Ventricular Function
Left ventricular pressure-volume relations with transesophageal echocardiographic automated border detection: Comparison with conductance-catheter technique John Gorcsan III, MD, a Andre Denault, MD, b William A. Mandarino, MS, c and Michael R. Pinsky, MD b
Pittsburgh, Pa. Pressure-volume relations are important means used to assess left ventricular (LV) contractility; however, on-line volume acquisition has been limited to the invasive conductance catheter. The objective was to compare simultaneous measures of LV volume by transesophageal echocardiographic automated border detection (ABD) and conductance catheter and their respective pressure-volume relations during steady state and alterations in preload and contractility. Seven dogs had placement of high-fidelity pressure and conductance catheters, a vena caval balloon occluder, and a transesophageal probe. An automated Simpson's rule volume algorithm was used from the transverse four-chamber view. Inotropic modulation was induced with dobutamine in four dogs and propranolol in three. Relative changes in ABD volume were linearly related to conductance volume at steady state with group mean r = 0.93 ± 0.03, standard error of estimate (SEE)= 10 ± 2%. Changes in end-diastolic volume, end-systolic volume, and stroke work with caval occlusion were also significantly correlated: r = 0.93 ± 0.04, SEE = 3.6 ml; r = 0.89 ± 0.04, SEE = 3.8 ± 1.9 mi; and r = 0.86 ± 0.05, SEE = 40 ± 21 mJ, respectively. The overall bias was for absolute ABD volume to be less. Endsystolic and maximal elastance values by ABD were significantly higher than by the conductance method; baseline group average 4.97 ± 0.92 mm Hg/ml versus 2.70 ± 1.15 mm Hg/ml and 6.63 ± 1.66 mm Hg/ml versus 3.20 ± 1.37 mm Hg/ml (p < 0.05), respectively. However, the direction and relative magnitude of changes in elastance with inotropic modulation were similar. (AM HEARTJ 1996;131:544-52.)
Pressure-volume relations have been established as an important means of evaluating left ventricular (LV) performance. 1-3 Clinical applications, however, From the Divisions ofaCardiology, bAnesthesia/Critical Care Medicine, and CCardiothoracic Surgery, University of Pittsburgh. Received for publication July 5, 1995; accepted Aug. 23, 1995. Reprint requests: John Gorcsan III, MD, Division of Cardiology, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 152132582. Copyright © 1996 by Mosby-Year Book, Inc. 0002-8703/96/$5.00 + 0 4/1/69513
544
have been limited because on-line volume data acquisition has required surgical implantation of myocardial crystals or placement of an intraventricular multielectrode conductance catheter. 4-z° Recently we developed and validated a means to assess LV contractility with echocardiographic automated border detection (ABD) and pressure-area relations with area as a surrogate for volume. 1113 Although a pressure-sensing catheter is still required, this development has been of potential clinical importance because it obviates the need for a second intravascular intervention, and echocardiography may be noninvasive. More recently, an automated volume algorithm was developed. 14, 15 No previous study has investigated this volume algorithm in comparison with a simultaneous and continuous alternative measure of volume, such as the conductance catheter, nor its ability to be used for pressure-volume relations. Accordingly, the objectives were to evaluate this ABD volume system in comparison with the conductance catheter in steady state throughout the cardiac cycle, over a wide range of values induced by rapid changes in preload, and during alterations in inotropic state in a closed-chest canine model. METHODS Preparation. Seven dogs, weighing 20.6 ± 0.5 kg (18.2 to
24.6 kg), were studied. The protocol was approved by the Institutional Animal Care and Use Committee and conformed to the Position of the American Heart Association on Research Animal Use. All dogs were anesthetized with sodium pentobarbital (30 mg/kg induction, 1.0 mg/kg/hr maintenance with intermittent boluses if needed), endotracheally intubated, and mechanically ventilated. A 6Fr 11-pole multielectrode conductance catheter (Webster Laboratories, Irvine, Calif.) was inserted via the right internal carotid artery with its tip positioned in the LV apex by using fluoroscopic guidance. An LV micromanometer cathe-
Volume 131, Number 3
Gorcsan et al.
AmericanHeartJournal
545
Fig. 1. Transesophageal echocardiographic image of left ventricle (LV) with apex down from this canine model with automated border detection (ABD) calculation of volume. LA, Left atrium; CC, conductance catheter.
Electrocardiogram
200 LV Pressure (ram Hg)
0 70 Conductance Volume (ml) ,0
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20 15 seconds Fig. 2. Simultaneous physiologic waveform data during inferior vena caval occlusion and release maneuvers.
ter (MPC-500 Millar, Houston, Tex.) was also placed from the right common carotid artery. A 40 mm Fogarty balloon catheter was inserted via the right femoral vein to the inferior vena cava. This balloon was intermittently partially filled with saline to occlude caval flow and rapidly alter preload. A single-plane 5 MHz transesophageal transducer was inserted to the midesophageal level and positioned to obtain the four-chamber imaging plane with the maximal view of the LV apex. The probe handle was held stationary by a mechanical support apparatus. Echocardiography. Images were recorded using a prototype ABD echocardiographic system (77035A, HewlettPackard, And0ver, Mass.) previously described. 1~,17 Briefly, the ultrasound radiofrequency backscatter char-
acteristics are analyzed and compared with an internal threshold to differentiate blood from tissue. An estimate of the blood/tissue interface is displayed as a colored line superimposed on the two-dimensional image (Fig. 1). The threshold was manually adjusted by the transmit, timegain compensation, and lateral gain controls as a compromise between lateral dropout from insufficient gain and cavity clutter from excessive gain by using visual assessment.11-13, ls-2oA limiting region of interest was then manually drawn immediately beyond the endocardium and across the mitral annulus at end-diastole.TM15 Time-gain compensation was increased in the left atrium adjacent to the mitral valve plane to maximize automated tracking of LV blood. The maximum length from the apex to the cen-
March 1996 American Heart Journal
Gorcsan et al.
546
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Dog
r
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12 11 9 6 10 13 9 10-+2
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*N = 250 d a t a p a i r s p e r dog.
ter of the m i t r a l a n n u l u s was selected, a n d the a u t o m a t e d volume algorithm was activated. The algorithm was able to t r a c k changes in LV length along t h e assigned axis online a n d calculate volume using a modification of Simpson's rule w i t h 20 equally spaced circular discs. 14,15 Gain settings were r e a d j u s t e d if needed to exclude the right v e n t r i c u l a r cavity from e n t e r i n g the region of i n t e r e s t during t r i a l v e n a caval occlusions. Conductance volume. The c a t h e t e r uses a 20 kHz cons t a n t - a m p l i t u d e c u r r e n t of 0.03 m A RMS between the proximal a n d distal electrodes. Signals were collected w i t h a conductance d a t a processor as previously described 6-9 (Leycom Sigma 5DF, Leyden, Netherlands). A n electrical field is g e n e r a t e d in equipotential planes between each of the intervening electrodes at r i g h t angles to the long axis of the catheter. LV blood volume between a n y two sensing electrodes is considered to be a disk bounded by the endocardial surfaces to the electrodes. Changes in volume are sensed as a change in resistance in the cross-sectional a r e a of each disk, w i t h a correction factor for one t h i r d of t h e apical segment. The s u m of all segments reflects total volume. Time-varying LV volume (Vt) is r e l a t e d to the m e a s u r e d conductance (Gt) b y the equation: Vt = ( l / a ) L 2 p
(Gt - Gp), in which u is an empirical slope coefficient of 0.8 for the Vt/Gt correlation, L is the distance between electrodes, p is the resistivity of blood m e a s u r e d ex vivo, Gt is the s u m of conductances between electrode pairs, and Gp is a signal error caused by parallel conductance of the curr e n t t h r o u g h the LV wall a n d s u r r o u n d i n g tissues. The volume offset caused by parallel conductance (Vc) was calculated by the hypertonic saline m e t h o d as previously described, with the equation: Vc = (1/a)(L 2 p) Gp. P a r a l l e l conductance is t h e n s u b t r a c t e d from the total conductance to m e a s u r e LV volume. 69 C o m p u t e r workstation. The ABD system was configu r e d to allow direct recording of the analog volume signal t h r o u g h a customized h a r d w a r e and software interface previously described, n, 12 A1! physiologic signals were digitized a t 150 Hz for display a n d storage on a computer workstation (Apollo C o m p u t e r Inc. Model DN3550, Chelmsford, Mass.) with pressure-volume loops plotted in real time. F o r the ABD pressure-volume loops, the pressure signal was plotted with a variable delay, m e a n 13 _+ 19 msec (range 0 to 66 msec) to correct the 33 msec t e m p o r a l resolution of the ABD system. The a m o u n t of del a y was a d j u s t e d for each r u n by aligning the point immediately preceding isovolumic contraction on the pressure waveform with the first occurrence of m a x i m a l volume. No time a d j u s t m e n t was m a d e for the conductance pressurevolume loops. Protocol. To assess steady-state m e a s u r e s of LV volume t h r o u g h o u t the cardiac cycle, simultaneous conductance a n d ABD volume were acquired during a p n e a at end-expiration to minimize c a r d i o p u l m o n a r y interactions. 21 Acute alterations in preload were t h e n induced by inferior vena caval balloon occlusions (Fig. 2). To d e t e r m i n e the overall v a r i a b i l i t y of pressure-volume relations by the two techniques in the s a m e h e a r t u n d e r the same control conditions, a m i n i m u m of two successive apneic caval occlusions was performed, s e p a r a t e d by - 5 min. The effects of altering contractility by inotropic modulation on pressure-volume relations were t h e n investigated in a subset of these
Volume 131, Number 3 American Heart Journal
Gorcsan et al.
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T a b l e II. R e l a t i o n of a u t o m a t e d b o r d e r d e t e c t i o n v o l u m e to c o n d u c t a n c e c a t h e t e r v o l u m e d u r i n g a l t e r a t i o n s i n p r e l o a d End-diastolic volume Dog 1 2 3 4 5 6 7 Mean ± SD
Beats 29 72 59 59 41 53 59 53 ± 13
r 0.94 0.91 0.89 0.93 0.98 0.88 0.97 0.93 ± 0.04
SEE(ml) 2.7 3.1 6.6 6.1 3.4 2.0 1.1 3.6 ± 1.9
Slope 1.08 1.23 1.91 1.97 3.41 1.17 2.16 1.85 ± 0.75
Intercept -2 -3 13 -31 -80 17 -24 -16 ± 31
SEE(ml) 3.1 2.0 6.6 5.4 4.9 1.5 1.6 3.6 ± 1.9
Slope 1.15 1.10 1.83 1.87 3.40 1.17 2.48 1.86 ± 0.79
Intercept -6 3 13 -12 -72 11 -31 -13 ± 28
SEE(mJ) 37 32 29 71 74 19 19 40 ± 21
Slope 0.80 1.56 1.91 1.24 1.89 1.07 2.22 1.53 ± 0.48
Intercept 9 -103 28 52 65 66 55 25 ± 55
End-systolic volume Dog 1 2 3 4 5 6 7 Mean ± SD
Beats 29 72 59 . 59 41 53 59 53 ± 13
r 0.86 0.88 0.83 0.92 0.94 0.84 0.93 0.89 ± 0.04 Stroke work
Dog 1 2 3 4 5 6 7 Mean ± SD
Beats 29 72 59 59 41 53 59 53 ± 13
r 0.83 0.91 0.93 0.86 0.86 0.75 0.88 0.86 ± 0.05
dogs. F o u r dogs h a d d o b u t a m i n e i n f u s e d as a p o s i t i v e ino t r o p e a t 2-5 ~ g / k g / m i n . T h r e e dogs h a d a 3 m g b o l u s of propranolol infused as a negative inotrope. Once steadys t a t e c o n d i t i o n s w e r e a c h i e v e d , c a v a l occlusion m a n e u v e r s w e r e r e p e a t e d to c a l c u l a t e p r e s s u r e - v o l u m e r e l a t i o n s . Data a n a l y s i s . All p h y s i o l o g i c s i g n a l s w e r e t r a n s f e r r e d
into a customized program written in ASYST software ( A S Y S T S o f t w a r e T e c h n o l o g i e s , Inc., R o c h e s t e r , N.Y.). 11-13 S i m u l t a n e o u s s t e a d y - s t a t e m e a s u r e s of L V v o l u m e b y conductance catheter and transesophageal ABD were compared by plotting 250 consecutive digitized data pairs for e a c h dog (four to six b e a t s ) . S i m u l t a n e o u s p r e s s u r e -
March 1996 548
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pressure-volume indices of left ventricular contractility End-systolic elastance Ees (ram H g / m l )
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volume loops were plotted during inferior vena caval occlusions. Signals in the loop p r o g r a m were low-pass illt e r e d using the inverse F o u r i e r t r a n s f o r m of the B l a c k m a n window with a cut-off frequency set at 50 H z to eliminate high-frequency noise, as previously described. 1113 This filter h a s been shown not to a l t e r the physiologic signal s p e c t r u m while s u p p r e s s i n g electromagnetic interfer-
ence. 22 D a t a sets were divided into cardiac cycles from the R wave of the ECG, allowing the u s e r to eliminate ectopic beats. These p a r a m e t e r s were determined: end-diastolic volume, end-systolic volume, stroke work (f p r e s s u r e d volume), end-systolic elastance, and time-varying elastance, E(t), for m a x i m a l elastance. End-systolic elastance was the slope of the m a x i m u m pressure/volume points using an
131, Number 3 American Heart Journal Volume
automated iterative linear regression method.I, s E(t) was derived every- 7 msec from linear regression of the isochronous pressure-volume points of differently loaded beats beginning with end diastole and continuing past the end systole using the equation: E(t) = P(t)/[V(t) - Vo(t)], where E(t) = time-varying elastance, P = pressure, V = volume, t = time, Vo = volume axis intercept. The maximal value of E(t) was defined as maximal elastance) 4, ~-s Statistics. Steady-state conductance and ABD volume values were analyzed by the Bland-Altman method for assessing agreement between two methods of clinical measurement. 23 To determine the relation of relative changes in volume signals throughout the cardiac cycle, data were normalized to their respective minimum and maximum values and correlated using least squares linear regression analysis. Alterations in end-diastolic volume, end-systolic volume, and stroke work induced by caval occlusion were also assessed by least squares linear regression and Bland-Altman analysis. The respective variability of endsystolic elastance and maximal elastance calculations with ABD and conductance volume methods were reported as the difference/mean values for repeated measures. Endsystolic and maximal elastance values by the ABD method were compared with similar measures by the conductance method by using an unpaired t test. Changes in contractility induced by inotropic modulation were compared with an analysis of variance for repeat maneuvers. The degree of change in contractility by the respective methods was evaluated by linear regression of the percentage change in end-systolic elastance over baseline values. Data are presented as mean _+ standard deviation. Significance corresponds to p < 0.05.
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were less by the echocardiographic m e t h o d with overall bias o f - 1 0 ml, - 8 ml, and - 8 0 mJ, respectively (Fig. 5). Differences in respective volume values d u r i n g caval occlusion a p p e a r e d g r e a t e s t with l a r g e r v e n t r i c u l a r volumes. Calculations of contractility. Pressure-volume loops
RESULTS Steady-state volume. Results of baseline pooled L V
v o l u m e d a t a from seven dogs (3500 d a t a pairs with range: 15 to 65 ml), by B l a n d - A l t m a n analysis revealed a n overall bias o f - 1 5 ml for a u t o m a t e d echocardiographic m e a s u r e s c o m p a r e d with values obtained by the conductance c a t h e t e r , w i t h limits of a g r e e m e n t w i t h i n _+20 ml. The s t e a d y - s t a t e relation of relative changes in v o l u m e t h r o u g h o u t the cardiac cycle by echocardiographic a n d conductance methods were significantly l i n e a r (Fig. 3). T h e s e d a t a revealed a consistently close correlation of relative volu m e values with r = 0.93 _+ 0.03, S E E = 10 _+ 2% (Table I). Alterations in preload. The respective relations of end-diastolic volume, end-systolic volume, a n d stroke work from p r e s s u r e - v o l u m e loops b y the two m e t h ods with alterations in preload were also highly linear (Fig. 4 a n d Table II). Consistently close correlations of end-diastolic volume, end-systolic volume, and stroke work by ABD w i t h conductance values were observed: r-- 0.93 ± 0.04, 0.89 -+ 0.04, and 0.86 -+ 0.05, respectively. However, end-diastolic volume, end-systolic volume, a n d stroke w o r k values
with caval occlusion were available from all seven dogs u n d e r control conditions. One dog died of cardiogenic shock after propranolol bolus. Accordingly, d a t a sets were available from four dogs with d o b u t a m i n e and two dogs with propranolol infusions. No d a t a n e e d e d to be e l i m i n a t e d because of technically limited echocardiographic data. The variability of calculated m e a s u r e s of contractility from the identical r e p e a t e d inferior v e n a caval occlusions was similar for ABD and conductance methods, respectively: 2% _+ 18% versus 4% ± 15% for endsystolic elastance and 5% _+ 23% v e r s u s 5% _+ 24% for m a x i m a l elastance. The p e r c e n t a g e differences are shown with t h e i r r e t a i n e d sign to show bias a n d overall variability. This degree of variability was similar to previously r e p o r t e d values in animals with i n t a c t autonomic nervous systems, s, 11 End-systolic and m a x i m a l elastance relations were highly linear for e i t h e r volume m e t h o d (Fig. 6, Table III). As expected from these differences in absolute volume data, calculated elastance values were significantly g r e a t e r with the ABD volume t h a n the conductance volume. The ABD m e t h o d yielded elastance values t h a t were a p p r o x i m a t e l y twice those of the conduc-
March 1996
550
Gorcsan et al.
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tance method. Although absolute values differed, directional changes in contractility with inotropic modulation were predictably similar (Figs. 7, 8). Furthermore, the relative magnitude of change in contractility was similar with both methods with percentage change in end-systolic elastance values being significantly related with r = 0.73 (Fig. 9). DISCUSSION
This study demonstrates that relative steadystate changes in LV volume throughout the cardiac cycle and dynamic changes during caval occlusion or inotropic modulation are very similar by transesophageal ABD and conductance catheter in an intact canine model. The overall bias was for greater absolute volume values by the conductance method. Accord-
ingly, the variability, direction, a n d relative magnitude of change in pressure-volume relations were similar with either technique. Previous studies have shown close correlations of conductance volume with alternate measures such as electromagnetic flow in animals and contrast ventriculography in h u m a n beings.B, s, 9 ABD measures of ventricular cross-sectional area have also been closely correlated with changes in electromagnetic flow in animal and human experiments 11, 12, 18, 20 and with changes in true volume in an isolated canine preparation. 19 Differences in absolute volume values between conductance and ABD methods observed in this study may be accounted for by several possible mechanisms. First, the conductance catheter may overestimate LV volume by including the parallel conductance from the right ventricular cavity and the ventricular walls, although attempts were made to correct for this. 6-9 Second, ABD appears to have a tendency to underestimate LV volume. Marcus et al.24 reported an underestimation of end-diastolic cross-sectional area by ABD when compared with manually traced endocardial images by ultrafast computed tomography. They further suggested a cycle-specific pattern of underestimation from end diastole to end systole. This study, however, demonstrates a similar overall bias o f - 1 0 and -8 ml for end-diastolic and end-systolic volumes compared with simultaneous conductance values. A tendency to underestimate LV volume was also suggested by a comparison of ABD data with radionuclide data and also thermodilution stroke volume data in the same patients. 15,25 Morrisey et al. 14 reported LV volume underestimation of 11 _+ 15 ml by this ABD volume algorithm when compared with intraventricular balloon volume in an ejecting canine model. This underestimation may be related to reflected back-
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scatter within the LV cavity adjacent to the endocardial border, although a tendency to underestimate volume by conventional echocardiography has also been shown. 26 A third factor that m a y have contributed to echocardiographic volume underestimation in this study was the image artifact created by the multielectrode conductance catheter (Fig. 1). Finally, the use of the transesophageal transverse four-chamber view has been shown to underestimate LV volume in h u m a n beings because of incomplete imaging of the apex. 27, 28 Use of the longitudinal two-chamber view with a biplane or multiplane transesophageal probe may decrease the degree of volume underestimation.15 In spite of the differences in absolute values, on-line ABD measures of volume covary with conductance values in a consistent and reproducible pattern. As predicted by the lesser ABD volume values, eJ[astance values were consistently lower with the conductance method. Applegate et al. 1° also showed lower end-systolic elastance values from conductance volume when compared to LV volume measured by three pairs of ultrasonic endocardial crystals in a canine model. They concluded that the gain and offset of the conductance catheter are constant during steady state but vary with caval occlusion, reporting a greater progressive decrease in conductance volume. This m a y be related, in part, to changes in parallel conductance from decreases in right ventricular volume that are observed to precede decreases in LV volume with inferior vena caval occlusion. They also observed the direction and magnitude of change in contractility by inotropic modulation to be very similar, as we observed in this study. Limitations. A limitation of this study is that a third standard of reference for LV volume was not employed for comparison. This would not have been technically possible in our closed-chest animal preparation. Accordingly, the exact causes for the differences in volume data between the ABD and conductance catheter methods can only be inferred. However, these findings are consistent with a substantial body of data from previous separate studies that used ABD or conductance catheter methods.10, 14, 15, 24, 25 A potential limitation of the ABD system is the operator dependence of the gain settings. Although visual-image interpretation to adjust gain settings may be somewhat subjective, the reproducibility and reliability of ABD data have been documented to be satisfactory if a technically adequate echocardiographic image is possible. 16-18 Consistently high-technical-quality images could be obtained with transesophageal echocardiography in our study. These data further support the stability
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and reproducibility of predicting changes in LV volume on-line with ABD. Another potential limitation of this tomographic imaging method is in assessing left ventricles with regional wall-motion abnormalities. Because three-dimensional volume is calculated from two-dimensional data, caution should be e m ployed when assessing patients with significant segmental dysfunction. 29 Another limitation of this technique is that measurement error may be introduced if there is translational movement of the heart with respect to the stationary transducer. Translational movement from respirations in this study were minimized by recording all data during end-expiratory apnea. In conclusion, on-line measures of LV volume by transesophageal ABD are closely related to conductance catheter volume, and the direction and magnitude of change in end-systolic pressure-volume relations were predictably similar, although absolute values differed. Although a pressure-sensing catheter was still required, an advantage of the echocardiographic method is that a second intravascular intervention with its associated risks may be avoided. Furthermore, there is potential for this ABD technique to used noninvasively in human beings. 3° This echocardiographic method has promise to extend the application of pressure-volume analyses of LV performance to clinical settings not previously possible. REFERENCES
1. Suga H, Sagawa K, Shoukas AA. Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 1973;32:314-22. 2. Khalafbeigui F, Suga H, Sagawa IC Left ventricular systolic pressurevolume area correlates with oxygen consumption. Am J Physiol 1979; 237:H566-9. 3. Glower DD, Spratt, JA, Snow ND, Kabas JS, Davis JW, Olsen CO, Tyson GS, Sabiston DC, Rankin JS. Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work. Circulation 1985;5:994-1009. 4. Little WC, Freeman GL, O'Rourke RA. Simultaneous determination of left ventricular end-systolic pressure-volume and pressure-dimension relationships in closed-chest dogs. Circulation 1985;6:1301-8. 5. Slinker BK, Glantz SA. End-systolic and end-diastolic ventricular interaction. Am J Physiol 1986;H1062-75. 6. Baan J, Aouw Joug TT, Kerkhof PLM, Moene RJ, Van Dijk AD, Van Der Velt ET, Koops J. Continuous stroke volume and cardiac output from intra-ventricular dimensions obtained with impedence catheter. Cardiovasc Res 1981;15:328-34. 7. McKay RG, Aroesty JM, Heller GV, Royal HD, Warren SE, Grossmau W. Assessment of the end-systolic pressure-volume relationship in human beings with the use of a time-varying elastance model. Circulation 1986;74:97-104. 8. Kass DA, Yamazaki T, Burkhoff D, Maughan WL, Sagawa K. Determination of left ventrlcular end-systolic pressure-volume relationships by the conductance (volume) catheter technique. Circulation 1986; 3:586-95. 9. Baan J, Van Der Velde ET, DeBrmn HG, Smeenk GJ, Koops, Van Dijk AD, Temmerman D, Senden J, Bruis B. Continuous measurement of left ventricular volume in animals and humans by conductance catheter. Circulation 1984;5:812-23.
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