From the Department of Cardiothoracic and also Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experimental Clinical Research (T.F., E.M.P.), and Department of 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 Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experimental Clinical Research (T.F., E.M.P.), and Department of Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus College Hospital, Aarhus, Dennote.
E. Stenbøg

From the Department of Cardiothoracic and Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experimental Clinical Research (T.F., E.M.P.), and Department of Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus College Hospital, Aarhus, Dennote.
T. Fründ

From the Department of Cardiothoracic and also Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experimental Clinical Research (T.F., E.M.P.), and also Department of Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus University Hospital, Aarhus, Denmark.
M. Rahbek Schmidt

From the Department of Cardiothoracic and also Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experimental Clinical Research (T.F., E.M.P.), and also Department of Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus University Hospital, Aarhus, Dennote.
O. Kromann

From the Department of Cardiothoracic and also Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experipsychological Clinical Research (T.F., E.M.P.), and Department of Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus College Hospital, Aarhus, Dennote.
K. Sørensen

From the Department of Cardiothoracic and also Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experimental Clinical Research (T.F., E.M.P.), and Department of Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus College Hospital, Aarhus, Denmark.
E.M. Pedersen

From the Department of Cardiothoracic and Vascular Surgery (V.E.H., E.S., O.K.), MR Center, Institute of Experimental Clinical Research (T.F., E.M.P.), and Department of Cardiology (K.E., M.R.S., K.S., E.M.P.), Skejby Hospital, Aarhus College Hospital, Aarhus, Dennote.

Background— Little is known about blood flow and its relationship to respiration throughout exercise in patients through full cavopulmonary link (TCPC).

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Methods and Results— We stupassed away 11 patients 12.4±4.6 years (mean±SD) of age 5.9±2.8 years (mean±SD) after TCPC operation. Real-time MRI was supplied to meacertain blood flow in the premium vena cava (SVC), inferior vena cava (IVC), and also ascending aorta under inspiration and expiration in the time of supine lower-limb exercise (remainder, 0.5 and 1.0 W/kg) on an ergometer bicycle. IVC and also aortic flow increased from 1.60±0.52 and 2.99±0.83 L/min per m2 at rest to 2.58±0.71 and 3.97±1.20 L/min per m2 at 0.5 W/kg and also to 3.25±1.23 and also 4.62±1.49 L/min per m2 at 1.0 W/kg (P≤0.05). SVC circulation continued to be unadjusted. Resting circulation in the IVC was greater throughout motivation (2.99±1.25 L/min per m2) than in the time of expiration (0.83±0.44 L/min per m2) (inspiratory/suppose flow proportion, 1.9±0.5), and retrograde flow was existing throughout expiration (11±12% of intend flow). The predominance of inspiratory flow in IVC diminiburned with exercise to an inspiratory/mean circulation ratio of 1.5±0.2 (P≤0.05) and 1.4±0.3 at 0.5 and 1.0 W/kg, respectively.

Conclusions— In the TCCOMPUTER, circulation IVC and aortic yet not SVC flows boost with supine leg exercise. Inspiration facilitates IVC circulation at remainder yet less so throughout exercise, as soon as the peripheral pump seems to be more important.

Total cavopulmonary link (TCPC) is a palliative operation used in patients with complicated cardiac malformations that preclude a biventricular repair. The standard physiology of the TCPC circulation is a dissociation of the venous return from a ventricular power resource.

We formerly used MRI to examine flow in the time of breath organize in the TCPC circulation. At remainder, the pulmonary and also caval circulation was characterized by biphasic circulation and also pressure wavedevelops through maxima in atrial systole and also late ventricular systole.1 With supine bicycle exercise, blood circulation raised, generally attributable to an increase in heart rate and only slightly attributable to an increased stroke volume.2

Breapoint has a pronounced impact on circulation prices in the Fontan circulation at remainder,3–7 causing a principle of a respiratory pump that sucks blood right into the lungs during motivation.8 However, it is mostly unknown exactly how breathing affects flow during exercise.

The aim of the existing examination wregarding research the influence of breapoint on real-time antegrade and retrograde flow in the caval veins and also in the aorta throughout exercise in patients via TCPC.


Study Group

Elalso patients (age, 12.4±4.6 years ) were studied 5.9±2.8 years after TCCOMPUTER (Table 1). The operation had consisted of an end-to-side anastomosis between the exceptional vena cava (SVC) and also the right pulmonary artery and an extracardiac (n=1) or intraatrial (n=10) prosthetic baffle connecting the inferior vena cava (IVC) via the inferior surchallenge of the best pulmonary artery or the pulmonary primary trunk.
TABLE 1. Patient Characteristics

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

All patients were in New York Heart Association practical course I to II, in sinus rhythm, and without clinical indicators of congestive heart faitempt. Echocardiography perdeveloped within 3 months of the study showed excellent ventricular attribute and lack of aortic valve incompetence. Cardiac catheterization had actually been performed 3.2±1.9 years prior to the study and also disclosed unobstructed pathways.

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

Increated consent out under a protocol apshowed by the Danish Research Ethical Committee was obtained from all subjects or their parental fees.

Study Design

Patients were investigated throughout remainder and also exercise at 2 different workfill levels. They were inserted supine in the MRI scanner with 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 standard ECG-security system and also by pulse oxymeattempt (Nonin 8600 FO). Inspiration and also expiration were monitored with an air-filled belt placed on the abdomales and also connected by a 2-m-lengthy air tube to a push transducer.

Magnetic Resonance Imaging

MRI was perdeveloped using a Philips NT 1.5 Tesla whole-body scanner equipped via 21- and also 105-mT/m per ms gradients and also CPR6 study software program and also making use of an 18-cm receiver coil.

Standard scout imeras of the heart and good vessels were got in 3 orthogonal planes. From the scout images, double angulated circulation measurement planes were planned orthogonally to the SVC, IVC, and also ascfinishing aorta. In the SVC, circulation was measured automatically above the pulmonary anastomosis. Flow in the IVC was measured at the level of the lateral tunnel, above the coronary sinus. Aortic flow was measured in the ascending aorta.

Real-time flow dimensions were performed in random order in the IVC, SVC, and aorta at remainder and also in the time of exercise. Each measurement had 120 consecutive, real-time (no ECG triggering) phase-contrast flow acquisitions, each lasting 48 to 56 ms, giving a framework price of roughly 20 frames per second.

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

ECG and also respiratory wavecreates were synchronized via each circulation measurement and conserved for later on evaluation. Manual segmentation of vessels was performed utilizing dedicated software and volume flow for each of the 120 dimensions calculated (Figure).


Volume flow data from 1 patient synchronized to ECG and respiratory signal for both aorta, IVC and SVC at rest (left), and at 1 W/kg exercise (right). Values for all 120 real-time measurements are shown as a role of time for each series. With exercise, the ECG signal came to be progressively distorted.

For each circulation measurement, 2 to 4 respiratory cycles via 6.5 to 10 cardiac cycles were derived. The air-filled mechanism for respiratory measurement offered a hold-up of around 500 ms in between the respiratory movement of the patient and the appearance of the respiratory signal. All respiratory curves were corrected 500 ms backwards as necessary.

The beginning of the inspiratory phase was collection to the begin of the upward deflection and the start of expiration to the start of the downward deflection of the respiratory signal.

Exercise Protocol

Resting circulation dimensions were percreated through the feet in the pedals, positioned between 4 and also 22 cm above the scanner table. Hereafter, the patients perdeveloped continuous leg exercise at worklots of 0.5 and 1.0 W/kg. At each workfill, exercise was ongoing till the heart price was steady for 2 minutes. Flow measurements were then perdeveloped while the patient was still exercising. If exercise brought about misplacement of the measurement aircraft, a real-time scout lasting 15 secs was acquired, and the slice was repositioned and the flow measurement repeated.


Heart and also respiratory prices at each occupational level were calculated as the suppose worths over the moment throughout which flow measurements were performed in the 3 various measurement positions. Blood circulation and stroke volume were measured for 2 respiratory cycles. The begin and also the end of the 2 inspiratory and expiratory phases were identified from the respiratory waveforms. The size of the inspiratory phase relative to the entirety respiratory cycle (inspiratory fraction) was calculated. The intend circulation price from 2 inspiratory and from 2 expiratory phases, respectively, was computed, and also in its entirety expect circulation. Inspiratory circulation prices relative to suppose circulation rates during a full respiratory cycle (inspiratory circulation fraction) were calculated. When periods of retrograde blood flow were uncovered, the percent of the retrograde circulation loved one to the expect forward flow was calculated. Flow prices were indexed to body surconfront area and also expressed as liter per minute per square meter.

Statistical Analysis

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

The aortic and also caval circulation worths were compared in motivation and also expiration, and the retrograde flow percentage was compared in between exercise levels using 2-tailed paired t test. P≤0.05 was thought about significant.


All patients completed the protocol. The heart price and respiratory rate increased with raising levels of exercise (PTable 2). The inspiratory fractivity increased from the resting state to the exercise level of 0.5 W/kg (PTABLE 2. Heart Rate, Respiratory Rate, and Duration of Inspiratory Phase Relative to the Entire Respiratory Cycle (Inspiratory Fraction) During Flow Measurements at Rest and Throughout Exercise

Heart Rate, min−1Respiratory Rate, min−1Inspiratory FractionDocuments are mean±SD.*P≤0.05 compared via previous exercise 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 flow prices for the examine group and also the impact of respiration. Median aortic and IVC circulation rates boosted substantially via enhancing exercise, whereas SVC flow prices were unreadjusted. Aortic circulation rates were slightly lower (PTABLE 3. Average Blood Flow Rates (L/min per m2) in 2 Respiratory Cycles and the Corresponding Mean Flow Rates During Inspiration and Expiration in the Aorta, IVC, and SVC at Rest and at 2 Different Exercise Levels

AortaIVCSVCDocuments are mean±SD of measurements in the 11 patients. Inspiratory circulation prices family member to mean flow rates in a complete respiratory cycle (inspiratory flow fraction) are given for each vessel at each exercise level. NS suggests no considerable distinction compared through circulation rate at previous exercise level.*Monumental (P≤0.05) difference compared with flow rate at previous exercise level.†Significant (P≤0.05) distinction in between inspiratory and also expiratory circulation prices.Rest Flow in respiratory cycle2.99±0.831.60±0.521.26±0.34 Flow in inspiration2.85±0.732.99±1.251.26±0.32 Flow in expiration3.24±0.91†0.83±0.44†1.29±0.42 Inspiratory circulation 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) Flow 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 Flow in respiratory 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 at remainder and 47.4±13.2 and 48.2±15.6 mL/m2 at 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 boost in stroke volume through exercise was not statistically considerable.

Figure 2 reflects blood flow from 1 patient in relation to the respiratory and cardiac cycle at rest and also in the time of exercise at 1.0 W/kg. Aortic circulation rate at rest varied greatly in the cardiac cycle with a small retrograde circulation during diastole and showed almost no variation with respiration. Throughout exercise, flow rate increased slightly in the time of expiration. Resting IVC flow confirmed marked respiratory variation, via the greatest flow price developing throughout catalyst. Throughout exercise, the flow price enhanced and also the respiratory fluctuation was still current. SVC flow at rest and also in the time of exercise boosted slightly via motivation yet differed much less with respiration than IVC flow.

Correlation Between Aortic Flow Rates and also Systemic Venous Flow Rates

The intend aortic circulation rate differed less than 6% from the combined SVC and also IVC circulation prices. However before, as soon as looking separately at the inspiratory and expiratory phases, big variations in blood flow were discovered. At rest, the linked venous circulation rate was 51% greater than the aortic circulation throughout incentive (PPPPRetrograde Flow

Retrograde flow accounted for 2% to 3% of mean blood flow in the ascending aorta and also 0% to 1% in the SVC, with no transforms through exercise. Retrograde blood in IVC reduced from 10.5±12.4% of intend blood flow at rest to 2.9±4.0% in the time of exercise (PFlow Throughout Rest

The current study confirmed that relaxing IVC circulation has actually marked respiratory varicapacity in the TCCOMPUTER circulation.5,7 The impacts of breapoint were dual, through inspiratory facilitation and expiratory inhibition of the lower body venous rerevolve, in some patients leading to expiratory IVC flow reversal. Inspiratory augmentation of pulmonary blood flow after a timeless atriopulmonary anastomosis3,6 or a total cavopulmonary anastomosis4,9,10 has formerly been described.

The variations in intrathoracic pressure throughout breapoint are theoretically equally distributed to the IVC and SVC, however only IVC circulation was affected. This difference in caval circulation variation through respiration was more than likely attributable to a greater venous capacitance in the reduced body half, allowing for blood buildup in the veins of the lower body half during expiration and also mobilization of this pool throughout catalyst.

The present finding of an unified venous flow rate exceeding aortic flow price by 51% throughout motivation and being 34% lower during expiration shows that within the same respiratory cycle, the pulmonary circulation acts as a reservoir with a big inspiratory capacity. This may result in lessened left ventricular filling push in the time of incentive and therefore define why aortic circulation prices were lower throughout impetus. Tbelow is no previous description of this phenomenon in TCPC-operated patients, yet a 10% decrease in aortic flow in the time of inspiration has been discovered in healthy patients.11 Our finding of a tiny retrograde flow in the ascfinishing aorta is a normal phenomenon related to valve clocertain and also coronary perfusion.

Flow During Exercise

This is the first quantitative examine of MR-measured real-time volume circulation in TCPC-operated patients during exercise. Aortic and IVC flows raised through better levels of supine bicycling whereas SVC flows continued to be unadjusted, mirroring that the occupational lots were brought primarily by the muscles of the lower body fifty percent. The absolute flow worths and also the rise in flow are similar to what has been defined using respiratory mass spectrometry.8

To describe the facility hemodynamic alters throughout exercise, the principles of a cardiac pump, a respiratory pump, and also a peripheral pump have been introduced.12

In the TCCOMPUTER circulation, we have actually previously discovered that in the time of exercise, the cardiac pump boosts cardiac output, primarily by enhancing the heart price and also just to a lesser level by boosting stroke volume.2 This is in accordance through exercise researches in healthy and balanced youngsters.13

The respiratory pump had actually a pronounced result on IVC circulation at rest, via an inspiratory circulation fraction of 1.9. Wexler et al14 discovered that the velocity of IVC flow in healthy adult guys boosted in motivation and that this respiratory pump result was more pronounced through supine lower-leg exercise. Rosenthal et al8 observed that TCPC-operated patients had a higher minute ventilation at rest and a much more substantial increase in respiratory rate at an early stage in exercise than controls, indicating that the work of breapoint may likewise be essential for pulmonary flow during exercise.

In our examine, breapoint came to be much faster, the inspiratory phase much longer, and the inspiratory IVC flow rates greater in the time of exercise. However before, a similar boost in absolute expiratory flow rates led to lesser respiratory variations throughout exercise. Hence, the result of the respiratory pump on venous rerotate via the IVC ended up being fairly less crucial via exercise.

The peripheral pump principle was occurred in the 1940s and also has been repetitively demonstrated.15 The boost in circulation and the reduction in retrograde circulation in the IVC in the time of exercise may be explained by the higher blood circulation from functioning muscles and reduced venous capacitance in the reduced body fifty percent, attributable to anxiety and also task of the abdominal and also leg muscles.

In healthy and balanced subjects, upright bicycle exercise is linked via raising peripheral muscle contractivity that produces an instant rise in the gradient for venous rerotate of higher than 4 mm Hg and also an immediate main volume transition of approximately 1 L from the lower limbs.16 In supine bicycle exercise, the peripheral pump has even much better functioning problems, bereason gravity is not an concern. After a TCPC, the peripheral pump is probably the the majority of essential variable for the doubling of the IVC circulation in the time of exercise.

MR Method

This research gave separate quantitation of inspiratory and also expiratory flow. The real-time method, although restricted in spatial resolution, showed incredibly durable and permitted for measurements in the time of physical exercise. No movement artefacts were existing, bereason each picture (flow-sensitive and flow-insensitive) was obtained within 25 ms. The picture high quality was similar for rest and also exercise circulation dimensions (Figure 1). The time resolution of roughly 20 frames per second was acceptable for looking at pulsatile circulation phenomena. The comparison between the merged venous and also aortic circulation rates demonstrated a intend difference between the individually obtained circulation dimensions of less than 6%.

The absolute exercise flow worths were similar to previous studies utilizing MR circulation dimensions at held expiration2 and mass spectromeattempt,8 indicating the accuracy of the strategy.

Unchoose volumetric circulation rates gained from Doppler recordings and also single measurement of cross-sectional area,7 no presumption had to be made through respect to consistent cross-sectional area in the veins. This is necessary, because it has been demonstrated that the inferior vena cava lateral tunnel collapses partly in the time of a drop in intrathoracic push.17

For the first time, we measured the actual circulation in IVC and SVC independently during both catalyst and expiration, and bereason major fluctuations were existing, this turned out to be essential.

Unfavor previous MR studies,5,18 our patients were not sedated.


Supine lower-limb task is not the a lot of common type of exercise. However before, previous researches have presented that both supine and upideal bicycle exercise of comparable worktons outcomes in comparable increments in heart price in TCPC-operated patients and also controls.8,19 Our option of supine exercise was dictated by the design and capacity of the MR scanner. MR scanners in which patients can sit up do not yet have actually sufficient resolution to perdevelop this kind of real-time flow dimensions.

Spatial resolution was limited bereason of the real-time flow technique offered and also might have actually offered increase to partial volume-connected flow overestimation in the smallest vessels. However, no methodical errors regarded this phenomenon were current.

Since of the tiny field of see, no stationary tconcern was current to be offered as reference for phase correction. However before, preliminary trial and error and also the existing results suggested that this was not a major problem. The use of a high-echo planar imaging aspect did not induce circulation void or other detectable phase errors, and echo time was retained in between 4 and 5 ms.

Conclusion and also Perspectives

In summary, the TCPC circulation works through only 1 pumping chamber and the 2 circulations in series. However before, the absence of a subpulmonary ventricle does not suppose that flow to and through the lungs is a passive phenomenon. The current examine indicates that the venous rerotate in the TCPC circulation is affected by the cardiac output, respiration, and most likely additionally a peripheral pump that acts with the muscles bordering venous capacitance vessels in the body and that the family member contribution of those 3 mechanisms changes from remainder to exercise claims.

Our findings are crucial not only because they confirm that detailed and also selective flow responses to exercise can be investigated in children after complex cardiac surgical treatment yet also because they carry out “normal values” for subjects with an excellent medium-term outcome after cavopulmonary surgical treatment.

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The possibility of obtaining in-depth physiological circulation information throughout exercise in this team of patients through complex circulations provides clinicians via new avenues. It will be feasible to prospectively evaluate just how these flows readjust over time with alterations in ventricular function, arrhythmias, pregnancy, and also the impacts of exercise training and also drugs in the steadily boosting team of patients that have undergone TCCOMPUTER.