ORIGINAL ARTICLE
Simultaneous measurement of nght and left ventricular volume by the conductance
catheter technique in the newbon
lamb
RH. Lopes Cardozo, M. de Vroomen, F. van Bel, J. Baan, P. Steendijk
Background. Measurement of absolute ventricular volume with the conductance catheter thnique has been documented extensively for the left ventride (LV). More recently, the same technique has been applied in studies of right ventricular (RV) performance. In the present study we performed simultaneous measurements ofLV and RVvolumes. Conversion of measured conductances to absolute volumes requires the assessment of slope factor alpha (a) and parallel conductance correction volume (Vc) for both the RV and LV. We investigated the magnitude and variability of these calibration factors during a typical study period of four hours. Methods. In five anaesthetised, ventilated newborn lambs, conductance catheters were introduced into the LV and RV and a thermodilution catheter was positioned in the pulmonary artery. Alphas and Vc's were detennined by thermodilution and hypertonic saline dilution, respectively, at one hourly intervals. At the same time points, biventricular haemodynamic parameters were obtained. Results were analysed by multiple linear regression analysis. Results. During the course of the experiments all haemodynamic parameters were stable. There were no significant changes in Vc or a for either ventride. RV-Vc was systematically higher than LV-Vc: both as absolute values and as percentage of the uncalibrated conductance signal (79% for RV, and R.H. Lopes Cardozo. Department of Neonatology, Juliana Children's Hospital, P0 Box 60605, 2506 LP The Hague. M. de Vroomen. J. Baan. P. Steendljk. Department of Cardiology, Leiden University Medical Centre, P0 Box 9600, 2300 RC Leiden. F. van Bel. Department of Neonatology, University Medical Centre Utrecht, P0 Box 8500, 3508 GA Utrecht.
Address for correspondence: P. Steendijk. E-mail: [email protected]
Netherlands Heart Joumal, Volume 11, Number 5, May 2003
49% for LV, respectively). This probably reflects the geometrical differences of the two ventrides. Right ventricular ejection fraction (RV-EF) was higher than left ventricular ejection fraction (LV-EF), and neither changed significantly during four hours. Conclusion. These results show that calibration factors a and Vc for the RV, as well as EF, show values that are consistent with the observed haemodynamic stability and in line with the LV factors. These results indicate that the conductance catheter method can be used satisfactorily for biventricular function assessment (NechHeartJ2003;11:203-9.) Key words: pressure-volume loops, ventricular function, right ventricle
The conductance catheter provides a continuous measurement of ventricular volume by means of an intra-cavitary multi-electrode catheter. Combined with a solid state pressure sensor incorporated in the same catheter, this instrument is used to measure ventricular pressure-volume loops from which various parameters of global systolic and diastolic ventricular function may be derived. Furthermore, by acquiring pressure-volume loops during a loading intervention, systolic and diastolic pressure-volume relations may be obtained. Such relations have proven to be particularly useful because they provide indices of systolic and diastolic ventricular function which are relatively independent of loading conditions and as such mainly reflect intrinsic myocardial properties ('contractility').'3 Generally, in cardiac disease various factors that determine cardiac pump function (contractility, loading conditions, heart rate) are abnormal, either directly as a consequence of the pathology or indirectly as a compensation mechanism. Likewise, treatment either by drugs, surgery, or with devices such as pacemakers may have direct or indirect effects on all ofthese factors. Therefore, the ability to quantify these factors independently is highly valuable in the evaluation of cardiac function. Instantaneous and continuous left ventricular (LV) volume measurements with the conductance catheter 203
Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newbom lamb
have been validated and widely used in both human and animal subjects.4 While mainly used in the LV, the conductance catheter is currently being evaluated for right ventricular (RV) volume measurements with in vitro studies5 as well as in vivo in rabbits,6 swine,7,8 sheep9 and man.'0"' It is generally agreed that evaluation of RV performance is important in pulmonary and cardiac disease states.'2 Accurate volume measurements with routinely used techniques have proven to be difficult due to the complex geometry and extensive trabecularisation of the RV, especially in the smaller newborn heart. Magnetic resonance imaging has been shown to be the most accurate technique to assess RV function so far.'3 However, the conductance catheter technique potentially circumvents the problems encountered with other ways of assessing RV volume. This technique is based on the continuous measurement of electrical conductance of the blood in the ventricle. The conductance signal is converted to a volume signal on the basis of a stacked-cylinder model and by taking into account the specific conductivity ofthe blood and the catheter electrode spacing. However, electrical conductance oftissues and fluids surrounding the ventricular cavity, generally called parallel conductance (GP), introduces an offset signal which must be corrected for. G' can be determined by injecting a bolus of hypertonic saline into the blood stream that transiently increases conductivity of the blood while parallel conductance is practically unaffected. From the conductance signal, obtained during passage of the bolus through the ventricle, one can determine the contribution of parallel conductance to the total conductance signal.4 In addition, the conductance signal, after correcting for parallel conductance, generally underestimates true volume. To amend this, slope factor alpha (a) has been introduced, which is determined by comparing the uncalibrated conductance derived (stroke) volume with an independent measurement such as thermodilution. Thus, the equation to convert conductance to volume contains two calibration factors, GP and a. Although, at least for the LV, these factors are reasonably independent of haemodynamic conditions,'4-15 they appear to have a substantial interspecies and
intersubject variability. Studies in our group have found that determination of GP for the LV with an intravenous injection of hypertonic saline correlates excellently with the conventional pulmonary artery injection.'6 This makes it possible to determine parallel conductance for both RV and LV from a single intravenous saline injection. Especially in the small subject where multiple saline injections interfere with the normal physiological state, reduction in the number of these injections is important.
Recently, several studies have presented simultaneous measurement of LV and RV volumes and pressures, which also opens the possibility to study 204
biventricular performance and ventricular interaction in physiological states and in cardiac and pulmonary diseases.'7-'9 The behaviour and comparative measurements of a and C31P for both ventricles over time are not known. We investigated the magnitude and variability ofboth calibration factors for both ventricles during a typical study period of four hours in closed chest newborn lambs. Methods The conductance catheter method This method, developed in our laboratory in Leiden,4'20 enables a continuous, on-line measurement ofabsolute ventricular volume. Briefly, the conductance catheter method is based on measuring the electrical conductance ofthe blood in the ventride, which is proportional to ventricular volume. Figure 1 shows the conductance catheter positioned in the leftventricle. Two electrodes in the apex and two electrodes above the aortic valve are used to set up a dual-field intra-cavitary electric field using a 20 kHz, 30 piA electric current (I). The remaining interposed electrodes are used pairwise to pick up segmental voltage differences (fr). Segmental conductance (Gi) is calculated according to Ohm's law as G = I/+, (note that conductance equals 1/resistance). A signal conditioner-processor (Sigma-5 DF, see below) generates the excitation currents and continuously measures the conductance of all five segments. Based on simple physics, the electrical conductance of a 'slice' of blood, delineated by two electrodes, is proportional to the specific electrical conductivity of blood (OB), inversely proportional to
Figure 1. Combined pressure-conductance catheter positioned in the kft ventrick. A 20kHz ekctricfeld isgenerated via two apical and two basal eectrodes using dual-field excitation (totalcurren; I - I+I2 -30 pA). Voltage differences (4k) between remaining eketrodes are measured pairwise to determine the electrical conductance offive segments (G. - IA.). For clarity only segment 2 isshown here, but allfive segments are meaured continuously. Note the solid state pressure sensor in the third segment.
Netherlands Heart Journal, Volume
II, Number 5, May 2003
Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newbom lamb
the thickness ofthe slice (thus to the electrode spacing, L), and directly proportional to the cross-sectional area (A) of the slice, thus Gi = (GB/L)-A,. The electrode spacing and specific blood conductivity (which is measured from a 5-ml blood sample using a special cuvette) are constant, but if during ejection or filling the cross-sectional area changes, this will be directly reflected in the measured conductance. Vice versa, the cross-sectional area may be determined from measured conductance as A, = (L/GB) Gi . By multiplying the cross-sectional area by its thickness, segmental volume is obtained: V, = A; L = (L2/OB)*Gi. Finally, total LV volume is obtained after summation of the segmental conductances (GTOT = IGQ) as VLV = (L2/UB).GTOT. In practice, this equation needs to be corrected for two factors, which will be explained briefly. The first factor is parallel conductance GP, which stems from the fact that not only the blood in the ventricle is conductive, but also the surrounding structures such as the myocardial wall and the lungs. These conductive parallel structures introduce an offset ('background') in the measurements, thus to obtain absolute LV volume GP must be determined and subtracted from the measured conductance: VLV = (L2/CGB).(GTOT- G). After correction for Gr the calculated volume is directly proportional to true volume, but generally underestimates it by a fixed percentage. This underestimation is mainly due to two factors. First there is a mismatch between the actual LV long axis and the measured segments and, generally, in the apical and the basal region some volume will not be measured. Second, in
the conversion of conductance to volume it is assumed that the electrical field is homogeneous in each segment, i.e. the equipotential planes are flat and parallel. In reality this is not entirely the case which also leads to underestimation.21'22 To amend this, Baan et al.' introduced the slope factor a which may be obtained by comparing conductance-derived stroke volume with an independent reference method, such as thermodilution: a= SVCONDUCTANCE / SVTHERMODILunON. Thus calibrated absolute volume is obtained as VLV = (1/a).(L2/aB).(GTOT -(i). Animal preparation Five newborn lambs, aged 4 to 12 days, weighing 3.1 to 7.8 kg, were anesthetised using continuous infusion with ketamine hydrochloride (7-30 mg/kg/h) and xylazine (1 mg/kg intramuscularly) after induction with ketamine hydrochloride (3 mg/kg intravenously). The animals were intubated, ventilated with the pressure-controlled Babylog 8000 ventilator (Drager Werk AB, Lubeck, Germany) and paralysed with pancuronium (0.2 mg/kg intravenously). Ventilator settings and oxygen supply were adjusted to maintain arterial PaO2 and PaCO2 in the normal range. An intravenous infusion of 2.5% glucose in 0.45% NaCl solution was continued throughout the study (10 ml/kg/h). Sodium bicarbonate was supplemented if the arterial pH was lower than 7.30 and the base-deficit more than 5 mmol/l. Arterial blood gasses and pH were measured using a Corning 178 pH/blood gas analyser (Corning, Halstead, UK).
Figure 2. Scbematic drawing (right panel) and a radiographic image (kft panel) of the animal instrumentation. Combined pressureconductance cateteri are positioned in the kft and right ventrick. A thermodilution cateter is placed in the pulmonary artery and a balloon occlusion catheter is positioned in the vena cava infrrior.
Netherlands Heart Journal, Volume 11, Number 5, May 2003
205
Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newborn lamb
Instrumentation 5 Fr or 6 Fr self-sealing sheaths were placed in both the left and right femoral arteries and veins. All catheters were positioned under fluoroscopic guidance. A 5 Fr Berman angiographic catheter (American Edwards Laboratories, Irvine, CA) was advanced to the ascending aorta to measure aortic pressure (PAO). A balloon catheter was placed in the inferior vena cava via the left or right femoral vein to change preload conditions for the ventricles. Via incisions in the neck, 5 Fr or 6 Fr self-sealing sheaths were inserted into the left carotid artery and left jugular vein and right jugular vein. For measuring ventricular volumes simultaneously with pressures, 5 Fr pig-tailed combined micromanometerconductance catheters (Millar Instruments, Houston, Tx, USA) were introduced into the LV via the left femoral artery and into the RV ventride via the right jugular vein. The catheters were connected to two Sigma-5 signal-conditioner-processors (CD-Leycom, Zoetermeer, the Netherlands) for calculation of ventricular volumes. A 20 kHz field was used for one catheter while the other was operated with a lower excitation frequency (16 kHz) to avoid cross talk between the two systems. Cardiac output measurements were done with a 5 Fr thermodilution catheter positioned into the pulmonary artery via the left or right femoral vein. Figure 2 shows both a schematic drawing and the radiographic image of the catheters in situ.
Calibration factors The instantaneous conductance signals, G(t), are converted to calibrated volume signals V(t) according to the following equation:
V(t) = (1/a).(L2/YB).[G(t) - GP] Here, a is a dimensionless slope factor, L the distance between the sensing electrodes, aB the conductivity of the blood and GP the conductance ofthe surrounding tissue. Note that parallel conductance correction volume (Vc) is defined as Vc = (L2/GB) GP. To determine parallel conductance, a small bolus (0.6 ml) ofhypertonic saline (10%) was injected into the inferior vena cava.4"16 In short, by gradually and transiently changing blood conductivity with hypertonic saline, one can extrapolate the relation of measured total conductance (i.e. ventricular blood conductance plus parallel conductance) versus blood conductivity to the point where blood conductivity hypothetically would be zero and thus the remaining total conductance represents GP only. The parallel conductances were determined as the mean of at least two repeat injections. Note that since the output ofthe Sigma-5 is (L2/a4)-G(t) rather than G(t), the hypertonic saline method yields the parallel conductance correction volume: Vc = (L2/B) GP. Alphas were determined by measuring cardiac output (CO) with the thermodilution technique and 206
comparing these values with simultaneous conductance catheter derived CO: a
=
COCONDUCTANCE/COTHERMODILUTION
Haemodynamic measurements Aortic pressure (PAO) and pulmonary artery pressure (PA,) were monitored continuously using Statham P23Db strain gauge transducers, and a Beckman R 612 (Beckman Instruments, Palo Alto, CA) or a Gould 2800s (Gould, Cleveland, Ohio) polygraph. RV and LVvolume, stroke volume (SV), ejection fraction (EF) and CO were analysed from the calibrated conductance catheter signals in a beat-to-beat fashion, using dedicated software. Reported data represent averaged values over the first ten steady-state beats ofeach run.
Experimental protocol After instrumentation, animals were allowed one hour to reach haemodynamic steady state. Subsequently, a's and Vc's for both LV and RV were assessed at one hourly intervals. At the same time points, biventricular haemodynamic parameters were obtained. Statistical analysis The purpose of the study was to assess Vc and a at sequential time points during the experiment and to determine interanimal variability and variability during the course of the study of both factors. The following multiple linear regression implementation of a repeated measures analysis of variance was used: y=
ao + I a.A
+
lT.Ta,23,24
where y represents the dependent variable of interest (Vc or a) and ae yields the mean value ofthis dependent variable at baseline. The following coding was used: the n-I dummy variables A account for between-animal differences allowing the n animals to have a different mean value. The standard deviation of the group of animal coefficients, aiA, is a measure of interanimal variability of the dependent variable. For the time points, reference coding with respect to baseline, dummy variables for T, were used.23 Data are represented as mean ± SEM. Results During the course of the experiments all haemodynamic parameters were stable and did not change significantly. Figure 3 shows the passage of the small bolus of hypertonic saline through the RV and subsequently the LV as measured by the conductance catheters in the respective ventricles as gradual changes in conductance signals. Both catheters pick up the signal ofthe passage of the hypertonic saline bolus in the other ventricle although only to a small degree. Table 1 gives the mean data for V,, a and EF for both ventricles during the course of the experiments. There was a considerable interanimal variability in Netherlands Heart Journal, Volume 11, Number 5, May 2003
Simultaneous measurement of right and left ventrcular volume by the conductance catheter technique in the newbom lamb
-
9.0
Right Ventricle
E E
8.5
>
7.5,
r
Left Ventricle
100R'-O0.RI'0S84
25
y- 4.71M+ 6.879
E 20 E
i
".23
Y
75 ~~~~~~~~~50
*
10 7.0
e
11.0
10~~~~~~~~~
E i0.5,
0
5
E
0
10 _~~~~~Vlm
-J
M 10.0,
> 9.5,
._.__.m...L........_
10
5
..
Figure 4. Typical end-stolic pressure-volume relations (ESPVR) for both RVand LVduring one single transient inflow reduction intrention induced by balloon occlusion ofthe inferiorvena cava. Note the diJerences in scalingforRVand LVpressure.
9.0
25
20' a)
3 to1 U) = Q 5,
5
10
Time (s)
Figure 3. R Vand LVpressure and conductance tracings recorded after injection ofa 0.6 ml bolus of ypertonic (10%) saline into the vena cava inferior. The passage ofblood with increasd conductivity caussan increas in conductancesignals dunng subsequentpassage through the RV and LV. Note that the conductance signals are uncalibrated (i.e. a=l and GP-O).
RV-Vc (15.7 ml), LV-Vc (6.1 mL), RV-a (0.39), and LV-a (0.76) in these experiments. This dearly warrants the assessment of the calibration factors in each individual animal. The statistical analysis did not reveal significant changes during the course of the experiments in Vc or a for either ventricle when corrected for the interanimal variability. RV-Vc was
systematically and significantly higher than LV-V, (p
Simultaneous measurement of nght and left ventricular volume by the conductance
catheter technique in the newbon
lamb
RH. Lopes Cardozo, M. de Vroomen, F. van Bel, J. Baan, P. Steendijk
Background. Measurement of absolute ventricular volume with the conductance catheter thnique has been documented extensively for the left ventride (LV). More recently, the same technique has been applied in studies of right ventricular (RV) performance. In the present study we performed simultaneous measurements ofLV and RVvolumes. Conversion of measured conductances to absolute volumes requires the assessment of slope factor alpha (a) and parallel conductance correction volume (Vc) for both the RV and LV. We investigated the magnitude and variability of these calibration factors during a typical study period of four hours. Methods. In five anaesthetised, ventilated newborn lambs, conductance catheters were introduced into the LV and RV and a thermodilution catheter was positioned in the pulmonary artery. Alphas and Vc's were detennined by thermodilution and hypertonic saline dilution, respectively, at one hourly intervals. At the same time points, biventricular haemodynamic parameters were obtained. Results were analysed by multiple linear regression analysis. Results. During the course of the experiments all haemodynamic parameters were stable. There were no significant changes in Vc or a for either ventride. RV-Vc was systematically higher than LV-Vc: both as absolute values and as percentage of the uncalibrated conductance signal (79% for RV, and R.H. Lopes Cardozo. Department of Neonatology, Juliana Children's Hospital, P0 Box 60605, 2506 LP The Hague. M. de Vroomen. J. Baan. P. Steendljk. Department of Cardiology, Leiden University Medical Centre, P0 Box 9600, 2300 RC Leiden. F. van Bel. Department of Neonatology, University Medical Centre Utrecht, P0 Box 8500, 3508 GA Utrecht.
Address for correspondence: P. Steendijk. E-mail: [email protected]
Netherlands Heart Joumal, Volume 11, Number 5, May 2003
49% for LV, respectively). This probably reflects the geometrical differences of the two ventrides. Right ventricular ejection fraction (RV-EF) was higher than left ventricular ejection fraction (LV-EF), and neither changed significantly during four hours. Conclusion. These results show that calibration factors a and Vc for the RV, as well as EF, show values that are consistent with the observed haemodynamic stability and in line with the LV factors. These results indicate that the conductance catheter method can be used satisfactorily for biventricular function assessment (NechHeartJ2003;11:203-9.) Key words: pressure-volume loops, ventricular function, right ventricle
The conductance catheter provides a continuous measurement of ventricular volume by means of an intra-cavitary multi-electrode catheter. Combined with a solid state pressure sensor incorporated in the same catheter, this instrument is used to measure ventricular pressure-volume loops from which various parameters of global systolic and diastolic ventricular function may be derived. Furthermore, by acquiring pressure-volume loops during a loading intervention, systolic and diastolic pressure-volume relations may be obtained. Such relations have proven to be particularly useful because they provide indices of systolic and diastolic ventricular function which are relatively independent of loading conditions and as such mainly reflect intrinsic myocardial properties ('contractility').'3 Generally, in cardiac disease various factors that determine cardiac pump function (contractility, loading conditions, heart rate) are abnormal, either directly as a consequence of the pathology or indirectly as a compensation mechanism. Likewise, treatment either by drugs, surgery, or with devices such as pacemakers may have direct or indirect effects on all ofthese factors. Therefore, the ability to quantify these factors independently is highly valuable in the evaluation of cardiac function. Instantaneous and continuous left ventricular (LV) volume measurements with the conductance catheter 203
Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newbom lamb
have been validated and widely used in both human and animal subjects.4 While mainly used in the LV, the conductance catheter is currently being evaluated for right ventricular (RV) volume measurements with in vitro studies5 as well as in vivo in rabbits,6 swine,7,8 sheep9 and man.'0"' It is generally agreed that evaluation of RV performance is important in pulmonary and cardiac disease states.'2 Accurate volume measurements with routinely used techniques have proven to be difficult due to the complex geometry and extensive trabecularisation of the RV, especially in the smaller newborn heart. Magnetic resonance imaging has been shown to be the most accurate technique to assess RV function so far.'3 However, the conductance catheter technique potentially circumvents the problems encountered with other ways of assessing RV volume. This technique is based on the continuous measurement of electrical conductance of the blood in the ventricle. The conductance signal is converted to a volume signal on the basis of a stacked-cylinder model and by taking into account the specific conductivity ofthe blood and the catheter electrode spacing. However, electrical conductance oftissues and fluids surrounding the ventricular cavity, generally called parallel conductance (GP), introduces an offset signal which must be corrected for. G' can be determined by injecting a bolus of hypertonic saline into the blood stream that transiently increases conductivity of the blood while parallel conductance is practically unaffected. From the conductance signal, obtained during passage of the bolus through the ventricle, one can determine the contribution of parallel conductance to the total conductance signal.4 In addition, the conductance signal, after correcting for parallel conductance, generally underestimates true volume. To amend this, slope factor alpha (a) has been introduced, which is determined by comparing the uncalibrated conductance derived (stroke) volume with an independent measurement such as thermodilution. Thus, the equation to convert conductance to volume contains two calibration factors, GP and a. Although, at least for the LV, these factors are reasonably independent of haemodynamic conditions,'4-15 they appear to have a substantial interspecies and
intersubject variability. Studies in our group have found that determination of GP for the LV with an intravenous injection of hypertonic saline correlates excellently with the conventional pulmonary artery injection.'6 This makes it possible to determine parallel conductance for both RV and LV from a single intravenous saline injection. Especially in the small subject where multiple saline injections interfere with the normal physiological state, reduction in the number of these injections is important.
Recently, several studies have presented simultaneous measurement of LV and RV volumes and pressures, which also opens the possibility to study 204
biventricular performance and ventricular interaction in physiological states and in cardiac and pulmonary diseases.'7-'9 The behaviour and comparative measurements of a and C31P for both ventricles over time are not known. We investigated the magnitude and variability ofboth calibration factors for both ventricles during a typical study period of four hours in closed chest newborn lambs. Methods The conductance catheter method This method, developed in our laboratory in Leiden,4'20 enables a continuous, on-line measurement ofabsolute ventricular volume. Briefly, the conductance catheter method is based on measuring the electrical conductance ofthe blood in the ventride, which is proportional to ventricular volume. Figure 1 shows the conductance catheter positioned in the leftventricle. Two electrodes in the apex and two electrodes above the aortic valve are used to set up a dual-field intra-cavitary electric field using a 20 kHz, 30 piA electric current (I). The remaining interposed electrodes are used pairwise to pick up segmental voltage differences (fr). Segmental conductance (Gi) is calculated according to Ohm's law as G = I/+, (note that conductance equals 1/resistance). A signal conditioner-processor (Sigma-5 DF, see below) generates the excitation currents and continuously measures the conductance of all five segments. Based on simple physics, the electrical conductance of a 'slice' of blood, delineated by two electrodes, is proportional to the specific electrical conductivity of blood (OB), inversely proportional to
Figure 1. Combined pressure-conductance catheter positioned in the kft ventrick. A 20kHz ekctricfeld isgenerated via two apical and two basal eectrodes using dual-field excitation (totalcurren; I - I+I2 -30 pA). Voltage differences (4k) between remaining eketrodes are measured pairwise to determine the electrical conductance offive segments (G. - IA.). For clarity only segment 2 isshown here, but allfive segments are meaured continuously. Note the solid state pressure sensor in the third segment.
Netherlands Heart Journal, Volume
II, Number 5, May 2003
Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newbom lamb
the thickness ofthe slice (thus to the electrode spacing, L), and directly proportional to the cross-sectional area (A) of the slice, thus Gi = (GB/L)-A,. The electrode spacing and specific blood conductivity (which is measured from a 5-ml blood sample using a special cuvette) are constant, but if during ejection or filling the cross-sectional area changes, this will be directly reflected in the measured conductance. Vice versa, the cross-sectional area may be determined from measured conductance as A, = (L/GB) Gi . By multiplying the cross-sectional area by its thickness, segmental volume is obtained: V, = A; L = (L2/OB)*Gi. Finally, total LV volume is obtained after summation of the segmental conductances (GTOT = IGQ) as VLV = (L2/UB).GTOT. In practice, this equation needs to be corrected for two factors, which will be explained briefly. The first factor is parallel conductance GP, which stems from the fact that not only the blood in the ventricle is conductive, but also the surrounding structures such as the myocardial wall and the lungs. These conductive parallel structures introduce an offset ('background') in the measurements, thus to obtain absolute LV volume GP must be determined and subtracted from the measured conductance: VLV = (L2/CGB).(GTOT- G). After correction for Gr the calculated volume is directly proportional to true volume, but generally underestimates it by a fixed percentage. This underestimation is mainly due to two factors. First there is a mismatch between the actual LV long axis and the measured segments and, generally, in the apical and the basal region some volume will not be measured. Second, in
the conversion of conductance to volume it is assumed that the electrical field is homogeneous in each segment, i.e. the equipotential planes are flat and parallel. In reality this is not entirely the case which also leads to underestimation.21'22 To amend this, Baan et al.' introduced the slope factor a which may be obtained by comparing conductance-derived stroke volume with an independent reference method, such as thermodilution: a= SVCONDUCTANCE / SVTHERMODILunON. Thus calibrated absolute volume is obtained as VLV = (1/a).(L2/aB).(GTOT -(i). Animal preparation Five newborn lambs, aged 4 to 12 days, weighing 3.1 to 7.8 kg, were anesthetised using continuous infusion with ketamine hydrochloride (7-30 mg/kg/h) and xylazine (1 mg/kg intramuscularly) after induction with ketamine hydrochloride (3 mg/kg intravenously). The animals were intubated, ventilated with the pressure-controlled Babylog 8000 ventilator (Drager Werk AB, Lubeck, Germany) and paralysed with pancuronium (0.2 mg/kg intravenously). Ventilator settings and oxygen supply were adjusted to maintain arterial PaO2 and PaCO2 in the normal range. An intravenous infusion of 2.5% glucose in 0.45% NaCl solution was continued throughout the study (10 ml/kg/h). Sodium bicarbonate was supplemented if the arterial pH was lower than 7.30 and the base-deficit more than 5 mmol/l. Arterial blood gasses and pH were measured using a Corning 178 pH/blood gas analyser (Corning, Halstead, UK).
Figure 2. Scbematic drawing (right panel) and a radiographic image (kft panel) of the animal instrumentation. Combined pressureconductance cateteri are positioned in the kft and right ventrick. A thermodilution cateter is placed in the pulmonary artery and a balloon occlusion catheter is positioned in the vena cava infrrior.
Netherlands Heart Journal, Volume 11, Number 5, May 2003
205
Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newborn lamb
Instrumentation 5 Fr or 6 Fr self-sealing sheaths were placed in both the left and right femoral arteries and veins. All catheters were positioned under fluoroscopic guidance. A 5 Fr Berman angiographic catheter (American Edwards Laboratories, Irvine, CA) was advanced to the ascending aorta to measure aortic pressure (PAO). A balloon catheter was placed in the inferior vena cava via the left or right femoral vein to change preload conditions for the ventricles. Via incisions in the neck, 5 Fr or 6 Fr self-sealing sheaths were inserted into the left carotid artery and left jugular vein and right jugular vein. For measuring ventricular volumes simultaneously with pressures, 5 Fr pig-tailed combined micromanometerconductance catheters (Millar Instruments, Houston, Tx, USA) were introduced into the LV via the left femoral artery and into the RV ventride via the right jugular vein. The catheters were connected to two Sigma-5 signal-conditioner-processors (CD-Leycom, Zoetermeer, the Netherlands) for calculation of ventricular volumes. A 20 kHz field was used for one catheter while the other was operated with a lower excitation frequency (16 kHz) to avoid cross talk between the two systems. Cardiac output measurements were done with a 5 Fr thermodilution catheter positioned into the pulmonary artery via the left or right femoral vein. Figure 2 shows both a schematic drawing and the radiographic image of the catheters in situ.
Calibration factors The instantaneous conductance signals, G(t), are converted to calibrated volume signals V(t) according to the following equation:
V(t) = (1/a).(L2/YB).[G(t) - GP] Here, a is a dimensionless slope factor, L the distance between the sensing electrodes, aB the conductivity of the blood and GP the conductance ofthe surrounding tissue. Note that parallel conductance correction volume (Vc) is defined as Vc = (L2/GB) GP. To determine parallel conductance, a small bolus (0.6 ml) ofhypertonic saline (10%) was injected into the inferior vena cava.4"16 In short, by gradually and transiently changing blood conductivity with hypertonic saline, one can extrapolate the relation of measured total conductance (i.e. ventricular blood conductance plus parallel conductance) versus blood conductivity to the point where blood conductivity hypothetically would be zero and thus the remaining total conductance represents GP only. The parallel conductances were determined as the mean of at least two repeat injections. Note that since the output ofthe Sigma-5 is (L2/a4)-G(t) rather than G(t), the hypertonic saline method yields the parallel conductance correction volume: Vc = (L2/B) GP. Alphas were determined by measuring cardiac output (CO) with the thermodilution technique and 206
comparing these values with simultaneous conductance catheter derived CO: a
=
COCONDUCTANCE/COTHERMODILUTION
Haemodynamic measurements Aortic pressure (PAO) and pulmonary artery pressure (PA,) were monitored continuously using Statham P23Db strain gauge transducers, and a Beckman R 612 (Beckman Instruments, Palo Alto, CA) or a Gould 2800s (Gould, Cleveland, Ohio) polygraph. RV and LVvolume, stroke volume (SV), ejection fraction (EF) and CO were analysed from the calibrated conductance catheter signals in a beat-to-beat fashion, using dedicated software. Reported data represent averaged values over the first ten steady-state beats ofeach run.
Experimental protocol After instrumentation, animals were allowed one hour to reach haemodynamic steady state. Subsequently, a's and Vc's for both LV and RV were assessed at one hourly intervals. At the same time points, biventricular haemodynamic parameters were obtained. Statistical analysis The purpose of the study was to assess Vc and a at sequential time points during the experiment and to determine interanimal variability and variability during the course of the study of both factors. The following multiple linear regression implementation of a repeated measures analysis of variance was used: y=
ao + I a.A
+
lT.Ta,23,24
where y represents the dependent variable of interest (Vc or a) and ae yields the mean value ofthis dependent variable at baseline. The following coding was used: the n-I dummy variables A account for between-animal differences allowing the n animals to have a different mean value. The standard deviation of the group of animal coefficients, aiA, is a measure of interanimal variability of the dependent variable. For the time points, reference coding with respect to baseline, dummy variables for T, were used.23 Data are represented as mean ± SEM. Results During the course of the experiments all haemodynamic parameters were stable and did not change significantly. Figure 3 shows the passage of the small bolus of hypertonic saline through the RV and subsequently the LV as measured by the conductance catheters in the respective ventricles as gradual changes in conductance signals. Both catheters pick up the signal ofthe passage of the hypertonic saline bolus in the other ventricle although only to a small degree. Table 1 gives the mean data for V,, a and EF for both ventricles during the course of the experiments. There was a considerable interanimal variability in Netherlands Heart Journal, Volume 11, Number 5, May 2003
Simultaneous measurement of right and left ventrcular volume by the conductance catheter technique in the newbom lamb
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Figure 4. Typical end-stolic pressure-volume relations (ESPVR) for both RVand LVduring one single transient inflow reduction intrention induced by balloon occlusion ofthe inferiorvena cava. Note the diJerences in scalingforRVand LVpressure.
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Figure 3. R Vand LVpressure and conductance tracings recorded after injection ofa 0.6 ml bolus of ypertonic (10%) saline into the vena cava inferior. The passage ofblood with increasd conductivity caussan increas in conductancesignals dunng subsequentpassage through the RV and LV. Note that the conductance signals are uncalibrated (i.e. a=l and GP-O).
RV-Vc (15.7 ml), LV-Vc (6.1 mL), RV-a (0.39), and LV-a (0.76) in these experiments. This dearly warrants the assessment of the calibration factors in each individual animal. The statistical analysis did not reveal significant changes during the course of the experiments in Vc or a for either ventricle when corrected for the interanimal variability. RV-Vc was
systematically and significantly higher than LV-V, (p
