An intra-arterial catheter (Seldi Cath 3F; Plastimed, St. Leu Lafôret, France) carrying a pressure head (Grass-Telefactor; Astro-Med, West Warwick, RI, U.S.A.) for continuous intra-arterial pressure recording was inserted into the left radial artery. The photoplethysmographic cuffs of a finger pressure device (Portapres®; TNO TPD Biomedical Instrumentation, Amsterdam, The Netherlands) were placed on the third and fourth fingers of the contralateral hand. The subject’s arms were sustained by a scarf fixed around the neck, in order to avoid compression due to handlebar grasping. The gain of the intra-arterial pressure head was 100 mmHg/V, with a 0 mmHg signal set at 0 V (ambient air). The Portapres®signal was calibrated following the procedure indicated by the manufacturer. The height adjustment sensor and the reference were positioned according to the manufacturer’s instructions. Pulse pressure signals from both devices and the ECG were digitized by means of a 16-bit A/D converter (MP100, Biopac Systems, Santa Barbara, CA, U.S.A.) operated by commercial software (ACK100W;
Biopac Systems) running on a PC. Acquisition rate was set at 100 Hz. Exercise was performed on an electromagnetically braked cycle ergometer (Ergomed 840L; Siemens, Erlangen, Germany).
The pressure profiles were fed to a computer running the Beatscope® software program (version 1.0; TNO-TPD Biomedical Instrumentation), implementing the Modelflow®model [Wesseling et al., 1993]. The pulse pressure profiles were analysed off-line to determine beat-by-beat systolic (Ps), diastolic (Pd) and mean (Pm) blood pressures. Beat-by-beat HR and SV were then calculated by using the procedure incorporated in the Beatscope®software. Beat-by-beat .
Q was then calculated as the product of SV times the corresponding HR.
2 P
ROTOCOLAfter insertion of the arterial catheter, the subject sat on the ergometer and the Portapres®cuff was positioned. After 5 min of recording at rest, exercise at 50 W was started for 10 min.
After a 10 min recovery, the 100 W exercise started, again for a 10 min duration, followed by a 10 min recovery. The pulse pressure profiles from both the intraarterial catheter and the Portapres®device were recorded continuously during the entire protocol.
3 S
TATISTICAL ANALYSISData are presented as means ± S.D. Each mean value is the mean of all the beats at rest and at the steadystate exercise levels (from fourth min of exercise onwards) recorded on all subjects, n was 10048 for each parameter. The effects of the measurement site (radial artery compared with the fingertip) were evaluated by Student’s t test for paired observations. Linear regression was calculated by the least-squares method using the procedure of Brace [Brace, 1977]. Agreement between the two methods of measurements was assessed by means of Bland–Altman analysis [Bland et al., 1986]. Significance level was set at p<0.05.
4 R
ESULTSAn example of pulse pressure tracings recorded simultaneously at rest from the radial artery and from the finger is shown in Figure 9. Absolute pressure values are systematically higher in the radial artery than the finger. Moreover, the shape of the pressure profiles differed between the two recordings: the tracings from the fingertip showed a larger dicrotic incision and a more rapid pressure decrease during diastole.
Figure 10. Example of intra-arterial (upper) and finger (lower) pulse pressure profiles recorded at rest
First study
The mean values of Ps, Pd and Pm at rest and at the steady state of the two investigated workloads from both the intra-arterial pressure head and the Portapres®finger cuff are shown in Table 1. The values from the finger were significantly and systematically lower than those from the radial artery. In addition, the S.D. of Ps, Pdand Pmobtained from the Portapres®finger cuff, with the exception of resting Ps, were significantly (p<0.05) greater than those from the radial artery.
Table 1: Means Ps, Pd, Pm and .
Q at rest and exercise steady state (50 and 100 W) measured from the intra-arterial pressure head and the finger device (Portapres®). Values are
± SD. Each mean value is the result of 10’048 measurements.
Intra arterial The corresponding mean values (n=10’048) of the values .
Qpia and .
Qporta are also shown in
Table 1. The mean steady-state .
Qporta values were significantly (p<0.05) and systematically
higher than those for .
Qpia. In addition, as for Ps, Pd and Pm, the S.D. of .
Qporta were systematically larger than those of .
Qpia. Figure 10 shown the .
Qporta from all heart beats in all
subjects as a function of the corresponding .
Qpia. The corresponding linear relationship is described by the following regression equation: y=1.55x-3.02, R2 =0.640.
Figure 11. .
Qporta as a function of .
Qpia.
All individual beats at rest and exercise are reported (n=10’048). The continuous line is the regression line, the broken line is the equality line.
Figure 12. Bland–Altman analysis of the differences between .
Qporta and .
Qpia as a function of the average value of the two values for each beat.
The line relating these parameters has a significant positive slope ( y=0.48 x −2.77 l.min-1, [x]=1 l.min-1, r=0.603).
The results of the Bland–Altman analysis are shown in Figure 11. The bias (mean of the difference .
Qporta - .
Qpia) was 1.44 litre min-1, with S.D. (precision) of 2.84 litre · min-1 ; the 95%
confidence interval ranged from -4.12 to +7.01 litre · min-1. The line regression shown in Figure 11 has a significant positive slope (y= 0.48x-2.77, r=0.603). This indicates that the
First study slope of the regression line between the individual .
Qporta and .
Qpia is significantly greater than 1. Thus, .
Qporta carries along a systematic error with respect to the reference value, .
Qpia, for .
Q
> 5 l.min-1.
5 D
ISCUSSIONEquivalent pulse pressure tracings from the finger and main arteries should provide equivalent Q. values. If this were the case, the relationship between beat-by-beat .
Q values determined from pulse pressure profiles recorded from the finger and the corresponding beat-by-beat .
Q values from the same pulse pressure profiles recorded simultaneously from a more proximal artery (in the present case the radial artery) would be described the line of equality (the line on which both sets of data would lie if they were identical). However, the main finding of the present study is that the slope of the line relating beat-by-beat .
Qportato beat-by-beat .
Qpiais significantly higher than that of the equality line, as demonstrated by the Bland–Altman analysis (Figure 11). This indicates that the pulse pressure profiles recorded from the finger yield an overestimate of beat-by-beat .
Q with respect to the corresponding values obtained from the radial artery. From the slope of the regression line reported in Figure 10, this overestimate appears to be 55%.
That fingertip pressure profiles provide unreliable .
Q values has been shown in a previous study [Houtman et al., 1999] in which a comparison of .
Qportawith .
Q determined by CO2 rebreathing at rest and at the steady state of submaximal workloads was carried out. In that study the average difference (bias) between the two methods amounted to 2.27 ± 3.90 litre min-1. In the present study, the comparison between .
Qpia and .
Qporta suggested that the
inaccuracy reported by Houtman [Houtman et al., 1999] could be due, at least partly, to an error persisting by the peripheral site of pulse pressure recording and not to the pressure pulse principe. Since we were not authorized to place a catheter in the aorta for the purposes of this study, the radial artery was retained as the site for invasive pulse pressure profile recordings, despite the fact that the Modelflow®makes use of constants determined on the post mortem
typical structure of an elastic artery [Laurent et al., 1994], and the error introduced with respect to the aorta is expected to be negligible in the present context.
In addition, Wesseling [Wesseling et al., 1993], measured .
Q by Modelflow®from the radial artery, and concluded that the .
Q values obtained from this site were sufficiently accurate with respect to computations from the aorta, despite the changes in flow characteristics while moving from the latter to the former site. On these bases, the use of radial artery pressure profiles as a reference site in the present study seemed to be justified.
Non-invasive photoplethysmographic recordings of pulse pressure, are made on peripheral small arteries of the finger, and possess lower absolute pressure values [Idema et al., 1989;
Gizdulich et al., 1997] as shown in Table 1, and a different pulse form [Remington &
Wood, 1956] as indicated in Figure 9. The lower blood pressure values observed in the finger arteries may be explained (if real) either by the significant hydraulic resistance to flow with respect to more proximal arteries, or by the vascular tone prevailing at the finger level. If the former explanation is correct, different relationships between pulse pressure and flow may be expected when compared to the radial artery, and this may explain most of the significant differences between .
Qportaand .
Qpiaobserved in the present study.
If alternatively, the second explanation is correct, the answer would only be obtained after performing a similar experiment following administration of a blood pressure enhancer, such as phenylephrine.
The computation algorithm implemented in the Beatscope® software includes a waveform filtering procedure aimed at reconstructing the brachial artery pressure pulse from the finger arterial pressure, and a correction for pressure level is also introduced [Bos et al., 1996;
Gizdulich et al., 1997]. This correction procedure improves the accuracy of the method by reducing the pressure level differences between the two sites. Nevertheless, the data in the present study show that these corrections are insufficient to provide equivalent values of
Q. portaand .
Qpia, especially during exercise.
The so-called characteristic impedance (cZ) method is another earlier means of calculating .
Q from pulse pressure analysis [Warner et al., 1953; Kouchoukos et al., 1970; Alderman et al., 1972]. Also this method was modified in order to take into account the effect of changes in blood pressure, vascular tone, HR and vascular resistance that occur during exercise,
First study hypervolaemia and application of lower body negative pressure contour [Stok et al., 1993;
Antonutto et al., 1994; Antonutto et al., 1995]. However, the corrections incorporated in the cZ method are based on empirical coefficients, whereas Modelflow®, although relying on the post mortem elastic characteristics of the major aortic vessels, exploits a theoretical model of the vascular system. Finally, the variations of resting .
Q with the cZ method turned out to be larger than with Modelflow®[Stok et al., 1993].
When only changes in .
Q with respect to baseline values are to be investigated, Modelflow® applied to non-invasive continuous recordings of pulse pressure profiles from the finger could be a reliable method for .
Q measurements. Because the error shown for .
Qporta is systematic, the relative .
Q changes obtained with Modelflow are probably sufficiently accurate, even though they are less reliable than those obtained from other established steady-state methods [Stok et al., 1993; Wesseling et al., 1993; Houtman et al., 1999; Remmen et al., 2002].
Absolute .
Q values computed from non-invasive pulse pressure profiles from the finger were found, however, to be significantly different from those obtained from the radial artery.
Therefore, if radial artery pressure profiles provide accurate .
Q values [Wesseling et al., 1993], absolute non-invasive .
Q values with Modelflow® should not be used without correcting them with a calibration factor obtained previously by means of an independent established method. This conclusion is similar to that attained by others for the cZ method [Stok et al., 1993; Antonutto et al., 1994; Antonutto et al., 1995]. In the accompanying paper (second study), the accuracy of Modelflow®applied to non-invasive pulse pressure profiles is analysed and a correction procedure proposed.
S ECOND S TUDY
1 M
ETHODS1.1 SUBJECTS
Experiments were carried out on nine male healthy subjects (age, 24.6 ± 2.96 years; body mass, 74.6 ± 6.90 kg; and height, 180.4 ± 4.03 cm). All subjects were informed about the procedures and the potential risks of the experiments and they all signed an informed consent form. The study was approved by the Ethics Committee of the School of Medicine of Udine and complied with the Declaration of Helsinki .
1.2 METHODS Reference .
Q ( .
QC2H2 ) was measured by means of an open-circuit acetylene technique [Barker et al., 1999]. At rest and steady state exercise, the subject inhaled a gas mixture containing 21% O2, 6% helium and 1.5% acetylene balanced with nitrogen for a total of 20-25 breaths.
Gas concentrations during breathing of the mixture were monitored continuously on a mass spectrometer (Airspec 2200, Gillingham, Kent, U.K.). Inspired and expired gas volumes were determined by an ultrasonic flowmeter (Tuba; GHG, Zurich, Switzerland). Gas fractions and flow signals were calibrated before each experiment by means of gas mixtures of known composition and by means of predefined inspiratory and expiratory volumes obtained by using a calibrated 3 litres syringe (Hans Rudolph, Kansas City, MO, U.S.A.). At each .
QC2H2 measurement, a pneumatic piston operated a shuttle valve (Hans Rudolph) placed between the ultrasonicflowmeter and a two-way non-rebreathing valve. The pneumatic servomechanism (Burosoft, Udine, Italy) deviated the inflow from ambient air to the acetylene-containing gas mixture administered from a high-pressure gas cylinder via a Douglas bag. .
QModelflow®was determined continuously at rest and during exercise from arterial pulse pressure profiles recorded non-invasively by using a Portapres® system (TNO-TPD Biomedical Instrumentation, Amsterdam, The Netherlands). The photoplethysmographic cuffs of Portapres® was positioned on the index and middle fingers. The Portapres® signal was calibrated following the procedure indicated by the manufacturer. The height adjustment sensor and the reference were positioned according to the manufacturer’s instructions.
Second study Pulse pressure, gas fractions and respiratory flow signals were digitized by means of a 16-bit A/D converter (MP100; Biopac Systems, Santa Barbara, CA, U.S.A.) operated by commercial software (ACK100W; Biopac Systems) running on a PC. Acquisition rate was set at 100 Hz.
Exercise was performed on an electromagnetically braked cycle ergometer (Ergomed 840L;
Siemens, Erlangen, Germany).
The pressure profiles were fed to a computer running the Beatscope® software program (version 1.0; TNO-TPD Biomedical Instrumentation), implementing the Modelflow®model [Wesseling et al., 1993]. The pulse pressure profiles were analysed off-line to determine beat-by-beat systolic (Ps), diastolic (Pd) and mean (Pm) blood pressures. Beat-by-beat HR and SV were then calculated by using the procedure incorporated in the Beatscope®software. Beat-by-beat .
Q was then calculated as the product of SV times the corresponding HR.
2 P
ROTOCOLThe subjects were referred to the laboratory after a light meal consumed 2 h before. They were seated on the ergometer and the Portapres®cuffs were positioned. After the calibration procedures were completed, the mouthpiece and the nose-clip were placed in position and the acquisition of the gas fractions, flow and blood pressure signals was started. After 4 min rest, Q. C2H2 was measured. Then, the subject started pedalling against a 50 W workload at a constant pedalling rate of 60 revs · min-1. At the fifth minute of exercise, .
QC2H2 was measured again. At the end of the measurement, the subject immediately stopped and rested for 5 min. A new exercise run was then performed by increasing the workload by 50 W. Two additional exercise steps, separated by 5 min of rest, were performed up to the highest workload of 200 W.
3 C
ORRECTION OF .QMODELFLOW® WITH .
QC2H2 In order to correct the .
QModelflow®values by use of .
QC2H2, a workload was selected and, at the steady state, the average .
QModelflow®was calculated as the mean of beat-by-beat values over 1 min. A calibration factor was then calculated as the ratio of average .
QModelflow® to average Q. C2H2. The selected workload was 150 W, that is the workload at which this ratio showed the
lowest variability. The calibration factors were then used to recalculate average .
QModelflow®at rest and at all the remaining workloads.
4 S
TATISTICSCorrelation between variables was calculated by the least-squares method using the procedure of Brace [Brace, 1977]. Regression parameters were analysed by using the procedures for the comparison of regression lines of the first kind [Lentner, 1982]. The significance of differences between average values in the different workload conditions were evaluated by means of two-way ANOVA [Box et al., 1978]. Student’s t test for 1-sample analysis was utilized to reject the hypothesis zero. Agreement between the two methods of measurements was assessed by means of Bland-Altman analysis [Bland & Altman, 1986]. ANOVA for repeated measurements was applied to identify significant differences between averages related to the different workloads [Daniel, 1991].
5 R
ESULTS The average .QModelflow®and .
QC2H2 values are shown in Figure 12 as a function of the workload.
Linear regressions were calculated on the entire data for both variables (n=45;
Q. Modelflow®: y = 0.092x + 7.09 l.min-1, where [x] = 1 W ; (r=0.926, p<0.001) Q. C2H2 : y = 0.10x + 4.41 l.min-1, where [x] = 1 W ; (r=0.937, p<0.001).
The two lines had thus practically the same slope, but significantly different y-intercepts.
This means that .
QModelflow®was shifted upward with respect to .
QC2H2. The ratios between .
QModelflow®and .
QC2H2 at the different workloads are shown in Table 2.
These ratios varied with the workloads. The ratios at 100, 150 and 200 W were not significantly different from 1. The smallest S.D., and thus the smallest coefficient of variation (C.V = 100SD/Ratio), was found at 150 W. The average of all correction factors computed at all the workloads, including rest, was 0.87 ( ± 0.269).
Second study
Figure 13. Mean values of .
QModelflow® and .
QC2H2 plotted against workload
Table 2: Means, S.D. and coefficient of variation (C.V) of .
QC2H2 / .
QModelflow® ratios at rest and at the four workloads
Workload (W)
Q. C2H2 / .
QModelflow®
Ratio S.D C.V (%)
0 0.65 0.198 28.7
50 0.70 0.252 35.0
100 0.96 0.320 31.5
150 0.94 0.220 22.6
200 0.94 0.223 23.3
Figure 14. Relationship between .
QModelflow®, .
QC2H2 and .
QCorrected
(A) .
QModelflow® determined for each subject plotted against the corresponding Q. C2H2 values. (B) Difference between .
QC2H2 and .
QModelflow® values plotted against their mean. (C) .
QCorrected values determined in each subject plotted against the corresponding .
QC2H2 values. (D) Difference between .
QC2H2 and .
QCorrected
values plotted against their mean. In (A) and (C), the broken lines correspond to the lines of equality, and the solid lines are the regression lines. In (B) and (D), broken lines represent the 95 % limits of agreement.
Individual mean .
QModelflow®plotted as a function of the corresponding .
QC2H2 are shown in Figure 13(A). The linear relationship between these two parameters was y = 0.932x + 2.81 l.min-1 ; [x] = 1 l.min-1, indicating that the regression line was displaced upward with respect
Second study to the equality line (the line on which both sets of data would lie if they were identical). The
Q. Modelflow®values were significantly correlated with the .
QC2H2 values (r=0.784, p<0.01).
The results of the Bland–Altman analysis are shown in Figure 13(B). The bias (mean of the differences .
QModelflow®- .
QC2H2) was 1.83 litre · min-1. The bias value was significantly larger than 0, thus confirming that the regression line was displaced upward with respect to the equality line. The S.D. (precision) was 4.11 litre · min-1 and the 95% limits of agreement ranged from -6.23 to +9.89 l.min-1.
Corrected .
QModelflow®values ( .
QCorrected) at rest and at all workloads, except 150 W which was used to calculate the correction factors (see the Methods section), are plotted as a function of the corresponding .
QC2H2 in Figure 13(C). The regression equation was y =1.177x - 3.75 l.min-1, [x]=l.min-1. .
QCorrectedvalues were correlated significantly with .
QC2H2 values (r=0.931, p<0.01).
The results of the Bland–Altman analysis are shown in Figure 13(D). The bias (mean of the differencences .
QCorrected- .
QC2H2 ) was 0.24 litre·min-1and did not differ from 0. This indicated that the line relating .
QCorrectedand .
QC2H2 was equal to the equality line. S.D. (precision) was 3.48 litre · min-1and the 95% limits of agreement were at -6.58 and +7.05 min-1.
6 D
ISCUSSIONIn the present study, the hypothesis that, after appropriate correction with an independent method, Modelflow®provides reasonably accurate .
Q values was tested at rest and during exercise. To this end, .
Q values obtained non-invasively with Modelflow® were corrected using independently established .
Q values measured with an open-circuit acetylene technique.
The main result of the present study is that, after such a correction, Modelflow® applied to the arterial pulse pressure measured noninvasively on the finger provides a non-biased and reliable measure of .
Q in healthy subjects at rest and during exercise ranging from moderate to severe intensities. In contrast, uncorrected Modelflow® .
Q values ( .
QModelflow®) are significantly different from the corresponding .
QC2H2 values.
To our knowledge, the present study is the first in which .
QCorrectedvalues were compared with those measured with a respiratory method ( .
QC2H2 ) during high intensity exercise at steady state in humans. As such, the method offers a valid non-invasive approach for the assessment of .
Q on a beat-by-beat basis that is applicable not only at the exercise steady state, but also during exercise transients.
The results presented in Figures 12, 13(A) and 13(B), showing uncorrected .
QModelflow®values, are consistent with those obtained by others. Remmen [Remmen et al., 2002] compared Modelflow®applied to peripheral pulse pressure profiles with thermodilution and showed that Modelflow® did not yield accurate .
Q values in healthy elderly subjects at rest. Houtman [Houtman et al., 1999] showed that Modelflow®did not accurately predict .
Q during cycling exercise of moderate intensity compared with the CO2 rebreathing procedure. Taken together,
Q during cycling exercise of moderate intensity compared with the CO2 rebreathing procedure. Taken together,