The volume-dependency of parallel conductance throughout the cardiac cycle and its consequence for volume estimation of the left ventricle in patients.

OBJECTIVE: To study the hypothesis that the electrical conductance of tissues and fluids (parallel conductance (G(p))) around the ventricle depends on left ventricular volume throughout the cardiac cycle. METHODS: We extended a recently developed method to determine G(p) throughout the cardiac cycle. First, we compared the estimates of parallel conductances obtained with the new method (G(a)(p)) with those of the conventional one (G(1)(p)), both averaged over the cardiac cycles. Secondly, G(a)(p) was determined throughout the cardiac cycle and its volume dependency was assessed. Thirdly, the factor alpha was calculated as the ratio between stroke volume, obtained by the conductance method using G(1)(p), and that obtained by a thermodilution method. Because the non-homogeneous field was indicated to be the reason for the dependency of G(p) on left ventricular volume as well as for the need for alpha, we tested whether the hypothesis implies that a correction with alpha is not needed if G(p) is determined throughout the cardiac cycle. RESULTS: We found a negative linear relation between G(p) and left ventricular volume. This relation appeared to be reproducible within each patient. Furthermore, we found that alpha deviates from 1 primarily due to the dependency of G(p) on left ventricular volume. CONCLUSION: To obtain stroke volume or to determine absolute left ventricular volume continuously within a cardiac cycle, G(p) should be determined throughout each cardiac cycle and if a constant G(p) throughout the cardiac cycle is used a correction with the factor alpha should be made to correct for a possible influence of electrical field heterogeneity.

Assessment of the spatial homogeneity of artery dimension parameters with high frame rate 2-D B-mode.

To elicit vessel wall inhomogeneities in diameter and distension along an arterial segment, a 2-D vessel wall-tracking system based on fast B-mode has been developed. The frame rate of a 7.5-MHz linear-array transducer (length 36 mm) is enhanced by increasing the pulse-repetition frequency to 10 kHz, decreasing the number of echo lines per frame from 128 to 64, or increasing the interspacing between echo lines with a factor of two or four. Dedicated software has been developed to extract for each echo-line the end-diastolic diameter from the B-mode image and the 2-D distension waveform from the underlying radiofrequency (RF) information. The method is validated in tubes with various focal lesion sizes. Straight segments of presumably homogeneous common carotid arteries have also been tested. The temporal and spatial SD of diameter or distension reveals inhomogeneities in time or space (i.e., inhomogeneities in artery characteristics). The method can be implemented in echo systems supporting high frame rates and real-time processing of radiofrequency data.

Assessment of local pulse wave velocity in arteries using 2D distension waveforms.

The reciprocal of the arterial pulse wave velocity contains crucial information about the mechanical characteristics of the arterial wall but is difficult to assess noninvasively in vivo. In this paper, a new method to assess local pulse wave velocity (PWV) is presented. To this end, multiple adjacent distension waveforms are determined simultaneously along a short arterial segment, using a single 2D-vessel wall tracking system with a high frame rate (651 Hz). Each B-mode image consists of 16 echo lines spanning a total width of 15.86 mm. Dedicated software has been developed to extract the end-diastolic diameter from the B-mode image and the distension waveforms from the underlying radiofrequency (rf) information for each echo-line. The PWV is obtained by determining the ratio of the temporal and spatial gradient of adjacent distension velocity waveforms. The proposed method is verified in a phantom and in the common carotid artery (CCA) of humans. Phantom experiments show a high concordance between the PWV obtained from 2D distension velocity waveforms (4.21 +/- 0.02 m/s) and the PWV determined using two pressure catheters (4.26 +/- 0.02 m/s). Assuming linear spatial gradients, the PWV can also be obtained in vivo for CCA and averages to 5.5 +/- 1.5 m/s (intersubject variation, n = 23), which compares well to values found in literature. Furthermore, intrasubject PWV compares well with those calculated using the Bramwell-Hill equation. It can be concluded that the PWV can be obtained from the spatial and temporal gradient if the spatial gradient is linear over the observed length of the artery, i.e. the artery should be homogenous in diameter and distension and the influence of reflections must be small.

A new approach to determine parallel conductance for left ventricular volume measurements.

OBJECTIVES: To determine absolute ventricular volume with the conductance catheter technique, the electrical conductance of tissues and fluids (parallel conductance) around the ventricle should be determined precisely. METHODS: A new objective method to estimate parallel conductance based on analysis of the dilution curve of hypertonic saline was investigated. The parallel conductances obtained with the new method (G(a)(p)) were compared to those obtained with the conventional method (G(l)(p)). The study was performed in the left ventricle of 12 patients. RESULTS: G(a)(p) was not significantly different from G(l)(p). For the G(l)(p) method the average percentage difference between duplicate values, both taken as absolute values, was 15.06% and for the G(a)(p) method it was 4. 01%. Thus the reproducibility of the method is a factor four better than that of the method. This difference appeared to be significant. CONCLUSION: We conclude that a smaller number of injections will be required to obtain the same precision using our method.

Mean wall shear stress in the femoral arterial bifurcation is low and independent of age at rest.

In elastic arteries, mean wall shear stress appears to be close to 1. 5 Pa, the value predicted by the theory of minimal energy loss. This finding in elastic arteries does not necessarily represent the situation in muscular arteries. Elastic arteries have to store potential energy, while muscular arteries have mainly a conductive function. Therefore, we determined wall shear stress and its age dependency in the common and superficial femoral arteries, 2-3 cm from the flow divider in 54 presumed healthy volunteers between 21 and 74 years of age, using a non-invasive ultrasound system. Prior to the study, the reliability of this system was determined in terms of intrasubject variation. Mean wall shear stress was significantly lower in the common femoral artery (0.35 +/- 0.18 Pa) than in the superficial femoral artery (0.49 +/- 0.15 Pa). In all age categories, peak systolic wall shear stress and the maximal cyclic change in wall shear stress were not significantly different in the common and the superficial femoral arteries. Peak systolic wall shear stress in the common and the superficial femoral arteries was not significantly different from the value previously determined in the common carotid artery, but mean wall shear stress was lower in the common and superficial femoral arteries than in the common carotid artery by a factor of 2-4. In both the common and the superficial femoral arteries, mean, peak systolic and maximal cyclic change in wall shear stress did not change significantly with age, nor did diameter. We conclude that, as compared to elastic arteries, mean wall shear stress is low in the conductive arteries of a resting leg, due to backflow during the first part of the diastolic phase of the cardiac cycle and the absence of flow during the rest of the diastolic phase. Mean wall shear stress is lower in the common than in the superficial femoral artery due to additional reflections from the deep femoral artery.

In the femoral artery bifurcation, differences in mean wall shear stress within subjects are associated with different intima-media thicknesses.

In elastic arteries, intima-media thickening is more pronounced in areas with low than with high mean and peak wall shear stress. These findings in elastic arteries are not necessarily representative of the situation in muscular arteries. The former arteries have to store volume energy, whereas the latter are mainly conductive vessels. It was the aim of the present study to investigate noninvasively whether differences in wall shear stress within a muscular artery bifurcation, if any, were associated with different intima-media thicknesses (IMTs). The effect of age on the possible differences was assessed as well. We determined IMT and mean, peak systolic, and the maximum cyclic change in shear stress near the posterior wall in the common (FC) and the superficial (FS) femoral artery 20 to 30 mm from the flow divider in 54 presumed healthy subjects between 21 and 74 years of age. Results were considered in terms of intrasubject differences. Before the study, the reliability of the ultrasonic system to assess wall shear rate and IMT was determined in terms of intrasubject variability. IMT at the posterior wall was significantly larger in the FC than in the FS, probably owing to the significantly lower mean wall shear stress at this site in the FC. The relative differences in IMT and mean wall shear stress between FC and FS were independent of age. The difference in wall shear stress between both arteries can likely be explained by a different influence of reflections. In both the FC and FS, mean, peak systolic, and maximum cyclic change in shear stress near the posterior wall did not change significantly with age, whereas IMT did increase significantly with age.

Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16.

We have performed linkage analysis on 21 families with pseudoxanthoma elasticum (PXE) using 10 polymorphic markers located on chromosome 16p13.1. The gene responsible for the PXE phenotype was localized to an 8-cM region of 16p13.1 between markers D16S500 and D16S3041 with a maximum lod score of 8.1 at a recombination fraction of 0.04 for marker D16S3017. The lack of any locus heterogeneity suggests that the major predisposing allele for the PXE phenotype is located in this region. Haplotype studies of a total of 36 PXE families identified several recombinations that further confined the PXE gene to a region (< 1 cM) between markers D16S3060 and D16S79. This PXE locus was identified within a single YAC clone and several overlapping BAC recombinants. From sequence analysis of these BAC recombinants, it is clear that the distance between markers D16S3060 and D16S79 is about 820 kb and contains a total of nine genes including three pseudogenes. We predict that mutations in one of the expressed genes in the locus will be responsible for the PXE phenotype in these families.

Conductance method for the measurement of cross-sectional areas of the aorta.

A modified conductance method to determine the cross-sectional areas (CSAs) of arteries in piglets was evaluated in vivo. The method utilized a conductance catheter having four electrodes. Between the outer electrodes an alternating current was applied and between the inner electrodes the induced voltage difference was measured and converted into a conductance. CSA was determined from measured conductance minus parallel conductance, which is the conductance of the tissues surrounding the vessel times the length between the measuring electrodes of the conductance catheter divided by the conductivity of blood. The parallel conductance was determined by injecting hypertonic saline to change blood conductivity. The conductivity of blood was calculated from temperature and hematocrit and corrected for maximal deformation and changes in orientation of the erythrocytes under shear stress conditions. The equations to calculate the conductivity of blood were obtained from in vitro experiments. In vivo average aortic CSAs. determined with the conductance method CSA(G) in five piglets, were compared to those determined with the intravascular ultrasound method CSA(IVUS). The regression equation between both values was CSA(G)=-0.09+1.00 x CSA(IVUS), r=0.97, n=53. The mean difference between the values was -0.29%+/-5.57% (2 standard deviations). We conclude that the modified conductance method is a reliable technique to estimate the average cross-sectional areas of the aorta in piglets.

Differences in near-wall shear rate in the carotid artery within subjects are associated with different intima-media thicknesses.

In the common carotid artery, reflections originating from the periphery and the flow divider may affect the shape of the flow velocity profile and, hence, near-wall shear rate (WSR) differently just before the bifurcation (location B) than 20 to 30 mm farther upstream (location A). Recent developments in ultrasound technology allow the assessment of WSR and intima-media thickness (IMT) at the same site in the carotid artery in vivo. We therefore determined WSR at locations A and B and investigated whether the differences between both sites, if any, were associated with different IMTs and different mechanical properties of the arterial wall. The effect of age on the possible differences was assessed as well. The study was performed on presumably healthy volunteers (n=53). In all individuals, IMT was larger at location B than at location A. The relative difference in IMT between both locations was not affected by age. No significant differences in diameter and distension were found between locations. Near peak systolic and near mean WSR at the posterior wall (PWSRp and MWSRp, respectively) were significantly lower at location B than at location A. The relative differences in PWSRp and MWSRp between both locations within subjects were independent of age. The velocity profiles were more blunted at location A than at location B. PWSRp and MWSRp significantly decreased and IMT significantly increased with age at both locations. IMT was negatively correlated with PWSRP and MWSRP at location B, but this correlation was not significant at location A. In summary, in the common carotid artery, the lower WSR near the bifurcation, as compared with 20 to 30 mm upstream, is associated with a larger IMT than at the more proximal site. The relative difference between both locations within subjects is independent of age.

The compliance of the porcine pulmonary artery depends on pressure and heart rate.

1. The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd) and pseudo-static compliance (Cps) of the pulmonary artery was studied at a constant and a changing heart rate. Cd is the change in cross-sectional area (CSA) relative to the change in Ppa throughout a heart cycle. Cps is the change in mean CSA relative to the change in mean Ppa. If Cd is known, pulmonary blood flow can be computed from the Ppa using a windkessel model. We investigated whether Cps can be interchanged with Cd. 2. In nine anaesthetized pigs, we determined the mean CSA and Cd of the pulmonary artery at various Ppa levels, ranging from approximately 30 to 10 mmHg, established by bleeding. Two series of measurements were carried out, one series at a spontaneously changing heart rate (n = 9) and one series at a constant heart rate (n = 6). To determine CSA a conductance method was used. 3. Cps depended on pressure. The mean CSA versus mean Ppa curves were sigmoid and steepest in the series with the increasing heart rate (established by bleeding). The CSA versus Ppa loop during a heart cycle, giving Cd, was approximately linear and almost closed. The Cd versus mean Ppa relationship was bell shaped. Its width was smaller if the heart rate increased during the series of measurements. The pressure, where Cd was maximum, was higher at higher heart rates. Furthermore, the maximum Cd was not affected by the heart rate. 4. Because the pulmonary artery constricts with increasing heart rate, Cps will be overestimated during procedures where heart rate increases. Cd should be determined on a beat-to-beat basis to calculate flow because it changes with mean pulmonary arterial pressure and heart rate.

Determination of the mean cross-sectional area of the thoracic aorta using a double indicator dilution technique.

A double indicator dilution technique for determining the mean cross-sectional area (CSA) of a blood vessel in vivo is presented. Analogous to the thermodilution method, dilution of hypertonic saline was measured by an electrical conductance technique. Because the change in conductance rather than absolute conductance was used to calculate CSA, pulsatile changes in shear rate of blood and conductance of surrounding tissues had no effect on the data. To calculate CSA from an ion mass balance, cardiac output was needed and estimated from the thermodilution curve using the same "cold" (hypertonic) saline injection. The mean CSA, obtained from this double indicator dilution method (CSAGD), was compared with the CSA obtained from the intravascular ultrasound method (IVUS) in 44 paired observations in six piglets. The regression line is close to the line of identity (CSAGD = -1.83 + 1.06 . CSAIVUS, r = 0.96). The difference between both CSAs was independent of the diameter of the vessel, on average -0.99 mm2 +/- 2.64 mm2 (mean CSAGD = 46.84 +/- 8.21 mm2, mean CSAIVUS = 47.82 +/- 9.08 mm2) and not significant. The results show that the double indicator dilution method is a reliable technique for estimating the CSA of blood vessels in vivo.

Single injection thermodilution. A flow-corrected method.

BACKGROUND: Application of the Stewart-Hamilton equation in the thermodilution technique requires flow to be constant. In patients in whom ventilation of the lungs is controlled, flow modulations may occur leading to large errors in the estimation of mean cardiac output. METHODS: To eliminate these errors, a modified equation was developed. The resulting flow-corrected equation needs an additional measure of the relative changes of blood flow during the period of the dilution curve. Relative flow was computed from the pulmonary artery pressure with use of the pulse contour method. Measurements were obtained in 16 patients undergoing elective coronary artery bypass surgery. In 11 patients (group A), pulmonary artery pressure was measured with a catheter tip transducer, in a partially overlapping group of 11 patients (group B), it was measured with a fluid-filled system. For reference cardiac output we used the proven method of four uncorrected thermodilution estimates equally spread over the ventilatory cycle. RESULTS: A total of 208 cardiac output estimates was obtained in group A, and 228 in group B. In group B, 48 estimates could not be corrected because of insufficient pulmonary artery pressure waveform quality from the fluid-filled system. Individual uncorrected Stewart-Hamilton estimates showed a large variability with respect to their mean. In group A, mean cardiac output was 5.01 l/min with a standard deviation of 0.53 l/min, or 10.6%. After flow correction, this scatter decreased to 5.0% (P < 0.0001). With no bias, the corresponding limits of agreement decreased from +/- 1.06 to +/- 0.5 l/min after flow correction. In group B, the scatter decreased similarly and the limits of agreement also became +/- 0.5 l/min after flow correction. CONCLUSION: It was concluded that a single thermodilution cardiac output estimate using the flow-corrected equation is clinically feasible. This is obtained at the cost of a more complex computation and an extra pressure measurement, which often is already available. With this technique it is possible to reduce the fluid load to the patient considerably.