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Biomedical subjects

R S Reneman

Publications and source records attributed to R S Reneman.

At least 145 records · Page 8Linked to original sources

Influence of platelet-vessel wall interactions on leukocyte rolling in vivo.

The influence of platelet-vessel wall interactions on leukocyte rolling was investigated in rabbit mesenteric venules (diameter, 21-40 microns) using intravital videomicroscopy. Puncture of the wall with glass micropipettes (tip, 6-8 microns) evoked the formation of a thrombus in all venules. In most vessels, emboli were produced as well. The rolling of leukocytes (i.e., their movement along the vessel wall at a velocity clearly lower than that of the other blood cells) was quantitated simultaneously in vessel segments upstream and downstream from a thrombus up to 10 minutes after puncture. During embolization the number of rolling leukocytes decreased significantly from the upstream to the downstream vessel segment (median decrease, 45%; p less than or equal to 0.001). It was still decreased by approximately 50% after embolization had stopped, indicating that the decrease in leukocyte rolling was not caused by inclusion of leukocytes in the emboli. In venules without embolization, leukocyte rolling did not change systematically, indicating that fluid dynamic changes induced by the thrombus do not influence leukocyte rolling. Inhibition of prostaglandin formation with aspirin (100 mg/kg) almost completely abolished the influence of the thromboembolic reaction on leukocyte rolling, but blockade of thromboxane A2 receptors with sulotroban (30 mg/kg) had no effect. In conclusion, this is the first report on a functional interaction in vivo, at a site of vessel wall injury, between platelets, vascular cells, and leukocytes. The findings suggest that substances produced by activated platelets and/or damaged vascular cells diminish leukocyte rolling. The identity of these substances is not yet clear, but the present study indicates that prostaglandins other than thromboxane A2 are involved.

Animals↗

Cardiac and hemodynamic effects of intravenous R80122, a new phosphodiesterase III inhibitor, in a canine model of myocardial ischemia and heart failure.

The cardiac and hemodynamic effects of R80122, a new specific phosphodiesterase III inhibitor, were studied in a closed-chest canine model of acute global left ventricular ischemia complicated by heart failure. The results obtained were compared with those obtained with milrinone. Intravenous infusion of the compounds (0.005 mg/kg/min for both) was started when stable heart failure had developed and was continued for 50 min followed by a washout period of 60 min. Both R80122 and milrinone improved the function of the acutely failing heart, as indicated by the increase in the values of the variables related to left ventricular function, but differences existed. The most striking differences were the normalization of the left ventricular external mechanical efficiency with R80122, but not with milrinone, and the maintenance of aortic blood pressure during infusion of R80122, which decreased during infusion of milrinone. Milrinone tends to induce ventricular tachycardia more frequently than R80122. It can be concluded that R80122 and milrinone improve the function of the acutely failing heart, but that the changes induced by R80122 are better balanced, i.e., enhancement of external mechanical efficiency with maintenance of aortic blood pressure.

Animals↗

New developments in clinical testing of medical devices for Europe 1992.

The unification of Europe is associated with the introduction of many new regulations aiming at, for example, standardization and quality control. Several of these generally normative regulations are pertinent to clinical investigations of medical devices, such as heart valves, pacemakers and cardiac assist devices. Relevant documents dealing with these regulations are the "Guidance for good clinical practice for trials on medicinal products in the European Community," a standard already passed by the European Parliament, and CEN (Comité Européen de Normalisation) document TC258 dealing with "Clinical investigations of medical devices". The latter standard is in discussion among member states of the European Community. In this present survey the most important issues dealt with in these documents will be summarized with emphasis on the aspects relevant to clinical investigations of medical devices.

Equipment and Supplies↗

Assessment of the arterial distension waveform using Doppler signal processing.

AIM: To determine the distension waveform of an artery. METHODS: Ultrasound signals returned by moving structures were processed by pulsed Doppler in order to detect the displacement of the signals with respect to the transducer as a continuous function of time. The results of two sample volumes combined, one located at the anterior and the other at the posterior wall of an artery, yielded the distension waveform of the artery. The distance between the sample volumes in combination with the distension from diastole to systole provided the local distensibility and compliance coefficients. To prevent any part of the structure under observation from moving outside the sample volume, the position of the sample volume was adjusted according to the displacement detected. A disadvantage with this method is that the phase interference of closely spaced structures, i.e. layers of the arterial wall, and the readjustment of the sample volume position may cause artifacts but these can be effectively suppressed by proper processing. CONCLUSIONS: The phase delay between two distension waveforms assessed simultaneously at a known distance can provide the local pulse wave velocity. Subsequently, the Moens-Korteweg relationship, expressing the relationship between pulse wave velocity and the distensibility coefficient, can be used to estimate the distensibility coefficient without measuring the local pulse pressure. The techniques, however, need further evaluation.

Arteries↗

Inhomogeneities in arterial wall properties under normal and pathological conditions.

AIM: To determine whether there are inhomogeneities in arterial wall distensibility with age and hypertension. BACKGROUND: It has been known for some years that arteries lose their elasticity with increasing age and that they are less distensible in subjects with established and borderline hypertension than in age-matched controls. RESULTS OF DATA ANALYSIS: In the carotid artery changes in arterial wall properties are not homogeneously distributed along the bifurcation. Both in older subjects and in those with borderline hypertension the loss of distensibility is most pronounced in the carotid artery bulb, while in borderline hypertensives the proximal part of the bulb, where the baroreceptors are predominantly located, is more affected than other parts of the bulb. The loss of distensibility in the bulb may explain the diminished baroreceptor sensitivity observed in older subjects. The pronounced involvement of the proximal part of the bulb in the decreased distensibility in borderline hypertensives suggests that local stiffening, probably leading to disturbed baroreceptor sensitivity, may contribute to the development of hypertension in these patients. The pattern of inhomogeneities in wall distensibility in borderline hypertensives at a relatively young age (average 38 years) is similar to that seen in older normotensive subjects (average age 57 years), supporting the idea that arteries age faster in hypertensives than in normotensives. CONCLUSION: In management of the borderline hypertensive patient, consideration should be given to preventing early ageing of the arterial wall rather than following arterial blood pressure.

Adult↗

Mapping the sequence of contraction of the canine left ventricle.

A method has been developed to map the sequence of contraction as measured at the epicardial surface of the anterior free wall of the canine left ventricle during sinus rhythm and electrical stimulation of the ventricle. In an area of 35 x 45 mm, 40-60 white markers were attached to the epicardial surface. The motion of the markers was recorded on video and analysed off-line by computer. In an array of 35 regions, regional surface deformation and epicardial fibre strain were calculated from the motion of the markers. Between all adjacent regions, the differences in timing of contraction were determined by cross-correlation of the related fibre strain signals. A map of the time sequence of contraction has been calculated so that the sum of the squares of the deviations between time intervals of the map and the measurements was minimised. If individual correlation coefficients were found to be less than 0.85, the related time difference was discarded from the analysis. If more than 25% of the time differences were discarded because of this reason, the whole map was obtained by determining time of the negative peak of the second time derivative in the early phase of contraction. The accuracy in time marking was sufficient (+/- 7 ms), as compared to the time differences over the epicardial surface, which were found to be on the average between 10 and 80 ms in case of sinus rhythm and electrical stimulation of the right ventricular outflow tract, respectively.

Animals↗

Performance of the isolated, ejecting heart: effects of aortic impedance and exogenous substrates.

The workload of the isolated, left-ventricular ejecting heart (i.e. working heart) is determined by the left atrial filling pressure and the afterload imposed on the left ventricular outflow tract. In addition to the level of end-diastolic aortic pressure, afterload is highly determined by the aortic impedance. For the isolated, ejecting heart optimum matching of the left ventricle to its afterload requires the highest possible similarity between the impedance of the artificial aortic conduit and the natural aortic impedance. The present study shows that the haemodynamic performance of the ejecting rat heart preparation can be affected by the impedance of the aortic conduit. A proper choice of substrates in the perfusion fluid further improves the performance of the heart in the artificial set-up. The present paper also provides guidelines with respect to the design of the aortic cannula and compliance chamber. The occurrence of turbulence, which is related to the Bernoulli pressure drop, is a major determinant of the impedance of the aortic conduit. This effect is used to simulate the natural resistance component of the aortic impedance. Further, the applicability of the perfusion model can be extended by the so-called assisted-mode perfusion, which allows automatic adjustment from antegrade to retrograde perfusion if the heart is not able to generate sufficient pumping power to provide its own coronary perfusion.

Animals↗

Fatty acid accumulation during ischemia and reperfusion: effects of pyruvate and POCA, a carnitine palmitoyltransferase I inhibitor.

The present study was designed to evaluate the effects of POCA, a carnitine palmitoyltransferase I (CPT I) inhibitor, and pyruvate, a substrate inhibiting fatty acid (FA) oxidation, on post-ischemic cardiac FA accumulation on the one hand, and hemodynamic recovery and loss of cellular integrity on the other. To this end isolated, working rat hearts, receiving glucose (11 mM) as substrate, were subjected to 45 min of no-flow ischemia and 30 min of reperfusion. Hearts were perfused with or without POCA (10 microM) and/or pyruvate (5 mM). In the control group the FA content increased significantly during ischemia and remained elevated during reperfusion. Administration of POCA did not affect functional recovery and LDH release significantly, but resulted in about two-fold increased FA levels upon reperfusion as compared to glucose-perfused hearts. Pyruvate markedly improved functional recovery. Addition of this substrate did not affect lactate dehydrogenase (LDH) release, but enhanced FA accumulation during reperfusion. The combined administration of pyruvate and POCA nullified the positive effect of pyruvate on hemodynamic recovery, aggravated LDH release, and further enhanced the accumulation of FAs. The adenine nucleotide content of reperfused hearts was comparable for all groups investigated. In conclusion, during transient ischemia POCA and pyruvate markedly increased cardiac FA accumulation through inhibition of the oxidation of FAs released from endogenous lipid pools. No clear relation was found between the FA content of reperfused hearts and post-ischemic functional recovery.

Adenine Nucleotides↗

Spectral composition of Doppler signals.

The spectral content of the Doppler signal (as revealed by spectral analysis) provides useful diagnostic information about local hemodynamic conditions. Changes in these conditions are used to diagnose atherosclerotic lesions in arteries accessible to ultrasound. Extremely high frequencies, as found in and distal to a tight stenosis, indicate the presence of a jet, while Doppler signals with a wide bandwidth are related to regions with wide velocity ranges and/or disturbed flow patterns. However, the random interactions of the scatterers, the dimensions of the sample volume, the velocity of the scatterers and the method of signal processing used affect the displayed spectral composition of the Doppler signal. This article reviews the basic mechanisms and cautions the investigator against a quick and superficial interpretation of the results obtained without a proper appreciation of the random fluctuations due to the methods used to record and process the signals.

Humans↗

Relation between left ventricular cavity pressure and volume and systolic fiber stress and strain in the wall.

Pumping power as delivered by the heart is generated by the cells in the myocardial wall. In the present model study global left-ventricular pump function as expressed in terms of cavity pressure and volume is related to local wall tissue function as expressed in terms of myocardial fiber stress and strain. On the basis of earlier studies in our laboratory, it may be concluded that in the normal left ventricle muscle fiber stress and strain are homogeneously distributed. So, fiber stress and strain may be approximated by single values, being valid for the whole wall. When assuming rotational symmetry and homogeneity of mechanical load in the wall, the dimensionless ratio of muscle fiber stress (sigma f) to left-ventricular pressure (Plv) appears to depend mainly on the dimensionless ratio of cavity volume (Vlv) to wall volume (Vw) and is quite independent of other geometric parameters. A good (+/- 10%) and simple approximation of this relation is sigma f/Plv = 1 + 3 Vlv/Vw. Natural fiber strain is defined by ef = In (lf/lf,ref), where lf,ref indicates fiber length (lf) in a reference situation. Using the principle of conservation of energy for a change in ef, it holds delta ef = (1/3)delta In (1 + 3Vlv/Vw).

Animals↗

Posturally induced microvascular constriction in patients with different stages of leg ischaemia: effect of local skin heating.

1. Skin microcirculation was investigated in 12 asymptomatic subjects and 76 patients, grouped according to their ankle-to-brachial systolic blood pressure index, in order to evaluate to what extent posturally induced microvascular constriction is dependent on the stage of leg ischaemia at different local skin temperatures. 2. Skin microcirculation was assessed in the supine and sitting position by using laser Doppler fluxmetry at unheated skin temperature and at 36 degrees C, and transcutaneous oximetry at 37 degrees C and 44 degrees C. 3. Skin perfusion and oxygenation diminished with decreasing ankle-to-brachial systolic blood pressure index. In healthy control subjects, perfusion and oxygenation were reduced when changing from the supine to the sitting position, but were enhanced in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure less than 30%), indicating disturbed posturally induced vasoconstriction. 4. Increasing the local skin temperature resulted in a higher perfusion and masked the posturally induced vasoconstriction in healthy subjects. In patients with severe leg ischaemia, however, perfusion was unaltered by the temperature increase, apparently because the microvessels were already maximally dilated. The induction of reactive hyperaemia produced no additional increase in perfusion or oxygenation. 5. It is concluded that posturally induced microvascular constriction in the skin is disturbed in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure index less than 30%). Disturbed microvascular constriction upon dependency was also seen in healthy subjects after local skin heating. This suggests that posturally induced vasoconstriction is mainly regulated by local mechanisms.

Adult↗

Fluid dynamics and the thromboembolic reaction in mesenteric arterioles and venules.

In the mesentery of the anesthetized rabbit, the thromboembolic reaction after wall puncture lasts six times longer in arterioles than in venules, a difference that cannot be explained by fluid dynamic conditions before puncture. In the present study, it was investigated whether this difference in response between arterioles and venules results from a different degree of stenosis by the thrombus and/or a difference in velocity changes resulting in a different pressure drop over the thrombus. Arteriolar and venular mean red blood cell velocity and vessel diameter were measured before puncture and after this injury in the stenosed vessel segment and upstream. Thrombi with similar heights were formed in arterioles and venules and induced similar degrees of stenosis. A surface area reduction less than 55% induced only a small and similar decrease in volume flow (less than 10%) in arterioles and venules. Reduced velocity, a measure of wall shear rate, increased similarly in both vessel types for similar degrees of stenosis. In conclusion, changes in fluid dynamic factors, as induced by thrombus formation, cannot be held responsible for the difference in thromboembolic reaction between arterioles and venules.

Animals↗

An efficient algorithm to remove low frequency Doppler signals in digital Doppler systems.

In color flow imaging, a high flow map rate in combination with a reasonable width of the map and good velocity resolution is essential to properly appreciate the time-dependent phenomena. The velocity resolution depends on the length of the signal segment considered in combination with the settling time of the high pass filter used to eliminate transients and low frequency artifacts. The latter can be reduced by appropriate processing. This paper presents an algorithm to suppress low frequency Doppler signals effectively and efficiently, while all the data points within the segment considered contribute equally to the average Doppler frequency computed. The algorithm is applied to computer generated Doppler signals to evaluate their time and frequency behavior. It is concluded that the proposed scheme functions adequately under various signal conditions.

Algorithms↗

Experimental evaluation of the correlation interpolation technique to measure regional tissue velocity.

A newly developed correlation interpolation method to measure the regional velocity of moving tissue is evaluated in an experimental setup. Pulsed ultrasound echo signals (center frequency 3.5 MHz) are received from a rotating Agar disk containing scattering particles. When averaging over a depth range of 2.2 mm at a pulse repetition frequency (PRF) of 930 Hz, the standard deviation of the measured displacement between 2 successive pulses was found to be +/- 6 microns. In a second series of experiments, the angular velocity of the disk is estimated from the displacement, as measured simultaneously in two different regions located on separate echo lines (PRF = 465 Hz per line). The exact position of both regions in respect to the center of rotation was found to be irrelevant. The accuracy of the calculated angular velocity was found to be better for large angles between the two lines of observation than for small angles.

Agar↗

Use of microphotohemolysis to distinguish differences in erythrocyte treatments.

A new microhemolytic assay was used to determine if this assay could distinguish between normal erythrocytes and those which had been experimentally altered. Solutions of erythrocytes (4% hematocrit in buffer with fluorescein isothiocyanate tagged to 150,000 MW dextran, FITC-DEX) were placed in a hemacytometer and epi-illumination with a Leitz fluorescent microscope was used to activate the fluorochrome. The resultant hemolysis that occurred only in the discrete area of activation was dependent on the total light energy used for activation (45-180 J/cm2). It was quantitated by an analysis of the amount of light transmittance through that area. The presence of glucose in the buffers decreased the rate of hemolysis and increased the time to reach 50% of the maximal response (T50). Erythrocytes treated with diamide had up to a fourfold increase in the rate of hemolysis and a 48% decrease in the T50, while chlorpromazine produced a 51% decrease in the T50 but had no effect on the rate of hemolysis. Gluteraldehyde produced a graded suppression of the hemolysis. These results demonstrate that the microphotohemolytic assay can be used with energy response curves to provide a relatively quick, quantitative determination of altered erythrocytes.

Animals↗

Quantitation of erythrocyte photohemolysis by light microscopy.

In a solution of erythrocytes and a photo-active compound, light activation of the compound produces hemolysis of the cells. This study describes a new assay in which focused light through a microscope is used to induce a circumscribed hemolysis of erythrocytes that have been mixed with fluorescein isothiocyanate-dextran 150,000 (FITC-DEX) and placed in a hemacytometer. The hemolytic response was monitored by detecting transmitted light intensity in the area (1.8 x 10(-4) cm2) of activation. Only cells within the specific microscopic field of activation hemolyze. This allows for multiple sites of activation within one sample. The hemolytic response was dependent on the concentration of FITC-DEX (0.5-4 mg/ml) and on light intensity (53-210 J/cm2) but not on small changes in hematocrit (3%-5%) or on the presence of platelets and leukocytes. Rabbit erythrocytes, however, were almost twice as sensitive as those from guinea pigs. Since the photohemolytic response will depend on the composition and strength of the erythrocyte membrane and presence of oxidant defense mechanisms, we suggest that this assay could be used to detect drug- or disease-induced changes in the red blood cell membrane.

Animals↗

Technical limitations of the present color coded US-Doppler systems in analyzing flow anomalies in arteries.

The pulsatile nature of blood flow, compliance and tapering of arteries, and arterial bifurcations and curves affect the flow distribution within an artery as function of time. Temporarily and spatially secondary flow phenomena may occur. The presence of secondary flow phenomena causes the flow velocity vector to deviate from the axial direction. In general ultrasound Doppler systems only register the velocity component along the line of observation. For color coded Doppler systems the accuracy to assess this velocity component highly depends on the number of subsequent pulses issued along the same line. A high number of repetitive pulses will improve the accuracy, but only at the expense of a reduced frame rate in the Doppler mode, a reduced width of the region of interest, or both. To appreciate properly the time dependent nature of the velocity distribution quite a high frame rate is required. This paper discusses the flow phenomena of interest and the basic factors affecting the accuracy in velocity assessment that can be obtained. Computer generated Doppler signals are analyzed to obtain quantitative information about the standard deviation of the estimate for the velocity in a given sample volume.

Blood Flow Velocity↗