On the flow dependency of the electrical conductivity of blood.

Experiments presented in the literature show that the electrical conductivity of flowing blood depends on flow velocity. The aim of this study is to extend the Maxwell-Fricke theory, developed for a dilute suspension of ellipsoidal particles in an electrolyte, to explain this flow dependency of the conductivity of blood for stationary laminar flow in a rigid cylindrical tube. Furthermore, these theoretical results are compared to earlier published measurement results. To develop the theory, we assumed that blood is a Newtonian fluid and that red blood cells can be represented by oblate ellipsoids. If blood flows through a cylindrical tube, shear stresses will deform and align the red blood cells with one of their long axes aligned parallel to the stream lines. The pathway of a low-frequency (< 1 MHz) alternating electrical current will be altered by this orientation and deformation of the red blood cells. Consequently, the electrical conductivity in the flow direction of blood increases. The theoretically predicted flow dependency of the conductivity of blood corresponds well with experimental results. This theoretical study shows that red blood cell orientation and deformation can explain quantitatively the flow dependency of blood conductivity.

Isolated systolic hypertension from a vascular point of view.

Due to the results of antihypertensive intervention studies, isolated systolic hypertension (ISH) has gained new interest lately. Yet, apart from increased aortic stiffness, the specific pathophysiological features of ISH have remained largely undetermined. Therefore, we investigated the elastic properties of the vascular bed of an upper arm segment in uncomplicated ISH patients and matched normotensive controls using an electrical bioimpedance technique. Compared with the controls, the compliance of the arterial bed as a whole at normotensive blood pressure level was on the average 108.0% higher (p < 0.005) in the hypertensive patients. The blood volume of the arterial bed as a whole at operating blood pressure level and that of the larger arteries were significantly higher (40.5%, p < 0.05, and 40.5%, p < 0.01, respectively). The same held true for the venous blood volume (64.4%, p < 0.05), and for the width of the arterial compliance-pressure relation (34.6%, p < 0.01). We concluded that ISH is a separate pathophysiological entity in which all parts of a peripheral vascular bed are changed and the decreased buffering function of the aorta and large arteries is partly compensated for by an increase in small artery compliance.

A mathematical model for the heterogeneity of myocardial perfusion using nitrogen-13-ammonia.

UNLABELLED: Heterogeneity of left ventricular myocardial perfusion is an important clinical characteristic. Different aspects of this heterogeneity were analyzed. METHODS: The coefficient of variation (v), characterizing heterogeneity, was modeled as a function of the number of segments (n), characterizing spatial resolution of the measurement, using two independent pairs of mutually dependent parameters: the first pair describes v as a power function of n, and the second pair adds a correction for n small. n was varied by joining equal numbers of neighboring segments. Local similarity of the perfusion was characterized by the correlation between the perfusions of neighboring segments. Genesis of the perfusion distribution was modeled by repeated asymmetric subdivision of the perfusion into a volume among two equal subvolumes. These analyses were applied to study the differences between 16 syndrome X patients and 16 age- and sex-matched healthy volunteers using 13N-ammonia parametric PET perfusion data with a spatial resolution of 480 segments. RESULTS: The heterogeneity of patients is higher for the whole range of spatial resolutions considered (2 < or = n < or = 480; for n = 480, v = 0.22 +/- 0.03 and 0.18 +/- 0.02; p < 0.005). This is because the first pair of parameters differs between patients and volunteers (p < 0.005), whereas the second pair does not (p > 0.1). For both groups of subjects there is a significant positive local correlation for distances up to 30 segments. This correlation is a formal description of the patchy nature of the perfusion distribution. CONCLUSION: When comparing values of v, these should be based on the same value of n. The model makes it possible to calculate v for all values of n < or = 480. Mean perfusion together with the two pairs of parameters are necessary and sufficient to describe all aspects of the perfusion distribution. For n small, heterogeneity estimation is less reliable. Patients have a higher heterogeneity because their perfusion distribution is more asymmetrical from the third to the seventh generation of subdivision (8 < or = n < or = 128). Therefore, a spatial resolution of n > or = 128 is recommended for parametric imaging of perfusion with PET. Patients have only a very slightly more patchy distribution than volunteers. The differences in perfusion between areas with low perfusion and areas with high perfusion is larger in patients.

Arteriolar constriction in mild-to-moderate essential hypertension: an old concept requiring reconsideration?

OBJECTIVE: To investigate differences between in-vivo properties of a vascular bed in hypertensive patients and normotensive controls. DESIGN: Despite the controversy about the origin of essential hypertension and its accompanying vascular changes, it is generally assumed that the characteristic increase in peripheral resistance when hypertension progresses is caused by arteriolar constriction. Yet, there is little experimental evidence that this assumption generally holds in vivo. METHODS: A non-invasive technique was used for studying properties of the complete vascular bed of an upper arm segment under an occluding cuff in 23 previously untreated hypertensive patients and their matched normotensive controls. The method used the segment's electrical impedance to assess the volumes of extravascular fluid and of arterial and venous blood under varying arterial transmural pressures. RESULTS: Compared with that of matched normotensive controls, the compliance of the large arteries of the vascular bed was on average 50.9% lower (P < 0.001) in the hypertensive patients. The compliance of the complete arterial bed at the operating blood pressure level was also lower (40.0%, P < 0.01), but appeared to be significantly higher (45.9%, P < 0.05) at the normotensive blood pressure level. On the venous side, the patients had a higher blood volume (60.0%, P < 0.01) and an increased myogenic response (68.5%, P < 0.05). CONCLUSIONS: The increase in vascular resistance in the hypertensive patients is due primarily to changes in the large and small vessels of the arterial bed. We found no evidence for a generally increased arteriolar constriction.

Age-related differences in elastic properties of the upper arm vascular bed in healthy adults.

The significance of age-related changes in arterial stiffness has remained largely uncertain in healthy subjects. This appears to be partly due to difficulties in the interpretation of methods for measuring arterial stiffness in vivo. Therefore, a recently developed electrical bioimpedance method was used for studying elastic properties of a vascular bed as a function of age. In 66 healthy subjects, aged 22-82 years, we investigated the vascular bed of an upper arm segment. This vascular bed showed an age-related decrease in the venous blood volume (r = -0.31, p < 0.01) and in the distensibility, the inverse of stiffness, of the larger arteries (r = -0.38, p < 0.001). The distensibility of the arterial bed as a whole at normotensive blood pressure, however, appeared to increase with age (r = 0.32, p < 0.005). The arterial and venous blood volumes, arterial compliance and extravascular fluid volume were significantly higher in the males than in the females. Practically all investigated vascular properties appeared to be related with height, body mass or body mass index. We concluded that comparative studies concerning vascular properties should preferably be performed in subjects matched as to age, gender, height and body mass. In healthy subjects the smaller arteries adjust to the age-related decrease in large artery distensibility by means of an age-related increase in distensibility. These age-related changes in arterial distensibility are caused by changes in the females, and seem to be associated with age-related changes in body mass index rather than with aging per se.

Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure. The Dutch Ibopamine Multicenter Trial Study Group.

OBJECTIVES: We sought to assess the prognostic value of heart rate variability measures, including Poincaré plots, in patients with mild to moderate chronic heart failure. BACKGROUND: Mortality is high in patients with heart failure, and many of them die suddenly. However, identification of high risk patients, particularly those with an increased risk for sudden death, has remained difficult. METHODS: We studied 95 patients with heart failure (mean [+/- SD] age 60 +/- 8 years, left ventricular ejection fraction 0.29 +/- 0.09, New York Heart Association functional class II [81%] and III [19%]) during up to 4 years of follow-up. Heart rate variability measures and Poincaré plots were obtained from 24-h Holter recordings. RESULTS: During follow-up, 17 (18%) of the 95 patients died. In 15 patients, death was cardiac related (11 patients experienced sudden death). None of the conventional time and frequency domain measures of heart rate variability were related to survival. In contrast, abnormal Poincaré plots identified a significantly higher risk for all-cause cardiac death (Cox proportional hazards ratio 5.7, 95% confidence interval [CI] 1.6 to 20.6, univariate analysis) and for sudden cardiac death (hazards ratio 6.8, 95% CI 1.5 to 31.4) compared with those with normal Poincaré plots. Patients with abnormal Poincaré plots were shown to have a lower left ventricular ejection fraction (0.26 +/- 0.10 vs. 0.31 +/- 0.08, p < 0.05) and higher plasma norepinephrine concentrations (506 +/- 207 pg/ml vs. 411 +/- 175 pg/ml, p < 0.05). In multivariate analysis, abnormal Poincaré plots still had independent prognostic value, both for all-cause cardiac mortality and for sudden cardiac death (hazards ratio 5.3, 95% CI 1.2 to 17.1, hazards ratio 4.5, 95% CI 1.0 to 27.5, respectively. CONCLUSIONS: Heart rate variability analysis, as assessed by Poincaré plots, has independent prognostic value in patients with mild to moderate chronic heart failure and identifies an increased risk for all-cause and sudden cardiac death in these patients.

Investigation of the arterial and venous upper arm vascular bed.

Studies concerning vascular changes in hypertension and exercise have shown an increasing need to investigate the properties of a complete vascular bed in vivo. In this study, the repeatability of a non-invasive method for quantifying properties of the vascular bed of an upper arm segment, was investigated in two groups of volunteers (age 22-55 years). One group of subjects (n = 9) were measured twice at a 15 min interval. The other group (n = 8) were measured 4 times with each subject measured daily at the same time. The estimated quantities included the arterial and venous blood volume, the static arterial compliance, the myogenic response of the arm veins and the extravascular fluid volume of the tissue under an occluding cuff at the upper arm. They not only describe properties of the arterial vascular bed as a whole but also of different sized arteries functioning at different intra-arterial pressure. They were derived from the fluid shifts under the occluding cuff that arise when cuff pressure changes, as determined by electrical impedance and blood pressure measurements. The repeatability of the method was well within the physiologically acceptable range and of the same order of magnitude as that of established methods. Established methods however, provide less information about the properties of a vascular bed and result in controversial estimates of the dynamic arterial compliance. Furthermore, the method eliminates the need to match subjects in comparative studies for arterial blood pressure. These features and the sensitivity of the method for (patho)physiological changes, offer the possibility to investigate in vivo many still unknown aspects of the peripheral circulation.

Continuous monitoring of lactate during exercise in humans using subcutaneous and transcutaneous microdialysis.

We have evaluated the possibility of monitoring the plasma lactate concentration in human volunteers during cycle ergometer exercise using subcutaneous and transcutaneous microdialysis. In transcutaneous microdialysis, the relative increase in dialysate lactate concentration exceeded that of plasma lactate concentration by a factor of 6 during exercise due to exercise-induced lactate secretion in sweat. During exercise the subcutaneous microdialysis dialysate lactate concentration underestimated the plasma lactate concentration possibly due to diffusion limitation or adipose tissue lactate production. While it was demonstrated that microdialysis can be used for on-line lactate monitoring, neither subcutaneous nor transcutaneous dialysate lactate concentration were linearly related to the plasma lactate concentration during exercise, and it was found therefore that it was not possible to monitor directly plasma lactate concentration during exercise.

Theory of the determination of systolic time intervals by impedance cardiography.

It is possible to accurately measure the left ventricular ejection time from the dZ/dt signal of impedance cardiography. The pre-ejection period can be measured from simultaneous recordings of ECG and dZ/dt. The thoracic admittance (reciprocal value of thoracic impedance) is the sum of a constant tissue admittance and a varying blood conductance Gb (reciprocal value of the blood resistance). dZ/dt represents the changes in Gb. The notches of the dZ/dt signal, corresponding to opening and closing of the aortic valve, are due to conductivity changes of blood caused by changes in orientation of erythrocytes; near zero-velocity the first derivative with respect to time of these conductivity changes approaches infinity. Therefore, these notches coincide with the actual opening and closing of the valve, although different vessels, including the aorta, contribute to dZ/dt. Comparison of ejection times, simultaneously measured by impedance cardiography and aortic pressure recording, showed excellent agreement for the whole range of measured heart rates (maximum heart rate = 140 beats min-1, n = 70, r = 0.986).

Estimation of blood pressure-related parameters by electrical impedance measurement.

In 13 healthy volunteers a computerized experimental set-up was used to measure the electrical impedance of the upper arm at changing cuff pressure, together with the finger arterial blood pressure in the contralateral arm. On the basis of a model for the admittance response, the arterial blood volume per centimeter length (1.4 +/- 0.3 ml/cm), the venous blood volume as a percentage of the total blood compartment (49.2 +/- 12.6%), and the total arterial compliance as a function of mean arterial transmural pressure were estimated. The effective physiological arterial compliance amounted to 2.0 +/- 1.3 microliters.mmHg-1.cm-1 and the maximum compliance to 33.4 +/- 12.0 microliters.mmHg-1.cm-1. Additionally, the extravascular fluid volume expelled by the occluding cuff (0.3 +/- 0.3 ml/cm) was estimated. These quantities are closely related to patient-dependent sources of an unreliable blood pressure measurement and vary with changes in cardiovascular function, such as those found in hypertension. Traditionally, a combination of several methods is needed to estimate them. Such methods, however, usually neglect the contribution of extravascular factors.

Investigation of the origin of the impedance cardiogram by means of exchange transfusion with stroma free haemoglobin solution in the dog.

PURPOSE OF INVESTIGATION - To determine the contribution of variations in orientation of erythrocytes (orientation effect) to the heart synchronous variations in thoracic impedance in impedance cardiography. DESIGN - The blood of four dogs was gradually replaced by stroma free haemoglobin solution, causing a decrease in resistivity and orientation effect. The decrease in orientation effect was used to determine the contribution of the orientation effect using an extended form of the "parallel conductor" model of the thorax (parallel connection of a tissue admittance Yt and a blood conductance Gb). SUBJECTS - Four adult splenectomised mongrel dogs. MEASUREMENTS and RESULTS - Packed cell volume and resistivity at body temperature of every volume of circulating fluid removed was measured. Real and imaginary parts of the transthoracic impedance and the modulus of the heart synchronous impedance variations were measured just before each exchange. The parallel conductor model was extended to account for the influence on Gb of packed cell volume and orientation of erythrocytes. Applying this extended model, the average variations in Gb at a packed cell volume of 40% were estimated to be 7.46%:3.03% due to volume variations, 4.43% due to orientation effect. After further extending the model to account for the influence of small changes in blood pressure and heart rate, the average volume variations were estimated to range from 2.8% to 3.3% and the average orientation effect from 4.1% to 4.7% at a packed cell volume of 40%. CONCLUSION - Resistivity of the blood is far from constant and the contributions of variations in blood conductivity and volume to the heart synchronous thoracic impedance are of comparable magnitude. The contribution of the volume variations is the sum of the volume variations in the contributing intrathoracic vessels. The effects of variations in orientation are added up in proportion to the relative volumes of the contributing vessels. The extensions of the parallel conductor model brought out all physiological factors determining the heart synchronous thoracic impedance variations: pulse pressures and flows, mean pressures and flows, compliances of all contributing blood vessels, packed cell volume and heart rate, as well as the relevant properties of blood: the relations between volume, flow and orientation effect and the change in orientation effect during decelerating flow.

Electric properties of flowing blood and impedance cardiography.

An effective resistivity is defined for axisymmetric flow through a circular tube with a uniform electric field in the longitudinal direction. The resistivity of flowing blood is found to be a function of the shear rate profile. Under axisymmetric conditions shear rate profiles are a function of a single parameter: the reduced average velocity, which is the average velocity divided by the radius of the tube. The resistivity of human blood was investigated while the blood was in laminar flow in a circular tube with different constant flow rates. The relative change in resistivity in % is given by: -0.45.H.(1 - exp[-0.26.((v)/R)0.39]); where H is the packed cell volume in % and (v)/R is the reduced average velocity in s-1. In accelerating flow the resistivity change is synchronous with the change in flow rate, but in decelerating flow there is an exponential decay characterized by a relaxation time tau. For packed cell volumes of 36.4% and 47.5% tau was estimated to be 0.21 s, for a packed cell volume of 53.7% tau was estimated to be 0.29 s. The resistivity changes in elastic tubes are influenced by both velocity changes and changes in diameter, but in opposite directions.

Investigation of the parallel conductor model of impedance cardiography by means of exchange transfusion with stroma free haemoglobin solution in the dog.

To test one of the assumptions underlying the calculation of stroke volume--namely, that the transthoracic impedance consists of a parallel connection of a tissue impedance and a blood resistance--experiments were carried out on four dogs in which blood was gradually replaced by a stroma free haemoglobin solution, with the purpose of changing the blood resistance while leaving the tissue impedance unchanged. This was accomplished by exchange transfusion in such a way that the volume of the circulating fluid remained constant and the distribution of fluid volume between the fluid compartments was not altered. During the exchange transfusions the mean decrease in resistivity of the circulating fluid was 54%. The packed cell volume and resistivity of every volume of removed circulating fluid were measured. Just before each exchange the real and imaginary parts of the transthoracic impedance were measured. The packed cell volume decreased exponentially with the number of exchanges. This indicates that the circulating fluid volume remained constant during the exchange transfusion. From the packed cell volumes an estimate of the circulating fluid volume was made. Because of the parallel connection all calculations were based on the use of admittance, which is the reciprocal value of impedance. The real and imaginary parts of the transthoracic admittance were calculated from the measured values of the real and imaginary parts of the transthoracic impedance.(ABSTRACT TRUNCATED AT 250 WORDS)

Origin of the impedance cardiogram investigated in the dog by exchange transfusion with a stroma-free haemoglobin solution.

In an anaesthetized dog an exchange transfusion was carried out with stroma-free haemoglobin solution. The total circulating blood volume was kept constant. The heart-syncronous changes in the thoracic electrical impedance (Zo) were measured before and after the exchange transfusion. Zo consists of a parallel connection of a tissue impedance (Zt) and a blood impedance (Zb). With the aid of this model for Zo the relative variations in Zb (delta Zb/Zb) were calculated from the relative variations in Zo (delta Zo/Zo). The marked decrease of delta Zb/Zb during the experiment can only be explained by the fact that apart from the heart-synchronous changes in vascular volume the impedance changes are also caused by flow dependent changes in the electrical conductivity of blood caused by variations in orientation of the erythrocytes.

Observations on blood flow related electrical impedance changes in rigid tubes.

Mammalian blood in pulsatile flow through a rigid tube has been shown to be anisotropic with regard to its electrical conductivity. When flow increases there is a rise in conductivity in the longitudinal and a fall in the radial direction. These changes are caused by flow-dependent variations in the orientation of the disk-shaped erythrocytes.

Outflow from the left and the right coronary artery into the coronary sinus in the dog heart in situ.

The fractions of the left and the right coronary arterial flow determining coronary sinus flow (facs, facd) were measured in the open-chest dog. Both coronary arteries were isolated and perfused at the same pressure, while the sinus outflow was isolated and drained against the prevailing mean pressure in the right atrium. The fractions were determined by injecting 51Cr labeled erythrocytes into each coronary artery selectively and measuring the total resulting radioactivity in the sinus blood. In addition, they were estimated from flow measurements. The values of facs and facd were found to approximate 0.70 and 0.02 respectively. The variability between the different dog hearts was considerable and it was demonstrated that they were not intercomparable with respect to their coronary flow distribution.

Simultaneous perfusion of both coronary arteries and drainage of the coronary sinus in the dog heart in situ.

A technique is described for perfusion of the entire coronary arterial system of the dog heart in situ and for drainage of the coronary sinus blood. Both coronary arteries are cannulated without ligation of major ventricular branches and disconnected from the aorta. The cannulas are connected to an extracorporeal system allowing perfusion under controlled pressure, without ill effects to either the heart or the blood. The arterial perfusion system is fed from the femoral arteries of the dog. The coronary sinus is cannulated for draining the blood to a venous reservoir against a controlled pressure. From the reservoir the blood is pumped into a femoral vein. Thus a preparation is obtained in which the interdependency of coronary circulation and performance of the heart has been discontinued. Under careful monitoring of pressures and flows, and of blood temperature, blood gases and plasma electrolytes, the preparation has been kept in excellent condition for up to 7 hrs.