[Serotonin and cardiovascular diseases].
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Biomedical subjects
Publications and source records attributed to R S Reneman.
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Visual inspection of the spectral composition of the Doppler signal as a function of time (sonogram) has been very helpful in detecting the presence of stenoses with substantial lumen narrowing causing abnormal flow patterns. Attempts to grade a stenosis based on the spectral width at peak systole were less successful because of the obscuring effects of the ultrasound beam width with respect to lumen diameter, dimensions of the sample volume, angle of observation, and spectral broadening due to vessel branching and bends. The introduction of color flow imaging has put emphasis on the width of the velocity distribution and the consistency of flow patterns within the region of interest. This technique requires a high resolution in space, velocity, and time necessitating the development of new velocity estimation algorithms. The observed flow patterns can be related to the echogenicity and local wall thickness of peripheral vessels. In addition, the displacement behavior of arterial walls over time provides information about the elasticity of the wall. Knowing the instantaneous velocity of arterial walls, it becomes possible to suppress selectively and adaptively the arterial wall contribution, allowing for the assessment of low blood flow velocities close to the wall and, hence, of wall shear rate. The latter development enables the study of the interaction of blood velocities and the metabolism and structure of the walls, providing possible clues for atherogenesis.
When perfusion pressure is reduced, red blood cell flow in the capillaries of skeletal muscle ceases at a positive pressure difference across the vascular bed, while arterioles dilate and venules are not constricted. This flow cessation (i.e., cessation of red blood cell flow) and luminal diameter changes in capillaries following femoral arterial pressure reduction were investigated in the rabbit tenuissimus muscle in situ (n = 42) using intravital video microscopy. Arterial pressure was reduced by occlusion of the aorta distal to the renal arteries. During the experiments, leg and muscle were placed in a sealed box. The muscle was exposed to low PO2 by leading a gas mixture deprived of O2 through the box. Locally at the muscle surface, i.e., under the microscope objective, PO2 was varied by varying the PO2 in the superfusion solution. In all experiments, the remainder of the muscle was kept at low (< 20 mm Hg) PO2. The incidence of flow cessation was virtually zero at low local (< 20 mm Hg) PO2 and became almost 100% at local values above 70 mm Hg. Initial equivalent capillary diameters were 3.1-5.8 microm (median 4.0 microm) and did not correlate with local O2 tension. During aorta occlusion, capillary diameters significantly (P < 0.0001) decreased by a median value of 8% at all local PO2 values; in 14 out of 54 capillaries local diameter became less than 2.8 microm. The extent of diameter reduction did not correlate with PO2. In the 14 capillaries in which the diameter became less than 2.8 microm flow cessation occurred in only four cases. The minimal diameter reached was always at the site of an endothelial nucleus. The capillary diameter reductions are probably due to passive recoil. In the 48 capillaries in which flow ceased, only in four cases did a red blood cell stop at the site of the nucleus. We conclude that capillary diameter reductions (local and generalized) lead to a considerable increase in capillary resistance which contributes to the occurrence of flow cessation but cannot solely explain it.
Nicorandil (N) and isosorbide dinitrate (ISDN) are vasodilator drugs used in patients with angina. In 24 healthy male volunteers (18-32 years), the acute effect of a single oral dose (20 mg) of N and ISDN on arterial diameter (D), distensibility, and compliance of the elastic common carotid artery (CCA) and the muscular femoral (FA) and brachial (BA) arteries were investigated. The effects on systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and venous hemodynamics were also assessed. In addition, the subacute effects after 8 days of treatment with N (2 x 20 mg/day) and ISDN (3 x 20 mg/day) on these parameters were evaluated. After a 20 mg single oral dose, blood pressure decreased significantly more with ISDN (SBP: 6%; DBP: 14%) than with N (SBP: 2%; DBP: 6%), but after 8 days this decrease in blood pressure was not statistically different between ISDN and N. The diameter of CCA increased more with ISDN (11%) than N (5%) acutely as well as subacutely (ISDN: 12%; N: 9%). Heart rate increased only with ISDN (7% acutely, 3% subacutely). No differences between ISDN and nicorandil were found for acute and subacute effects on SVRI, venous hemodynamics, diameter of muscular arteries (FA, BA), and the distensibility and compliance of elastic (CCA) and muscular (FA, BA) arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Various kinds of abnormal, asynchronous electric activation of the left ventricle (LV) decrease mechanical load in early versus late activated regions of the ventricular wall. Because myocardium usually adapts its mass to changes in workload, we investigated by echocardiography whether regional differences in wall thickness are present in two kinds of asynchronous electric activation of different origin and conduction pathway: epicardial ventricular pacing in dogs and left bundle branch block (LBBB) in patients. In six dogs, 3 months of epicardial LV pacing at physiologic heart rates decreased the thickness of the early activated anterior wall by 20.5 +/- 8.1% without significantly changing LV cavity area and septal thickness. In a retrospective study of 228 LBBB patients, the early activated septum was significantly thinner than the late activated posterior wall. The asymmetry most pronounced was as large as 10% in 28 patients with LBBB and paradoxic septal motion. No difference in regional wall thickness was present in 154 control patients. In conclusion, chronic asynchronous electric activation in the heart induces redistribution of cardiac mass. This redistribution occurs in hearts, which differ in impulse conduction pathway, disease, and species and is characterized by thinning of early versus late activated myocardium.
Ultrasound systems are widely used to visualize in real-time internal structures and blood flow velocity distributions. The latter are estimated from the received ultrasound radio frequency (RF) signals using a mean frequency estimator, capable of estimating the temporal and spatial mean frequency within a given depth and time window (estimation window). Since ultrasound RF-signals are composed of three major signal components (reflections, scattering and noise) it is necessary to suppress the power of the reflections or reverberations (stationary echo removal) to estimate the temporal mean frequency of the signal component induced by scattering originating from red blood cells. However, the stationary echo removal filter in front of the mean frequency estimator will restrict the temporal mean frequency estimation range because the power of the signal component induced by the slowly moving blood is suppressed as well. This article describes a stationary echo removal filter, acting in the RF-domain and adaptive to the temporal mean frequency of the signal component induced by stationary or slowly moving reflections and reverberations. Furthermore, a comparison in performance of this adaptive stationary echo removal filter and several static stationary echo removal filters is presented. For direct comparison of these filter algorithms as far as the effect on the temporal mean frequency estimation range is concerned, the same signal conditions in combination with the same RF-domain mean frequency estimator were used in this comparison. It could be demonstrated that the adaptive echo removal filter, in combination with the RF-domain mean frequency estimator used, exhibits the best performance.
Reflex sympathetic dystrophy (RSD) is a pain syndrome that is characterised by autonomic, motor and sensory disturbances. The syndrome has often been associated with sympathetic dysfunction. Therefore, we investigated whether there are disturbances in the sympathetic function of skin microcirculation in the various clinical stages of RSD. Laser Doppler flowmetry (LDF) was used to obtain information about total (mainly thermoregulatory) skin blood flow (TSBF), since blood flow in arteriovenous anastomoses and subpapillary plexus, which are richly innervated by sympathetic nerve endings, contributes predominantly to the flow signal as obtained by LDF. Capillary microscopy was used to appraise whether the trophic changes, as observed in RSD, result from an impaired nutritive skin blood flow (NSBF). Transcutaneous oximetry (TCPO2) was employed as a measure of the oxygenation of superficial skin layers. Skin temperature (ST) was also determined. Patients were divided into 3 clinical stages: stage I in case of a chronic warmth sensation, stage II in case of an intermittent warmth and cold sensation, and stage III in case of a chronic cold sensation. As compared to controls: (1) TSBF was increased (P < 0.05) at stage I and decreased at stages II (P < 0.05) and III (P < 0.001), (2) NSBF was decreased at stages II (P < 0.05) and III (P < 0.001), (3) TCPO2 was not impaired at any stage, (4) ST was increased (P < 0.01) at stage I and decreased (P < 0.05) at stage III. The present study is the first to report an increase of TSBF at stage I of RSD, which may be caused by a decrease in efferent sympathetic nerve impulses. At stages II and III both TSBF and NSBF were decreased which may reflect increased sensitivity of skin microvessels to (circulating) catecholamines.
Wall shear stress (blood viscosity x wall shear rate), imposed by the flowing blood, and blood pressure are the main mechanical forces acting on a blood vessel wall. Accurate measurement of wall shear stress is important when investigating the development of vascular disease, since both high and low wall shear stresses have been cited as factors leading to vessel wall anomalies. Furthermore, in vitro studies have shown that endothelial cells, which play a key role in the function of the underlying arterial wall, undergo a variety of structural and functional changes in response to imposed shear stress. However, there is practically no knowledge about the influence of wall shear stress on the arterial wall in vivo because of the difficulty in measuring this stress in terms of magnitude and time variation. The method presented in this article to measure the time-dependent wall shear rate in the main arteries is based on the evaluation of velocity profiles determined by means of ultrasound, using off-line signal processing. Pulsed ultrasound is well suited for this application since it is noninvasive. The processing performed in the radio-frequency (RF) domain consists of a mean frequency estimator preceded by an adaptive vessel wall filter. In a pilot study (30 measurements in the carotid artery of five healthy volunteers) we investigated the reproducibility of our method to estimate wall shear rate as compared with the reproducibility of the measurement of blood flow velocity in the middle of the vessel. The coefficient of variation was on the order of 9% for blood flow velocity estimation, and for wall shear rate estimation on the order of 5%.
Skin blood flow in reflex sympathetic dystrophy (RSD) patients has been reported to develop from an increase at an early stage to a decrease at later stages. So far, it remains unclear whether these abnormalities are solely of microcirculatory origin, and result from functional vasospasm or structural vessel wall changes. Eighty-seven RSD patients were categorized as follows: stage I in case of a stationary warmth sensation; stage II in case of an intermittent warmth and cold sensation; and stage III in case of a stationary cold sensation. Laser Doppler flowmetry (LDF) was used as a measure of total skin blood flow and transcutaneous oximetry (TCPO2) as a measure of vascular reactivity in the more superficial skin layers. Local skin heating and reactive hyperaemia were used to study the relative reserve capacity of skin microvessels. Finapres was used to assess digital arterial pressures. As compared to healthy volunteers (n = 16), LDF under control conditions demonstrated an increase in skin blood flow at stage I (P < 0.01). A decrease in skin blood flow under control conditions was seen at stages II (P < 0.05) and III (P < 0.05), but the relative flow reserve capacity, as measured with LDF, was not impaired at these stages. Regression analysis did not show a relation between LDF parameters and duration of the syndrome. TCPO2 revealed no differences between patient groups and controls. Regression analysis did not demonstrate a relation between TCPO2 parameters and duration of the syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
A method is presented to assess in vivo in transparent tissues the leukocyte subtypes that roll in microvessels. In nine rabbits anesthetized with ketamine-xylazine, leukocyte nuclei were stained in situ with acridine yellow (3 mg/kg i.v. for 5 min). Intravital fluorescence video microscopy in 24 mesenteric venules (17-29 microns, median 21) indicated labeling of all rolling leukocytes. On the basis of the shape of their nucleus, 67-100% (median 89) could be classified unequivocally (13-366 cells analyzed, median 77) as polymorphonuclear (PMN, i.e., granulocytes) or monomorphonuclear (lymphocytes and monocytes). Of these classified cells, 94-100% were PMNs (median 100, including 1 stray value of 69%). This PMN percentage was independent of the level of leukocyte rolling (2-36/min, median 14), vessel diameter, flow velocity (0.5-2.5 mm/s), or duration of the experiment (< 6 h). The dye had no significant influence on hemodynamic parameters, systemic leukocyte counts (1.5-7.8 x 10(9)/l), or in vitro differentiation pattern (27-38% granulocytes, 0-2% monocytes, 61-71% lymphocytes). In conclusion, our method demonstrated that the leukocytes that roll in postcapillary venules of the exteriorized rabbit mesentery are almost exclusively granulocytes.
A disadvantage of nonradioactive microsphere techniques is that the processing of samples is time-consuming and complex. We developed and validated a simplified processing method for the fluorescent microsphere (FM) technique. In seven anesthetized dogs with coronary artery stenosis up to six different FM and five different radioactivity labeled microspheres (RM) were injected. Two FM and two RM labels were injected simultaneously to enable inter- and intramethod comparison. After gamma-counting samples of blood, myocardium (n = 168), and other organs (n = 59) were digested in test tubes with 2 N ethanolic KOH (60 degrees C, 48 h), microspheres were sedimented by centrifugation, dye was extracted in the same tube, and fluorescence was measured. With this processing method, recovery of FM was approximately 100%. Good correlations for inter- and intramethod comparisons were found [r = 0.985 +/- 0.01 (mean +/- SD)]. The lower intermethod correlation for blue microspheres (r = 0.958) indicates that the use of this label is less desirable. RM and FM endocardial-to-epicardial blood flow ratios correlated well (r = 0.974). With this one-vessel centrifugal sedimentation method and at least five fluorescently labeled microspheres, blood flow can be reliably measured in various organs, including ischemic myocardium.
Capillary diameter changes were studied in the tenuissimus muscle of 29 urethan-anesthetized New Zealand White rabbits. Capillaries were visualized with transillumination bright-field microscopy (saltwater lens, x 50; resolution approximately 0.3 microns). Median capillary diameter during the control period was 4.4 microns (range 3.2-6.9 microns). Complete aortic occlusion resulted in a reduction of median femoral arterial pressure to 17 mmHg (range 4-22 mmHg). During 2 min of occlusion, capillary diameter decreased by 6%, with greater change on the arteriolar side of the capillary than on the venular side. During reactive hyperemia after release of the occluder, capillary diameter maximally increased by 12% compared with the control period, with a larger response at the arteriolar end of the capillary than at the venular end. Median capillary resistance was estimated to increase by 27% during occlusion and to decrease by 36% during peak reactive hyperemia. The observed diameter changes are compatible with the idea that capillaries change their diameter relative to changes in transmural pressure.
In vitro experiments have shown that the shear stress exerted by flowing blood on the endothelial surface affects the morphology of the vascular wall and the release of vasoactive substances and growth factors by that wall. It is believed that the caliber of a vessel adjusts to the local shear stress to maintain a specific value of the shear stress. The local shear stress follows from local shear rate by multiplying shear rate by the local blood viscosity. The present article describes a method in which ultrasound techniques are used to assess transcutaneously the time-dependent wall shear rate in vivo in arteries. This method is applied to the assessment of wall shear rate in the common carotid artery of volunteers, presumed to be healthy, in two age categories (young age group, 20 to 30 years old, n = 8; old age group, 60 to 70 years old, n = 6). Although the peak shear rate in the young age group is markedly higher than in the old age group, the mean shear rate averaged over a cardiac cycle has the same value of 210 s-1 for both groups, corroborating earlier observations that mean shear rate and, hence, mean shear stress are maintained at a particular value. Conversion of the observed shear rates to shear stresses, assuming a blood viscosity of 3.5 mPa.s for both age groups, gives shear stresses of approximately 0.7 Pa. This is a factor of two lower than the shear stresses estimated from the relation between volume flow and artery caliber (1.5 Pa).
The distensibility of the arterial system, which is partly determined by arterial wall structure, smooth muscle tone, and actual pressure level, decreases with aging and hypertension. Our aim was to compare aortic wall properties in 3- and 6-month-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) at comparable blood pressures in vivo. During ketamine/xylazine anesthesia in rats we performed ultrasound arterial wall tracking and invasive pressure measurements to determine, at the level of the thoracic aorta, diastolic pressure, diastolic lumen area, changes in pressure and lumen area during the cardiac cycle, and indexes of compliance and distensibility. These observations were combined with histological measurements for determination of media cross-sectional area and thickness and the incremental elastic modulus under conditions as expected in situ. Anesthesia abolished the difference in diastolic pressure between SHR and WKY. Between 3 and 6 months of age in WKY, diastolic area and incremental elastic modulus increased significantly, distensibility decreased, and all other recorded variables were not modified. Between 3 and 6 months of age in SHR, diastolic area and incremental elastic modulus increased, distensibility of the aortic wall decreased, and all other mechanical and structural properties did not change significantly. At both ages, diastolic area and compliance were significantly smaller in SHR than WKY. The other mechanical and structural properties measured or calculated at comparable pressure did not differ between strains. Differences between the aorta of 3- and 6-month-old rats and between strains observed in vivo at comparable pressures can largely be attributed to differences in lumen caliber.(ABSTRACT TRUNCATED AT 250 WORDS)
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1. In the present study the relation between regional left ventricular contractile work, regional myocardial blood flow and oxygen uptake was assessed during asynchronous electrical activation. 2. In analogy to the use of the pressure-volume area for the estimation of global oxygen demand, the fibre stress-fibre strain area, as assessed regionally, was used to estimate regional oxygen demand. The more often used relation between the pressure-sarcomere length area and regional oxygen demand was also assessed. 3. Experiments were performed in six anaesthetized dogs with open chests. Regional differences in mechanical work were generated by asynchronous electrical activation of the myocardial wall. The ventricles were paced from the right atrium, the left ventricular free wall, the left ventricular apex or the right ventricular outflow tract. Regional fibre strain was measured at the epicardial anterior left ventricular free wall with a two-dimensional video technique. 4. Regional fibre stress was estimated from left ventricular pressure, the ratio of left ventricular cavity volume to wall volume, and regional deformation. Total mechanical power (TMP) was calculated from the fibre stress-fibre strain area (SSA) and the duration of the cardiac cycle (tcycle) using the equation: TMP = SSA/tcycle. Regional myocardial blood flow was measured with radioactive microspheres. Regional oxygen uptake was estimated from regional myocardial blood flow values and arteriovenous differences in oxygen content. 5. During asynchronous electrical activation, total mechanical power, pressure-sarcomere length area, myocardial blood flow and oxygen uptake were significantly lower in early than in late activated regions (P < 0.05). 6. Within the experiments, the correlation between the pressure-sarcomere length area and regional oxygen uptake was not significantly lower than the one between total mechanical power (TMP) and regional oxygen uptake (VO2,reg). However, variability of this relation between the experiments was less for total mechanical power. Pooling all experimental data revealed: VO2,reg = k1 TMP+k2, with k1 = 4.94 +/- 0.31 mol J-1 k2 = 24.2 +/- 1.9 mmol m-3 s-1 (means +/- standard error of the estimate). 7. This relation is in quantitative agreement with previously reported relations between the pressure-volume area and global oxygen demand. The results indicate that asynchronous electrical activation causes a redistribution of mechanical work and oxygen demand and that regional total mechanical power is a better and more general estimate of regional oxygen demand than the regional pressure-sarcomere length area.
The influence of variations of fiber direction on the distribution of stress and strain in the left ventricular wall was investigated using a finite element model to simulate the mechanics of the left ventricle. The commonly modelled helix fiber angle was defined as the angle between the local circumferential direction and the projection of the fiber path on the plane perpendicular to the local radial direction. In the present study, an additional angle, the transverse fiber angle, was used to model the continuous course of the muscle fibers between the inner and the outer layers of the ventricular wall. This angle was defined as the angle between the circumferential direction and the projection of the fiber path on the plane perpendicular to the local longitudinal direction. First, a reference simulation of left ventricular mechanics during a cardiac cycle was performed, in which the transverse angle was set to zero. Next, we performed two simulations in which the spatial distribution of either the transverse or the helix angle was varied with respect to the reference situation, the spatially averaged variations being about 3 and 14 degrees, respectively. The changes in fiber orientation hardly affected the pressure-volume relation of the ventricle, but significantly affected the spatial distribution of active muscle fiber stress (up to 50% change) and sarcomere length (up to 0.1 micron change). In the basal and apical region of the wall, shear deformation in the circumferential-radial plane was significantly reduced by introduction of a nonzero transverse angle. Thus, the loading of the passive tissue may be reduced by the endocardial-epicardial crossover of the muscle fibers.
Processing of Doppler signals produced by pulsed Doppler systems is based on the assumption that the phase of the received high frequency ultrasound signals changes linearly with depth. However, the random spatial distribution of scatterers is not in accordance with this basic assumption. Consequently, averaging of the demodulated signal over an observation window, covering a few periods of the received signal, does not improve the estimate for the instantaneous quadrature components of the Doppler signal originating from a given depth. Hence, the accuracy of the Doppler velocity estimate is independent of the length of the observation window employed. However, splitting the observation window in subsample volumes, each with a length of one period at the emission frequency, and combining the Doppler signals of the subsample volumes at the last stage of signal processing, i.e., mean Doppler frequency estimation using the autocorrelation technique, results in a considerable reduction of the variance of the velocity estimate. Using a computer simulation of the signal processing involved, it is demonstrated that with subsample volume processing the variance of the velocity estimate attains the same variance as is expected for the RF cross correlation technique.