Non‐invasive assessment of cardiac output during exercise in healthy young humans: comparison between Modelflow method and Doppler echocardiography method

Aims: The Modelflow method can estimate cardiac output from arterial blood pressure waveforms using a three‐element model of aortic input impedance (aortic characteristic impedance, arterial compliance, and systemic vascular resistance). We tested the reliability of a non‐invasive cardiac output estimation during submaximal exercise using the Modelflow method from finger arterial pressure waveforms collected by Portapres in healthy young humans. Methods: The Doppler echocardiography method was used as a reference method. Sixteen healthy young subjects (nine males and seven females) performed a multi‐stage cycle ergometer exercise at an intensity corresponding to 70, 90, 110 and 130% of their individual ventilatory threshold for 2 min each. The simultaneous estimation of cardiac output (15 s averaged data) using the Modelflow and Doppler echocardiography methods was performed at rest and during exercise. Results and Conclusion: The Modelflow‐estimated cardiac output correlated significantly with the simultaneous estimates by the Doppler method in all subjects (r = 0.87, P < 0.0001) and the SE of estimation was 1.93 L min^?1. Correlation coefficients in each subject ranged from 0.91 to 0.98. Although the Modelflow method overestimated cardiac output, the errors between two estimates were not significantly different among the exercise levels. These results suggest that the Modelflow method using Portapres could provide a reliable estimation of the relative change in cardiac output non‐invasively and continuously during submaximal exercise in healthy young humans, at least in terms of the relative changes in cardiac output.     

Noninvasive evaluation of cardiac output during postural change and exercise in humans: comparison between the modelflow and pulse dye-densitometry

To investigate whether the Model-flow method, by simulating the aortic input impedance model from a noninvasive monitoring of arterial blood pressure, reflected a reliable measure of cardiac output (CO) during postural change and whole-body exercise occurring in daily life, we compared the Modelflow-estimated CO with a simultaneous reference determined by the pulse dye-densitometry. Nine healthy volunteers performed postural change from supine to upright and dynamic stepping exercise. The Modelflow-estimated CO decreased to 4.8 +/- 0.5 l/min, from 5.8 +/- 0.6 l/min, during the postural change and increased to 12.8 +/- 1.3 l/min during a stepping exercise, returning to 5.1 +/- 0.4 l/min at 5 min after exercise. When comparing the pooled data of CO during resting and following exercise between the Modelflow and pulse dye-densitometry, we found that the average CO did not differ between the two estimates and that there was a significant correlation between them; the slope of the linear regression line corresponded to approximately 1.0. Although such linear relationship was also observed in an individual subject, the slope of the regression line varied from 0.737 to 1.588 among the subjects. The calibration of the Modelflow-estimated CO with the dye-densitometry value at supine or upright improved a correlation between the two estimates. Thus it is likely that the noninvasive Modelflow simulation from arterial blood pressure can provide a reliable estimation of group-average cardiac output during postural change and stepping exercise occurring in daily life. It will be recommended for a more accurate estimation of cardiac output in a given subject to calibrate the Modelflow data with an independent measure.     

Non-invasive cardiac output assessment during moderate exercise: pulse contour compared with CO2 rebreathing.

The arterial pulse contour method called Modelflow 2.1 calculates stroke volume continuously, beat to beat, from the non-invasive blood pressure signal measured by Finapres or Portapres. Portapres is the portable version of Finapres. The purpose of this study was to compare cardiac output (CO) calculated using Modelflow 2.1 (COmf) with CO obtained by the CO2 rebreathing method (COre) during steady state at moderate exercise levels. Twelve subjects visited the laboratory twice and performed submaximal exercise on a bicycle ergometer at 20%, 40% and 60% of their individual peak power output (POpeak). The averaged correlation between COmf and COre gives an r-value of 0.69, whereas the slope and intercept of the regression line were 1.06 and 1.65 respectively. The averaged difference between COmf and COre was 2.27 +/- 3.91 min-1 (mean +/- standard deviation). However, the test-retest difference between COmf and COre was 2.5 +/- 3.1 and 0.5 +/- 1.31 min-1 respectively. These results suggest that Modelflow 2.1 is not an accurate method for estimating CO from non-invasive blood pressure data collected by Portapres during exercise at up to 60% of the individual POpeak corresponding with daily life activity.     

Non-invasive pulsatile arterial pressure and stroke volume changes from the human finger

In this paper we review recent developments in the methodology of non-invasive finger arterial pressure measurement and the information about arterial flow that can be obtained from it. Continuous measurement of finger pressure based on the volume-clamp method was introduced in the early 1980s both for research purposes and for clinical medicine. Finger pressure tracks intra-arterial pressure but the pressure waves may differ systematically both in shape and magnitude. Such bias can, at least partly, be circumvented by reconstruction of brachial pressure from finger pressure by using a general inverse anti-resonance model correcting for the difference in pressure waveforms and an individual forearm cuff calibration. The Modelflow method as implemented in the Finometer computes an aortic flow waveform from peripheral arterial pressure by simulating a non-linear three-element model of the aortic input impedance. The methodology tracks fast changes in stroke volume (SV) during various experimental protocols including postural stress and exercise. If absolute values are required, calibration against a gold standard is needed. Otherwise, Modelflow-measured SV is expressed as change from control with the same precision in tracking. Beat-to-beat information on arterial flow offers important and clinically relevant information on the circulation beyond what can be detected by arterial pressure.     

Estimation of arterial compliance in aortic regurgitation: three methods evaluated in pigs

Three methods for measuring arterial compliance when aortic regurgitation is present are examined. The first two methods are based on a Windkessel model composed of two elements, compliance C and resistance R. Arterial compliance was estimated from diastolic pressure waveforms and diastolic regurgitant flow for one method, and from systolic aortic pressure waveforms and systolic flow for the other method. The third method was based on a three-element Windkessel model, composed of characteristic resistance r, compliance C and resistance R. In this method arterial compliance was calculated by adjusting the model to the modulus and phase of the first harmonic term of the aortic input impedance. The three methods were compared and validated in six anaesthetised pigs over a broad range of aortic pressures. The three methods were found to give quantitatively similar estimates of arterial compliance at mean aortic pressures above 60 mm Hg. Below 60 mm Hg, estimates of arterial compliance varied widely, probably because of poor validity of the Windkessel models in the low pressure range.     

Baroreflex-Mediated Changes in Cardiac Output and Vascular Conductance in Response to Alterations in Carotid Sinus Pressure during Exercise in Humans

We sought to quantify the contribution of cardiac output ( Q ) and total vascular conductance (TVC) to carotid baroreflex (CBR)-mediated changes in mean arterial pressure (MAP) during mild to heavy exercise. CBR function was determined in eight subjects (25 ± 1 years) at rest and during three cycle exercise trials at heart rates (HRs) of 90, 120 and 150 beats min⁻¹ performed in random order. Acute changes in carotid sinus transmural pressure were evoked using 5 s pulses of neck pressure (NP) and neck suction (NS) from +40 to −80 Torr (+5.33 to −10.67 kPa). Beat-to-beat changes in HR and MAP were recorded throughout. In addition, stroke volume (SV) was estimated using the Modelflow method, which incorporates a non-linear, three-element model of the aortic input impedance to compute an aortic flow waveform from the arterial pressure wave. The application of NP and NS did not cause any significant changes in SV either at rest or during exercise. Thus, CBR-mediated alterations in Q were solely due to reflex changes in HR. In fact, a decrease in the carotid-HR response range from 26 ± 7 beats min⁻¹ at rest to 7 ± 1 beats min⁻¹ during heavy exercise (   P = 0.001  ) reduced the contribution of Q to the CBR-mediated change in MAP. More importantly, at the time of the peak MAP response, the contribution of TVC to the CBR-mediated change in MAP was increased from 74 ± 14 % at rest to 118 ± 6 % (   P = 0.017  ) during heavy exercise. Collectively, these findings indicate that alterations in vasomotion are the primary means by which the CBR regulates blood pressure during mild to heavy exercise.     

Noninvasive ambulatory assessment of cardiac function in healthy men exposed to carbon monoxide during upper and lower body exercise

Very little is known about the cardiovascular responses of exercising individuals when exposed to carbon monoxide (CO). Sixteen healthy nonsmoking men aged 18–29 years participated in the study. Using a combination of exposures to CO by breathing from a bag or in an environmental chamber, subjects performed a randomized sequence of brief (5 min) multi-level treadmill and hand-crank exercises on different days at less than 2% carboxyhemoglobin (COHb) and after attaining target levels of 5%, 10%, 15%, and 20% COHb. To assess cardiac function changes we employed noninvasive impedance cardiography (ICG) and three-lead electrocardiograms (ECG). The ICG was used to estimate cardiac output, stroke volume, heart rate, cardiac contractility, and time-to-peak ejection time. The ECG was used to assess myocardial irritability and ischemia, and changes in cardiac rhythm. The results showed that the cardiovascular system compensated for the reduced O₂-carrying capacity of the blood by augmenting heart rate, cardiac contractility, and cardiac output for both upper-body and lower-body exercise. While this mechanism served well in submaximal exercise, the enhanced cardiovascular response to exercise was not without physiological costs because it began to fail at moderate levels of CO exposure and exercise. We concluded that young, apparently healthy men can perform submaximal upper and lower-body exercise without overt impairment of cardiovascular function after CO exposures attaining 20% COHb. Accepted: 6 June 2000     

Beat-to-beat noninvasive stroke volume from arterial pressure and Doppler ultrasound

The proper understanding of the cardiovascular mechanisms involved in complaints of short-lasting dizziness and the evaluation of unexplained recurrent syncope requires continuous monitoring of cardiac stroke volume (SV) in addition to blood pressure and heart rate. The primary aim of the present study was to evaluate a pulse wave analysis method that calculates beat-to-beat flow from non-invasive arterial pressure by simulating a non-linear, time-varying model of human aortic input impedance (Modelflow; MF), by comparing MF stroke volume (SV_MF) to Doppler ultrasound (US) flow velocity SV (SV_US). A second purpose was to compare the two methods under two different conditions: the supine and head-up tilt (30°) position. SV_US and SV_MF with non-invasive arterial pressure (Finapres) as input to the aortic model were measured beat-to-beat during spontaneous supine breathing and in the passive 30° head-up tilt (HUT30) position in six normotensive healthy humans [three females, mean age 24 (21–26) years]. There were variations in supine SV track between the two methods with zero difference and a SD of the beat-to-beat difference (MF–US) of 4.2%. HUT30 induced a systematic difference of 10.5% and an increase in SD to 6.9%, which was reproducible. Beat-to-beat changes in SV in the supine resting condition were equally well assessed by both methods. Systematic differences appear during HUT30 and show opposite signs. The difference between the two methods upon a change in body position may be attributed to limitations in each method.     

Left ventricular volumes during exercise in endurance athletes assessed by contrast echocardiography

AIM: The objective was to assess left ventricular (LV) volumes at rest and during upright submaximal exercise in endurance athletes to see whether changes in heart volume could explain the large predicted increase in cardiac output in endurance athletes. METHOD: Contrast echocardiography was used to assess changes in LV volumes during upright bicycle exercise in 24 healthy male endurance athletes. Maximal oxygen uptake and oxygen pulse were measured by using cardiopulmonary exercise testing. RESULTS: From rest to exercise at a heart rate of 160 beats min(-1) end-diastolic volume increased by 18% (P < 0.001) and end-systolic volume decreased by 21% (P = 0.002). Stroke volume showed an almost linear increase during exercise (45% increase, P < 0.001). The increase in end-diastolic volume contributed to 73% of the increase in stroke volume. No significant differences were observed between stroke volume calculated from LV volumes with contrast echocardiography and stroke volume calculated from oxygen pulse at heart rates of 130 and 160 beats min(-1). Using the linear regression equation between oxygen uptake and cardiac output assessed by echocardiography during exercise (r=0.87, P=0.002), cardiac output at maximal exercise was estimated at 33 +/- 3 L min(-1), with an estimated increase in stroke volume by 69% from rest to maximal exercise. CONCLUSION: By using contrast echocardiography, a large increase in stroke volume in endurance athletes could be explained by an almost linear increase in end-diastolic volume and an initial small decrease in end-systolic volume during incremental upright exercise.     

Arterial windkessel parameter estimation: A new time-domain method

We developed and validated a new, more accurate, and easily applied method for calculating the parameters of the three-element Windkessel to quantitate arterial properties and to investigate ventriculoarterial coupling. This method is based on integrating the governing differential equation of the three-element Windkessel and solving for arterial compliance. It accounts for the interaction between characteristic impedance and compliance, an important phenomenon that has been ignored by previously implemented methods. The new integral method was compared with four previously published methods as well as a new independent linear least-squares analysis, using ascending aortic micromanometric and volumetric flow measurements from eight dogs. The parameters calculated by the new integral method were found to be significantly different from those obtained by the previous methods but did not differ significantly from maximum likelihood estimators obtained by a linear leastsquares approach. To assess the accuracy of parameter estimation, pressure and flow waveforms were reconstructed in the time domain by numerically solving the governing differential equation of the three-element Windkessel model. Standard deviations of reconstructed waveforms from the experimental ensemble-averaged waveforms, which solely reflect the relative accuracy of the Windkessel parameters given by the various methods, were calculated. The new integral method invariably yielded the smallest error. These results demonstrate the improved accuracy of our new integral method in estimating arterial parameters of the three-element Windkessel.     

Reproducibility of the alterations in circulation and cerebral oxygenation from supine rest to head-up tilt.

Cardiovascular stability, as affected by several diseases, may be assessed by head-up tilt testing. Follow-up studies are essential in both evaluating interventions and assessing progression. However, data on the reproducibility of the changes in circulatory status and cerebral oxygenation provoked by head-up tilt testing are fundamental to follow-up studies. The aim of this study was, therefore, to assess the reproducibility of the alterations in stroke volume (SV), mean arterial pressure (MAP), as well as oxygenated ([O2Hb]) and deoxygenated haemoglobin ([HHb]) concentration in cerebral tissue from supine rest (SUP) to head-up tilt (HUT). SV was calculated by Modelflow, a pulse contour method, from the finger arterial pressure wave measured by Portapres, the portable version of Finapres. [O2Hb] and [HHb] were measured using near-infrared spectroscopy (NIRS). Ten healthy individuals visited the laboratory on two different days. On both days, they underwent 10 min SUP followed by 10 min 70 degrees HUT twice. SV decreased, which was (in part) compensated for by an increased heart rate, while MAP increased slightly during HUT compared with SUP. Although [HHb] increased during HUT, no presyncope symptoms were experienced. The circulatory variables (SV, HR and MAP) as well as [HHb] showed an acceptably small systematic and random error as well as reproducibility error compared with the observed difference between HUT and SUP and were similar between and within visits. Therefore, it is concluded that MAP measured by Portapres and SV calculated by Modelflow as well as HHb measured by NIRS seem to be reproducible and may therefore be used in follow-up studies.     

Coronary circulation in acute hypoxia

Healthy young men were subjected to different degrees of hypoxia at rest and during increased levels of cardiac work induced by atrial pacing and physical exercise at submaximal and maximal loads. Coronary sinus (cs) blood flow was measured by thermodilution and a-cs differences of O2 and lactate were obtained. At low cardiac power output (rest, pacing) the reduction in arterial oxygen content was compensated for mainly by a more complete myocardial oxygen extraction producing lowered cs O2 saturation and tension, while at higher cardiac power (exercise) the compensatory mechanism was entirely an increased coronary blood flow. It was possible to compensate fully for a reduction in arterial O2 saturation of 9% even during maximal physical exercise. With a reduction in arterial oxygen content of more than 20-25% the flow increase was sufficient to supply the heart with enough O2 during submaximal (heart rate 157 beats min-1) but not maximal exercise, in which case anaerobic glycolysis contributed significantly to the myocardial energy metabolism. It is concluded that the normal heart has a 'coronary flow reserve' of about 33% above the flow prevailing during maximal physical exercise under air breathing.     

Socioeconomic status and hemodynamic recovery from mental stress

We assessed the changes in cardiac index and total peripheral resistance underlying blood pressure reactions and recovery from acute mental stress, in relation to socioeconomic status. A sample of 200 men and women aged 47-59 years was divided on the basis of occupation into higher, intermediate, and lower socioeconomic status groups. Blood pressure was monitored using the Portapres, and hemodynamic measures were derived by Modelflow processing of the arterial pressure waveform. Blood pressure increases during two stressful behavioral tasks were sustained by increases in cardiac index and total peripheral resistance. During the 45-min posttask recovery period, cardiac index fell below baseline levels, whereas peripheral resistance remained elevated. Peripheral resistance changes during recovery varied with socioeconomic status and blood pressure stress reactivity, with particularly high levels in reactive low status participants. Results are consistent with the hypothesis that disturbances of stress-related autonomic processes are relevant to the social gradient in cardiovascular disease risk.     

Fast Estimation of Arterial Vascular Parameters for Transient and Steady Beats with Application to Hemodynamic State under Variant Gravitational Conditions

Numerous parameter estimation techniques exist for characterizing the arterial system using electrical circuit analogs. These techniques are often limited by requiring steady-state beat conditions and can be computationally expensive. Therefore, a new method was developed to estimate arterial parameters during steady and transient beat conditions. A four-element electrical analog circuit was used to model the arterial system. The input impedance equations for this model were derived and reduced to their real and imaginary components. Next, the physiological input impedance was calculated by computing fast Fourier transforms of physiological aortic pressure (AoP) and aortic flow. The approach was to reduce the error between the calculated model impedance and the physiological arterial impedance using a Jacobian matrix technique which iteratively adjusted arterial parameter values. This technique also included algorithms for estimating physiological arterial parameters for nonsteady physiological AoP beats. The method was insensitive to initial parameter estimates and to small errors in the physiological impedance coefficients. When the estimation technique was applied to in vivo data containing steady and transient beats it reliably estimated Windkessel arterial parameters under a wide range of physiological conditions. Further, this method appears to be more computationally efficient compared to time-domain approaches. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8710+e, 0230Qy     

Continuous Left Ventricular Ejection Fraction Monitoring by Aortic Pressure Waveform Analysis

We developed a technique to monitor left ventricular ejection fraction (EF) by model-based analysis of the aortic pressure waveform. First, the aortic pressure waveform is represented with a lumped parameter circulatory model. Then, the model is fitted to each beat of the waveform to estimate its lumped parameters to within a constant scale factor equal to the arterial compliance (C _a). Finally, the proportional parameter estimates are utilized to compute beat-to-beat absolute EF by cancelation of the C _a scale factor. In this way, in contrast to conventional imaging, EF may be continuously monitored without any ventricular geometry assumptions. Moreover, with the proportional parameter estimates, relative changes in beat-to-beat left ventricular end-diastolic volume (EDV), cardiac output (CO), and maximum left ventricular elastance (E _max) may also be monitored. To evaluate the technique, we measured aortic pressure waveforms, reference EF and EDV via standard echocardiography, and other cardiovascular variables from six dogs during various pharmacological influences and total intravascular volume changes. Our results showed overall EF and calibrated EDV root-mean-squared-errors of 5.6% and 4.1 mL, and reliable estimation of relative E _max and beat-to-beat CO changes. These results demonstrate, perhaps for the first time, the feasibility of estimating EF from only a blood pressure waveform.     

Improved method for cardiac output determination in man using ultrasound Doppler technique

An existing ultrasound Doppler method for measuring cardiac output has been improved and refined, partly by locating the sampling volume higher up in the aorta while still using the aortic ring size as the effective transverse flow area. The basis for using this technique is the approximately rectangular systolic velocity profile in the aortic orifice in physiologically and anatomically normal subjects, and the fact that this profile velocity is conserved as the maximum velocity in the ascending aorta for some 3 to 4 cm above the valves. This higher location of the sampling volume improves Doppler signal quality, and does not reduce the accuracy of the method, as can be confirmed in each experimental subject. Together with automatic computer-based online signal analysis, the technique employed enables us to make continuous long-term beat-to-beat measurements of cardiac output in subjects without aortic valve disease or grossly deforming disease of the aortic root.     

Effects of chronic dobutamine administration on the response to acute exercise in dogs

The effects of chronic dobutamine administration on haemodynamic and metabolic responses to submaximal and maximal exercise were studied in dogs. Dobutamine was infused at a rate of 40 micrograms/kg min-1, 2 h day-1, 5 days week-1 for a period of 6 weeks. Acute infusion of dobutamine for 1 h increased heart rate by 73 +/- 30 beats min-1 and cardiac output by 143 +/- 141 ml/min kg-1, reduced mean arterial blood pressure by 12 +/- 10 mmHg and arterial-venous O2 difference by 1.5 +/- 1 vol%. Maximal oxygen consumption, heart rate, stroke volume, cardiac output and arterial-venous O2 difference were unchanged after 6 weeks of treatment. Reductions in heart rate at rest and during submaximal exercise following chronic dobutamine treatment were small and significant only at the lowest exercise level studied. Mixed venous lactate concentrations measured at rest, during submaximal and maximal exercise and at 2 min of recovery were not different after dobutamine treatment. Chronic dobutamine infusion did not change the citrate synthase activity in the lateral gastrocnemius muscle. These results suggest that chronic dobutamine therapy in healthy dogs does not produce aerobic training responses.     

Effect of increased blood fluidity through hemodilution on general circulation at rest and during exercise in dogs

During progressive normovolemic hemodilution with dextran-60, circulatory functions (cardiac output, oxygen delivery to tissues, arterial pressure and mixed venous oxygen saturation) and total body oxygen consumption were studied in conscious dogs at rest and during two levels of submaximal treadmill exercise. At rest, cardiac output rose continuously with progressive hemodilution. This increase, however, was not sufficient to compensate for the reduced arterial oxygen content. Consequently oxygen delivery fell significantly from 23.3 +/- 1.8 ml/min with kg at hematocrit 47.5% to 15.7 +/- 0.9 ml/min with kg at hematocrit 12.5%. The constant oxygen consumption was maintained by a simultaneous increase in oxygen extraction from blood. During the superimposed stress of exercise, a constant oxygen consumption was maintained between hematocrit ranges of 50 to 15 or 25%, respectively. Again, the increase of cardiac output due to hemodilution did not compensate for the reduced arterial oxygen content and consequently oxygen extraction rate was increased. These data demonstrate that at rest (and even more during submaximal treadmill exercise) the reduced whole blood viscosity or improved fluidity during hemodilution does not initiate an increase in cardiac output that is sufficient to maintain a constant oxygen delivery to the tissues.     

Priority of blood flow to splanchnic organs in humans during pre- and post-meal exercise

Cardiac output and superior mesenteric arterial flow in five healthy young men were followed using Doppler ultrasound techniques at rest and during 4 min bouts of bicycle exercise in both a pre- and a post-meal situation. The meal given was mixed and heavy, with an energy content (related to body size) of about 1400–1600 kcal (5.9-6.9 MJ). Two levels of exercise, 50–65 W and 150–200 W (about 75% of Vo_tmax), were tested, with the subjects cycling in a reclining position. Superior mesenteric arterial flow increased threefold, to about 1.11 min^-1, after the meal. During exercise in the fasting situation there were only modest changes in splanchnic vascular conductance, and moderate increases in superior mesenteric arterial flow were actually recorded. Exercise in the post-prandial state caused appreciable reductions in splanchnic vascular conductance, and a 38% reduction was observed during the most heavy exercise. However, not even such a decrease in conductance resulted in any definite reduction in superior mesenteric arterial blood flow, which was maintained at the pre-exercise level. Cardiac output increased by about 1.3 1 min^-1 after the meal. The exercise-induced increases in cardiac output were of the same order in the fasting and in the post-prandial state. Variance analyses showed the high cardiac output levels reached during postprandial exercise to be no different from levels that would be reached by pure summation of the changes caused by eating alone and by exercise alone. It is concluded that blood flow to the splanchnic organs in reclining man retains its high pre- and post-prandial priority during short exercise bouts of up to 75% of Vo_Smax.     

Metabolically exaggerated cardiac reactions to acute psychological stress revisited

The reactivity hypothesis postulates that large magnitude cardiovascular reactions to psychological stress contribute to the development of pathology. A key but little tested assumption is that such reactions are metabolically exaggerated. Cardiac activity, using Doppler echocardiography, and oxygen consumption, using mass spectrometry, were measured at rest and during and after a mental stress task and during graded submaximal cycling exercise. Cardiac activity and oxygen consumption showed the expected orderly association during exercise. However, during stress, large increases in cardiac activity were observed in the context of modest rises in energy expenditure; observed cardiac activity during stress substantially exceeded that predicted on the basis of contemporary levels of oxygen consumption. Thus, psychological stress can provoke increases in cardiac activity difficult to account for in terms of the metabolic demands of the stress task.