From the department of Cardiothoracic and also Vascular surgical procedure (V.E.H., E.S., O.K.), grandfather Center, academy of speculative Clinical study (T.F., E.M.P.), and Department that Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus college Hospital, Aarhus, Denmark.
K. Emmertsen

From the department of Cardiothoracic and also Vascular surgical treatment (V.E.H., E.S., O.K.), grandfather Center, academy of experimental Clinical research study (T.F., E.M.P.), and Department the Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus college Hospital, Aarhus, Denmark.
E. Stenbøg

From the room of Cardiothoracic and also Vascular surgical treatment (V.E.H., E.S., O.K.), grandfather Center, academy of experimental Clinical research (T.F., E.M.P.), and also Department the Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus college Hospital, Aarhus, Denmark.
T. Fründ

From the department of Cardiothoracic and Vascular surgical treatment (V.E.H., E.S., O.K.), mr Center, institute of experimental Clinical study (T.F., E.M.P.), and also Department that Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus university Hospital, Aarhus, Denmark.
M. Rahbek Schmidt

From the room of Cardiothoracic and Vascular surgical procedure (V.E.H., E.S., O.K.), grandfather Center, academy of speculative Clinical research (T.F., E.M.P.), and Department the Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus university Hospital, Aarhus, Denmark.
O. Kromann

From the room of Cardiothoracic and Vascular surgical procedure (V.E.H., E.S., O.K.), mr Center, academy of experimental Clinical research (T.F., E.M.P.), and Department that Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus college Hospital, Aarhus, Denmark.
K. Sørensen

From the room of Cardiothoracic and Vascular surgery (V.E.H., E.S., O.K.), mr Center, academy of speculative Clinical research study (T.F., E.M.P.), and Department the Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus college Hospital, Aarhus, Denmark.
E.M. Pedersen

From the room of Cardiothoracic and also Vascular surgery (V.E.H., E.S., O.K.), mr Center, academy of speculative Clinical study (T.F., E.M.P.), and Department the Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus college Hospital, Aarhus, Denmark.

Background— small is known about blood flow and its partnership to respiration during exercise in patient with complete cavopulmonary link (TCPC).

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Methods and Results— us studied 11 patient 12.4±4.6 years (mean±SD) of period 5.9±2.8 years (mean±SD) ~ TCPC operation. Real-time MRI was used to measure up blood flow in the premium vena cava (SVC), worse vena cava (IVC), and ascending aorta under inspiration and also expiration during supine lower-limb exercise (rest, 0.5 and 1.0 W/kg) on one ergometer bicycle. IVC and also aortic circulation increased from 1.60±0.52 and 2.99±0.83 L/min every m2 at rest to 2.58±0.71 and also 3.97±1.20 L/min per m2 in ~ 0.5 W/kg and also to 3.25±1.23 and 4.62±1.49 L/min every m2 in ~ 1.0 W/kg (P≤0.05). SVC circulation remained unchanged. Resting circulation in the IVC was greater throughout inspiration (2.99±1.25 L/min per m2) than during expiration (0.83±0.44 L/min per m2) (inspiratory/mean flow ratio, 1.9±0.5), and also retrograde flow was current during expiration (11±12% of average flow). The advantage of inspiratory flow in IVC decreased with exercise to an inspiratory/mean flow ratio the 1.5±0.2 (P≤0.05) and also 1.4±0.3 in ~ 0.5 and also 1.0 W/kg, respectively.

Conclusions— In the TCPC, circulation IVC and aortic yet not SVC flows increase with supine foot exercise. Inspiration facilitates IVC circulation at rest but less so during exercise, as soon as the peripheral pump appears to be an ext important.


Total cavopulmonary connection (TCPC) is a palliative operation used in patient with complex cardiac malformations that preclude a biventricular repair. The an essential physiology of the TCPC circulation is a dissociation that the venous return from a ventricular strength source.

We previously used MRI to research flow throughout breath hold in the TCPC circulation. At rest, the pulmonary and also caval circulation was defined by biphasic flow and also pressure waveforms v maxima in atrial systole and also late ventricular systole.1 with supine bicycle exercise, blood circulation increased, generally attributable to an increase in heart rate and also only contempt attributable come an boosted stroke volume.2

Breathing has a pronounced effect on flow rates in the Fontan circulation in ~ rest,3–7 leading to a concept of a respiratory tract pump that suck blood into the lungs during inspiration.8 However, it is mainly unknown exactly how breathing affect flow throughout exercise.

The target of the existing investigation to be to study the influence of breathing on real-time antegrade and also retrograde flow in the caval veins and also in the aorta during exercise in patients v TCPC.


Methods


Study Group

Eleven patient (age, 12.4±4.6 year ) to be studied 5.9±2.8 year after TCPC (Table 1). The operation had included an end-to-side anastomosis in between the exceptional vena cava (SVC) and also the ideal pulmonary artery and an extracardiac (n=1) or intraatrial (n=10) prosthetic baffle connecting the inferior vena cava (IVC) with the inferior surface ar of the appropriate pulmonary artery or the pulmonary key trunk.
TABLE 1. Patience Characteristics

Values are median (SD).
Age, y12.4 (4.6)
Sex, male/female5/6
Age at surgery, y6.5 (3.5)
Time because surgery, y5.9 (2.8)
Weight, kg37 (18)
Height, cm142 (21)
Diagnosis, n
Tricuspid atresia7
Double-inlet left ventricle3
Mitral atresia1

All patients to be in new York heart Association functional class I come II, in sinus rhythm, and without clinical indicators of congestive love failure. Echocardiography performed in ~ 3 months of the study showed an excellent ventricular duty and lack of aortic valve incompetence. Cardiac catheterization had been carry out 3.2±1.9 years before the study and also disclosed unobstructed pathways.

Four patients had actually minute job defects. One patient had actually a left-sided SVC draining come the coronary sinus. All patients had actually resting arterial oxygen saturations >95%.

Informed consent under a protocol authorized by the Danish Research moral Committee was acquired from all subjects or their parents.


Study Design

Patients were investigated throughout rest and exercise in ~ 2 various workload levels. Lock were placed supine in the MRI scanner v their feet strapped in the pedals of an ergometer bicycle mounted on the scanner table (MRI cardiac ergometer, Lode BV). Heart price was monitored by a traditional ECG-monitoring system and also by pulse oxymetry (Nonin 8600 FO). Inspiration and expiration were monitored with an air-filled belt an installed on the abdomen and also connected by a 2-m-long air tube to a pressure transducer.


Magnetic Resonance Imaging

MRI to be performed utilizing a Philips NT 1.5 Tesla whole-body scanner equipped through 21- and also 105-mT/m every ms gradients and also CPR6 research software and also using an 18-cm recipient coil.

Standard scout photos of the heart and great vessels were obtained in 3 orthogonal planes. Native the reconnaissance images, double angulated flow measurement planes to be planned orthogonally come the SVC, IVC, and ascending aorta. In the SVC, flow was measured immediately above the pulmonary anastomosis. Circulation in the IVC was measured in ~ the level the the lateral tunnel, over the coronary sinus. Aortic circulation was measure up in the ascending aorta.

Real-time flow measurements were performed in random order in the IVC, SVC, and also aorta at rest and during exercise. Every measurement consisted of 120 consecutive, real-time (no ECG triggering) phase-contrast flow acquisitions, every lasting 48 come 56 ms, giving a structure rate of about 20 frames per second.

A segmented gradient-echo phase contrast (echo planar imaging technique) through a field of watch of 90×136 mm and 26×64 matrix (pixel size, 3.4×2.1 mm2, reconstructed to 1.1×1.1 mm2), 5- to 7-mm slice thickness, 13 readouts, 0.8 half-scan factor, echo time 4 to 5 ms, and also repetition time 12 come 13 ms to be used. Velocity encoding differed from 50 come 120 cm/s depending upon vessel and exercise level.

ECG and also respiratory waveforms were synchronized through each flow measurement and saved for later analysis. Hand-operated segmentation that vessels was performed using committed software and volume flow for each of the 120 measurements calculated (Figure).

*

Volume circulation data indigenous 1 patience synchronized come ECG and respiratory signal because that both aorta, IVC and SVC at remainder (left), and also at 1 W/kg exercise (right). Values for every 120 real-time measurements are presented as a function of time for each series. Through exercise, the ECG signal became increasingly distorted.

For each flow measurement, 2 to 4 respiratory cycles v 6.5 to 10 cardiac cycles were obtained. The air-filled device for respiratory tract measurement offered a delay of about 500 ms in between the respiratory motion of the patient and the appearance of the respiratory signal. All respiratory curves were corrected 500 ms backwards accordingly.

The start of the inspiratory phase was collection to the begin of the increase deflection and the start of expiration to the start of the bottom deflection of the respiratory tract signal.


Exercise Protocol

Resting circulation measurements to be performed with the feet in the pedals, positioned between 4 and also 22 cm over the scanner table. Hereafter, the patient performed consistent leg exercise at workloads that 0.5 and 1.0 W/kg. At each workload, practice was ongoing until the heart price was secure for 2 minutes. Flow measurements were climate performed if the patient was still exercising. If exercise caused misplacement of the measure plane, a real-time reconnaissance lasting 15 seconds was obtained, and the slice was repositioned and the circulation measurement repeated.


Calculations

Heart and also respiratory prices at each occupational level were calculated as the average values over the time during which flow measurements to be performed in the 3 different measurement positions. Blood flow and stroke volume were measured because that 2 respiratory cycles. The start and the finish of the 2 inspiratory and also expiratory phases were figured out from the respiratory tract waveforms. The size of the inspiratory phase loved one to the totality respiratory bicycle (inspiratory fraction) to be calculated. The mean circulation rate indigenous 2 inspiratory and also from 2 expiratory phases, respectively, to be computed, and overall median flow. Inspiratory flow rates loved one to mean flow rates during a full respiratory bike (inspiratory circulation fraction) were calculated. When periods that retrograde blood circulation were found, the percentage of the retrograde flow relative to the average forward flow was calculated. Circulation rates to be indexed to body surface ar area and expressed as liter per minute every square meter.


Statistical Analysis

All variables are expressed as mean±SD. Variables measured at practice levels were contrasted with resting values by the usage of 2-tailed, combine Student’s t test.

The aortic and also caval flow values were contrasted in inspiration and expiration, and also the retrograde flow percentage to be compared in between exercise levels making use of 2-tailed paired t test. P≤0.05 was considered significant.


Results

All patient completed the protocol. The love rate and respiratory rate boosted with raising levels of exercise (PTable 2). The inspiratory fraction increased indigenous the relaxing state to the exercise level of 0.5 W/kg (PTABLE 2. Love Rate, respiratory tract Rate, and also Duration the Inspiratory Phase relative to the whole Respiratory cycle (Inspiratory Fraction) throughout Flow measurements at Rest and also During Exercise

Heart Rate, min−1Respiratory Rate, min−1Inspiratory FractionData space mean±SD.*P≤0.05 contrasted with previous practice level.Rest74 ±1421 ±40.35 ±0.050.5 W/kg90 ±11*30 ±7*0.41 ±0.04*1.0 W/kg104 ±8*35 ±8*0.41 ±0.04
Flows and Respiratory Influence

Table 3 shows circulation rates for the research group and also the influence of respiration. Typical aortic and IVC flow rates increased substantially with enhancing exercise, whereas SVC flow rates to be unchanged. Aortic circulation rates were slightly reduced (PTABLE 3. Median Blood circulation Rates (L/min every m2) in 2 respiratory tract Cycles and the corresponding Mean circulation Rates during Inspiration and also Expiration in the Aorta, IVC, and also SVC in ~ Rest and at 2 different Exercise Levels

AortaIVCSVCData room mean±SD of measurements in the 11 patients. Inspiratory circulation rates family member to mean flow rates in a full respiratory bicycle (inspiratory circulation fraction) are offered for every vessel in ~ each practice level. NS shows no significant difference compared with flow rate at previous practice level.*Significant (P≤0.05) difference contrasted with circulation rate in ~ previous exercise level.†Significant (P≤0.05) difference between inspiratory and also expiratory circulation rates.Rest circulation in respiratory tract cycle2.99±0.831.60±0.521.26±0.34 circulation in inspiration2.85±0.732.99±1.251.26±0.32 circulation in expiration3.24±0.91†0.83±0.44†1.29±0.42 Inspiratory flow fraction1.0±0.11.9±0.51.0±0.20.5 W/kg flow in respiratory cycle3.97±1.20*2.58±0.71*1.27±0.42 (NS) circulation in inspiration3.84±1.243.86±1.291.37±0.56 flow in expiration4.33±1.481.79±0.65†1.21±0.39 Inspiratory circulation fraction1.0±0.1 (NS)1.5±0.2*1.1±0.3 (NS)1.0 W/kg circulation in respiratory tract cycle4.62±1.49*3.25±1.23*1.27±0.46 (NS) flow in inspiration4.31±1.574.63±2.041.23±0.47 flow in expiration4.88±1.502.39±1.15†1.36±0.57 Inspiratory circulation fraction0.9±0.1 (NS)1.4±0.3 (NS)1.0±0.3 (NS)

Inspiratory stroke volumes were 46.3±12.8 mL/m2 in ~ rest and 47.4±13.2 and also 48.2±15.6 mL/m2 in ~ the 2 exercise levels, respectively. The matching expiratory stroke volumes were 49.0±13.2, 50±14.7, and 50.7±16.1 mL/m2, respectively. This slight rise in stroke volume v exercise was not statistically significant.

Figure 2 reflects blood flow from 1 patient in relation to the respiratory and also cardiac cycle at rest and also during practice at 1.0 W/kg. Aortic circulation rate at remainder varied mostly in the cardiac cycle through a little retrograde flow during diastole and showed virtually no variation v respiration. During exercise, flow rate enhanced slightly during expiration. Resting IVC circulation showed marked respiratory variation, v the highest flow rate occurring during inspiration. Throughout exercise, the circulation rate increased and the respiratory tract fluctuation was still present. SVC circulation at rest and also during exercise boosted slightly with inspiration but varied less with respiration 보다 IVC flow.


Correlation in between Aortic circulation Rates and Systemic Venous circulation Rates

The average aortic flow rate differed much less than 6% native the combined SVC and also IVC circulation rates. However, once looking individually at the inspiratory and also expiratory phases, huge variations in blood flow were found. In ~ rest, the linked venous circulation rate was 51% greater than the aortic flow throughout inspiration (PPPPRetrograde Flow

Retrograde circulation accounted for 2% to 3% of average blood circulation in the ascending aorta and also 0% to 1% in the SVC, with no changes with exercise. Retrograde blood in IVC diminished from 10.5±12.4% of median blood circulation at rest to 2.9±4.0% throughout exercise (PFlow throughout Rest

The current study confirmed that resting IVC flow has marked respiratory variability in the TCPC circulation.5,7 The effects of breathing to be dual, with inspiratory facilitation and expiratory inhibition the the lower body venous return, in some patients leading to expiratory IVC flow reversal. Inspiratory augmentation of pulmonary blood flow after a classic atriopulmonary anastomosis3,6 or a full cavopulmonary anastomosis4,9,10 has previously been described.

The sports in intrathoracic pressure during breathing room theoretically equally distributed to the IVC and also SVC, but only IVC flow was influenced. This distinction in caval flow variation with respiration was more than likely attributable to a higher venous capacitance in the lower body half, allowing for blood buildup in the veins the the reduced body fifty percent during expiration and also mobilization the this pool during inspiration.

The current finding that a combined venous flow rate exceeding aortic flow rate by 51% throughout inspiration and also being 34% lower during expiration shows that in ~ the same respiratory cycle, the pulmonary circulation acts as a reservoir with a big inspiratory capacity. This may an outcome in reduced left ventricular filling pressure throughout inspiration and thus describe why aortic circulation rates to be lower throughout inspiration. There is no previous description of this phenomenon in TCPC-operated patients, but a 10% decrease in aortic flow during inspiration has actually been discovered in healthy and balanced patients.11 our finding of a little retrograde flow in the ascending aorta is a common phenomenon related to valve closure and coronary perfusion.


Flow during Exercise

This is the first quantitative research of MR-measured real-time volume flow in TCPC-operated patients during exercise. Aortic and also IVC flows increased with greater levels the supine bicycling conversely, SVC flows continued to be unchanged, reflecting that the work lots were brought predominantly through the muscle of the reduced body half. The absolute circulation values and also the rise in circulation are equivalent to what has actually been explained using respiratory mass spectrometry.8

To describe the complicated hemodynamic alters during exercise, the ideas of a cardiac pump, a respiratory tract pump, and also a peripheral pump have actually been introduced.12

In the TCPC circulation, we have previously discovered that during exercise, the cardiac pump increases cardiac output, primarily by enhancing the heart rate and only come a lesser extent by raising stroke volume.2 This is in accordance v exercise research studies in healthy children.13

The respiratory pump had a pronounced result on IVC flow at rest, through an inspiratory flow fraction of 1.9. Wexler et al14 discovered that the velocity of IVC circulation in healthy adult men raised in inspiration and that this respiratory tract pump impact was more pronounced with supine lower-leg exercise. Rosenthal et al8 observed the TCPC-operated patients had a higher minute ventilation in ~ rest and a more far-ranging increase in respiratory tract rate beforehand in exercise 보다 controls, indicating the the work of breath may also be essential for pulmonary flow during exercise.

In our study, breathing became faster, the inspiratory step longer, and also the inspiratory IVC circulation rates greater during exercise. However, a similar increase in absolute expiratory flow rates resulted in lesser respiratory tract variations throughout exercise. Thus, the effect of the respiratory pump top top venous return v the IVC became relatively less essential with exercise.

The peripheral pump ide was occurred in the 1940s and also has been consistently demonstrated.15 The increase in flow and the reduction in retrograde circulation in the IVC throughout exercise might be explained by the greater blood flow from working muscles and also reduced venous capacitance in the reduced body half, attributable to stress and activity of the abdominal muscle and leg muscles.

In healthy and balanced subjects, upright bicycle exercise is connected with raising peripheral muscle contraction the produces an prompt increase in the gradient for venous return of greater than 4 mm Hg and an immediate central volume transition of approximately 1 together from the reduced limbs.16 In supine bicycle exercise, the peripheral pump has even much better working conditions, due to the fact that gravity is not an issue. After ~ a TCPC, the peripheral pump is probably the most essential factor for the copy of the IVC flow throughout exercise.


MR Method

This study offered separate quantitation that inspiratory and also expiratory flow. The real-time technique, although limited in spatial resolution, proved an extremely robust and permitted for measurements during physical exercise. No motion artefacts were present, since each image (flow-sensitive and also flow-insensitive) was got within 25 ms. The picture quality was identical for rest and also exercise flow measurements (Figure 1). The time resolution of around 20 frames per second was acceptable for looking at pulsatile flow phenomena. The comparison between the merged venous and aortic flow rates prove a typical difference between the independently derived flow measurements of much less than 6%.

The pure exercise flow values were similar to previous researches using MR flow measurements at hosted expiration2 and also mass spectrometry,8 indicating the accuracy of the technique.

Unlike volumetric flow rates acquired from Doppler recordings and single measurement of cross-sectional area,7 no presumption had to it is in made v respect to continuous cross-sectional area in the veins. This is important, because it has been demonstrated that the worse vena cava lateral tunnel collapses partially during a autumn in intrathoracic pressure.17

For the an initial time, we measured the actual circulation in IVC and SVC separately during both inspiration and expiration, and because major fluctuations were present, this turned the end to be important.

Unlike previous mr studies,5,18 our patients were no sedated.


Limitations

Supine lower-limb task is no the many common type of exercise. However, previous researches have displayed that both supine and upright bicycle exercise of similar workloads results in similar increments in heart price in TCPC-operated patients and also controls.8,19 Our choice of supine practice was dictated through the design and also capacity of the mr scanner. Mr scanners in i beg your pardon patients can sit up execute not however have enough resolution to perform this type of real-time circulation measurements.

Spatial resolution was limited because that the real-time flow an approach used and might have offered rise to partial volume-related circulation overestimation in the the smallest vessels. However, no systematic errors related to this phenomenon were present.

Because the the little field of view, no stationary tissue was existing to be used as recommendation for step correction. However, preliminary testing as well as the present results indicated that this was not a major problem. The use of a high-echo planar imaging element did no induce circulation void or various other detectable step errors, and echo time to be kept between 4 and also 5 ms.



Conclusion and Perspectives

In summary, the TCPC circulation functions with only 1 pumping chamber and also the 2 circulations in series. However, the absence of a subpulmonary ventricle go not average that flow to and through the lungs is a passive phenomenon. The current study suggests that the venous return in the TCPC circulation is affected by the cardiac output, respiration, and probably also a peripheral pump the acts with the muscles neighboring venous capacitance ship in the body and that the relative contribution the those 3 mechanisms transforms from remainder to exercise states.

Our findings are important not only since they check that detailed and also selective flow responses come exercise have the right to be investigated in children after facility cardiac surgery but also because they provide “normal values” for subjects with a great medium-term outcome after cavopulmonary surgery.

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The opportunity of obtaining detailed physiological circulation data throughout exercise in this group of patients with complex circulations offers clinicians with brand-new opportunities. It will be feasible to prospectively evaluate just how these flows adjust over time v alterations in ventricular function, arrhythmias, pregnancy, and the effects of practice training and drugs in the stability increasing team of patients who have actually undergone TCPC.