The aim of the present study was to investigate the importance of the different variables of blood rheology to total peripheral resistance, and to elucidate whether inappropriate regulation of the formation of erythropoietin could be important. Design: Nineteen consecutive patients with untreated essential hypertension were examined and compared with a group of matched healthy volunteers. Methods: The haemorheologic variables were assessed by rotational viscometry and the haemodynamic variables by bioimpedance cardiography. The serum concentrations of erythropoietin were determined by radioimmunoassay. Results: The whole blood viscosity and peripheral resistance index were elevated in the hypertensive group. The two variables were positively correlated with each other (r=0.68, P=0.0015). The plasma viscosity and erythrocyte aggregation tendency were increased and the erythrocyte deformability, measured as fluidity, was decreased in the hypertensive patients. In the male subpopulation (n=12) the aggregation tendency was positively, and the deformability negatively, correlated with body mass index. The serum concentrations of erythropoietin were equal in the two groups. Conclusions: The increased total peripheral resistance in patients with essential hypertension may in part be explained by an increased blood viscosity, but the possibility of an opposite cause-effect relationship must also be taken into consideration. The haemorheological abnormalities observed in the present patients cannot be explained by high serum levels of erythropoietin.

Impaired erythrocyte fluidity during treatment of renal anaemia with erythropoietin

Abstract. Seventeen haemodialysis patients with renal anaemia were treated with recombinant human erythropoietin (rhEPO) and observed for 30 weeks. The viscosity of whole blood and plasma, the erythrocyte aggregation tendency, and the erythrocyte deformability, measured as fluidity, were analysed every second week. All patients responded with increasing haematocrit and whole‐blood viscosity. The plasma viscosity and the erythrocyte aggregation tendency were already increased before the start of treatment, and remained unchanged during treatment. The basal erythrocyte fluidity tended to be impaired, although not significantly so. During treatment, significant impairment of fluidity was observed at the beginning of the treatment period. After 24 weeks the fluidity started to increase, and it later reached values observed before the start of treatment. Hence, the quality of the erythrocytes formed during the corrective phase of rhEPO treatment differs in some respects from that of cells formed at a normal production rate. The impaired fluidity might have important implications for the flow resistance in small vessels, and contribute to the development or aggravation of hypertension that is often seen during rhEPO treatment.

Anemia associated with advanced prostatic adenocarcinoma : Effects of recombinant human erythropoietin

BACKGROUND AND METHODS. Nine patients with hormone‐refractory metastatic prostatic adenocarcinoma and anemia were treated with recombinant human erythropoietin (rHuEpo) at a median dose of 150 U/kg BW 3 times a week subcutaneously. Baseline hemoglobin (Hb) ranged from 70 to 116 g/L, and the study duration was 12 weeks (median patient participation period was 8 weeks).

Shear stress in the common carotid artery is related to both intima-media thickness and echogenecity The Prospective Investigation of the Vasculature in Uppsala Seniors study

It has previously been shown that the degree of shear stress (SS) in the carotid artery is related to both plaque occurrence and intima-media thickness (IMT). Since the echogenecity also is an important feature of plaques, we investigated if a reduced shear stress also is related to the echolucency of plaque and the intima-media complex. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, left common carotid artery diameter, IMT, the grey scale median (GSM) of the intima-media complex (IM-GSM) and the blood flow velocity were measured by ultrasound. Occurrence of plaque was noted, and the echogenecity of the plaques was visually estimated by the Gray-Weale classification. Shear stress was inversely related to both IMT and IM-GSM (p=0.0084 and p=0.003, respectively), independently of gender and coronary risk, estimated by the Framingham risk score. Shear stress was lower in subjects with carotid plaque (44% of the sample) than in those without (p=0.0013), and was inversely related to the echogenecity in the subjects with plaque (p=0.0092), independently of gender and coronary risk. A low shear stress in the common carotid artery was associated with both a thick IMT and an echolucent intima-media complex. A similar picture was seen when overt plaques were evaluated, suggesting that shear stress is of importance for both the extent and composition of atherosclerosis.

Analysis of Haemorheological Variables—Methodology and Reference Values

Routine methods are proposed for the analysis of haemorheologic variables with only one instrument, a Low Shear 30 rotational couette viscometer. The variables are plasma viscosity, whole blood apparent viscosity, erythrocyte aggregation tendency and erythrocyte fluidity. These variables, in addition to erythrocyte volume fraction, were analysed in a population of 83 healthy hospital staff subjects. The following means and standard deviations were found: Erythrocyte volume fraction, women 42 +/- 3%, men 46 +/- 2%; Plasma viscosity 1.31 +/- 0.07 mPa.s; Whole blood apparent viscosity, women 4.3 +/- 0.4 mPa.s, men 4.8 +/- 0.3 mPa.s; Erythrocyte aggregation tendency 1.00 +/- 0.10; Erythrocyte fluidity 122 +/- 10 Pa-1.s-1.

High ventilatory response to hypoxia in hypertensive patients with sleep apnea.

The ventilatory response to hypoxia (VRH) in relation to daytime arterial blood pressure was studied in 37 patients with the sleep apnea syndrome (SAS). The patients were divided into hypertensives (n = 16) and normotensives (n = 21). The hypertensive group had a significantly higher VRH (ventilatory increase 1.48 1/min BTPS per percent decrease in arterial oxygen saturation) than the normotensive group (0.69 1/min/%, P less than 0.01). The observed difference raises the question whether a high chemoreceptor sensitivity to hypoxaemia can contribute in causing arterial hypertension among cases with SAS.

Whole blood viscosity and erythrocyte deformability are related to endothelium-dependent vasodilation and coronary risk in the elderly. The prospective investigation of the vasculature in Uppsala seniors (PIVUS) study.

It has previously been shown that a high hemoglobin value, a major determinant of whole blood viscosity (WBV), predicts cardiovascular events. One putative mechanism might be an impaired endothelial function. Erythrocyte deformability is another rheologic feature of the erythrocyte being of importance for the flow properties of the blood, especially in the capillaries. The present study evaluates the relationships between blood viscosity, erythrocyte deformability assessed as erythrocyte fluidity (EF), coronary risk and endothelial vasodilatory function. In the population-based PIVUS study (1016 subjects aged 70); endothelium-dependent vasodilation (EDV) was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). WBV, plasma viscosity (PV) and EF were measured in a random sample of 573 subjects. WBV and PV were positively and EF negatively related to Framingham risk score. EDV was inversely related to both whole blood and plasma viscosity. FMD was not related to any rheologic variable. In multiple regression analyses WBV and EF were significantly related to EDV independently of gender, hypertension, smoking, hypercholesterolemia, obesity and diabetes. Acetylcholine-induced vasodilation in the forearm, but not FMD, was negatively related to whole blood viscosity and positively related to EF independently of traditional risk factors in elderly subjects, indicating a pathophysiological link between impaired hemorheology and coronary risk.

Hemorheological and hemodynamic changes in predialysis patients after normalization of hemoglobin with epoetin-alpha.

Objective. Changes in blood viscosity and total peripheral resistance may contribute to increased blood pressure during partial correction of renal anemia with erythropoietin. An increase in hemoglobin level is followed by decreases in cardiac output and left ventricular mass. We examined how normalization of hemoglobin in predialysis patients affects both hemorheological and hemodynamic variables. Material and methods. Twelve moderately anemic predialysis patients (hemoglobin 115.9±7.8 g/l) received epoetin-α with the aim of achieving a normal hemoglobin level (135–160 g/l). Hemorheological variables were measured using rotational viscometry. Cardiac index was determined by means of Doppler echocardiography. Results. After 48 weeks, the hematocrit level had increased from 37.9%±3.0% to 47.0%±3.1% (p<0.0001). Blood viscosity increased from 3.84±0.33 to 4.59±0.4 mPa×s (p<0.001). Blood viscosity standardized to a hematocrit level of 45% and a plasma viscosity of 1.31 mPa×s did not change. Plasma viscosity, erythrocyte aggregation tendency and erythrocyte fluidity remained unchanged. The cardiac index decreased from 2.64±0.57 to 2.19±0.72 l/min/m2 (p<0.05). The total peripheral resistance index increased from 3270±985 to 4013±1046 (dyn×s/cm5)m2 (p<0.05). Blood pressure remained constant, but the amount of antihypertensive medication used increased by 30%. Conclusions. Hemoglobin normalization in predialysis patients raised blood viscosity and total peripheral resistance due to an increase in hematocrit level, without other consistent hemorheological changes. Antihypertensive therapy had to be increased in many patients to maintain an acceptable blood pressure. The cardiac index was reduced, which may have prevented further development of left ventricular hypertrophy.

Transcutaneous CO2 Monitoring in Adults with Sleep-Related Breathing Disorders

The accuracy of transcutaneous CO2 monitoring (PtcCO2) was studied in 22 subjects suspected of having sleep-related breathing disorders, by comparison with arterial CO2 measurements (PaCO2). At rest 40 simultaneous sets of PaCO2 and PtcCO2 were obtained. The mean PaCO2 (+/-SD) was 5.3 +/- 0.9 kPa and PtcCO2 was 5.7 +/- 1.0 kPa (r = 0.79). The ventilatory response to CO2 was evaluated by a CO2 rebreathing method, and simultaneous measurements of PaCO2, PtcCO2 and end-tidal PCO2 (PETCO2) were made every min. Both PaCO2 and PETCO2 increased more during the first min of CO2 rebreathing than PtcCO2 (p less than 0.001). Between 1 to 5 min after the start of rebreathing there were no significant differences between the three methods. During sleep there was an increase in PtcCO2 (by 0.1-0.3 kPa) with each apneic event, the magnitude of the increase depending on the length and distribution of these events. With repeated long apneas there was a cumulative increase in PtcCO2, especially during REM sleep. Continuous PtcCO2 monitoring proved useful in monitoring and diagnosing sleep-related breathing disorders.