Am J Physiol Heart Circ Physiol 295: H197-H201, 2008.
First published April 25, 2008; doi:10.1152/ajpheart.00876.2007
0363-6135/08 $8.00
Structure and torsion of the normal and situs inversus totalis cardiac left ventricle. I. Experimental data in humans
Tammo Delhaas,1,2
Wilco Kroon,2
Wim Decaluwe,1
Mirjam Rubbens,4
Peter Bovendeerd,4 and
Theo Arts3
1Department of Pediatrics, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, and Departments of 2Physiology and 3Biophysics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht; and 4Department of Biomedical Technology, Eindhoven University of Technology, Eindhoven, The Netherlands
Submitted 26 July 2007
; accepted in final form 14 April 2008
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ABSTRACT
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In 1926, the famous American pediatric cardiologist, Dr. Helen B. Taussig, observed that in situs inversus totalis (SIT) main gross anatomical structures and the deep muscle bundles of the ventricles were a mirror image of the normal structure, while the direction of the superficial muscle bundles remained unchanged (H. B. Taussig, Bull Johns Hopkins Hosp 39: 199–202, 1926). She and we wondered about the implication of this observation for left ventricular (LV) deformation in SIT. We used magnetic resonance tagging to obtain information on LV deformation, rotation, and torsion from a series of tagged images in five evenly distributed, parallel, short-axis sections of the heart of nine controls and eight persons with SIT without other structural (cardiac) defect. In the controls, during ejection, the apex rotated counterclockwise with respect to the base, when looking from the apex. Furthermore, the base-to-apex gradient in rotation (torsion) was negative and similar at all longitudinal levels of the LV. In SIT hearts, torsion was positive near the base, indicating mirrored myofiber orientations compared with the normal LV. Contrary to expectations, torsion in the apical regions of SIT LVs was as in normal ones, reflecting a normal internal myocardial architecture. The transition zone with zero torsion, found between the apex and base, suggests that the heart structure in SIT is essentially different from that in the normal heart. This provides a unique possibility to study regulatory mechanisms for myocardial fiber orientation and mechanical load, which has been dealt with in the companion paper by Kroon et al.
cardiac development; adaptation; magnetic resonance imaging; mechanics; myocardium; ventricular function
IN 1926, THE FAMOUS AMERICAN pediatric cardiologist, Dr. Helen B. Taussig, described in two cases of situs inversus totalis (SIT) that main gross anatomical structures and the deep muscle bundles of the ventricles were a mirror image of the normal heart, while the direction of the superficial muscle bundles remained unchanged (10). She also speculated as to the physiological significance of the muscle layer arrangement: "In view of the fact that the position of the deep muscle layers of the heart gives the mirror image of the normal constituting the preponderant contractile mass, the superficial layer being relatively thin by comparison, one would expect the systolic rotation about the anatomical axis of the transposed heart to be the mirror image of the normal" (10). The intriguing finding of Dr. Taussig remained unnoticed in cardiology, except for a limited number of studies from Japan in 1987 (2) and 1990 (8) that confirmed her original observation that the superficial layer of morphological left (LV) and right ventricles in SIT does not display the mirror image of that in situs solitus (SS = normal organ arrangement). Her speculation on rotation was never tested experimentally. In fact, the assumption that the inner layers dominate the outer ones is debatable, since the large radius of the latter layers adds to a high mass and moment arm. In 1926, observations on cardiac rotation could only be made during cardiac surgery. Nowadays, we can noninvasively estimate cardiac rotation and torsion by means of magnetic resonance (MR) tagging. Given the possibilities of the latter technique, we assessed whether the myofiber pattern within the LV wall in SIT leads to the same, although inverse, LV deformation pattern as in normal subjects.
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METHODS
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Experimental subjects.
Nine healthy controls [1 female, 8 males; age 10–56 yr (median 30 yr)] and eight persons with SIT [3 females, 5 males; age 8–70 yr (median 23 yr)] were investigated. Six of the latter group had Kartagener syndrome, generally characterized by SIT, ciliary dyskinesia, variable impairment of fertility, and sinusitis with or without bronchiectasis with chronic cough. In our study, none of the SIT group had bronchiectasis or other structural (cardiac) defects or abnormalities. Subjects were included only if no evidence of preexisting cardiac disease or other significant coexisting illness was found in a clinical examination. Exclusion criteria included a history of hypertension, diabetes, ischemic or valvular heart disease, regular use of medication for cardiovascular illness, or a resting blood pressure above 160/90 mmHg. On the 12-lead ECG, atrial fibrillation, bundle branch block, pathological Q waves, LV hypertrophy, or changes consistent with myocardial ischemia resulted also in exclusion. The investigation conformed to the principles outlined in the Declaration of Helsinki. The Medical Ethics Committee of the University Hospital Maastricht approved the research protocol, and informed consent was obtained from all participants.
Image acquisition and analysis.
MRI experiments were performed at 1.5 T (Gyroscan NT, Philips Medical Systems, Best, The Netherlands). Images were acquired in breath hold using ECG triggering, starting 20 ms after the R-wave. Using spatial modulation of the magnetization (3), two series of line-tagged images with lines in either horizontal (septal-lateral) or vertical (antero-posterior) direction were obtained over a period of 80–90% of the cardiac cycle in five evenly distributed, parallel, short-axis (SA) sections of the heart. Additionally, balanced fast-field echo (nontagged) reference cine images were made. The following parameter settings were used: phase interval, 
20 ms; slice thickness, 8 mm; intertag distance, 5 mm; field of view, 200 mm for children and 250 mm for adults; image size, 256 x 256 pixels.
MR images were analyzed offline with custom software using Matlab 7.0 (MathWorks, Natick, MA) (11). The LV wall was manually outlined for each slice in a midsystolic cine image. This frame functions as reference for the displacement measurements to minimize errors due to large deformation. The tagged images were spatially band filtered around the line tag frequency (spatial frequency 0.14 mm–1, ratio of bandwidth to center frequency 1.0). The negative counterpart of the frequencies was filtered out. Applying two-dimensional inverse Fourier transformation to both filtered spectra, band filtered images resulted with a complex amplitude per pixel. Next, local phase and local frequency were derived. With the use of a correlation method previously applied for pulsed ultrasonic echo signals (4), vertical displacement maps for each time interval were calculated from the successive images with horizontal tag lines, whereas horizontal displacement maps were obtained from the images with vertical tag lines. Displacement per pixel was determined as the phase difference between both images, divided by the local spatial frequency, which has been determined as the local phase shift per pixel. Thus horizontal and vertical displacement maps were derived from pairs of vertically and horizontally tagged images, respectively.
Using the derived two-dimensional displacement information for each slice, rotation (
) of the LV wall was calculated as the average of rotational movement of each pixel within the wall about the centroid of the cavity. Cavity area (Ac,t) was estimated as the sum of the manually outlined cavity area in the reference image and the change of this area relative to that in the outlined image. The end of the ejection phase was defined as the moment in time where –dAc,t/dt, averaged over all slices, approximated zero. Wall area (Aw) was calculated in the reference frame as the area between the epi- and endocardial contours. For each section between subsequent slices, torsion (T) was calculated as the longitudinal gradient in rotation angle multiplied by the average of the outer radii (ro) of the upper (l) and lower (u) slice of that section:
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with d denoting the distance between the two SA cross sections. Physically, this measure of torsion may be interpreted as the longitudinal-circumferential shear angle on the epicardial surface between the SA cross sections.
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RESULTS
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The balanced fast-field echo nontagged cine images revealed normal cardiac anatomy and organ position in the control group, whereas these gross anatomy entities were mirror imaged in SIT.
For a 35-yr-old man with SS (=normal situation), rotation of five LV SA slices and torsion of the enclosed four sections are shown as a function of time in Fig. 1, A and B. During practically the whole cardiac cycle, when viewing from the apex, the rotation angle remained positive for all five LV SA slices, indicating counterclockwise rotation with respect to the end-diastolic reference frame. Rotation rate is the first derivative of the rotation angle over time, i.e., the slope of the lines in Fig. 1A. The sign of this rotation rate indicates the instantaneous direction of the rotation movement. Thus rotation of all slices was counterclockwise in early systole, reflecting a counterclockwise rotation of the whole heart. Thereafter, for the different slices, rotation diverges. The apical slice continues to rotate counterclockwise toward the end of the ejection phase, whereas the most basal slice rotates back in a clockwise direction. The slices in between apex and base show gradual transition patterns. At the end of the ejection phase, the rotation angle increases gradually from base to apex. As a result, torsion, being proportional with the longitudinal gradient in rotation angle, is about uniform for all four sections during systole. The negative sign of torsion indicates that, looking from the apex, the LV apex rotates more counterclockwise than the LV base.
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Fig. 1. Time course of rotation angle and torsion of left ventricular (LV) short-axis slices in a normal subject and in one with situs inversus totalis (SIT). Positive rotation is counterclockwise when viewing the heart from the apex. Zero time corresponds to 20 ms after the R-wave. A and B: in the normal subject, the rotation angle at the end of the ejection phase increases gradually from base to apex. As a result, torsion, being proportional to the longitudinal gradient in rotation angle, is about uniform during systole for all 4 enclosed sections. C and D: in the SIT, LV early systolic rotation is opposite to normal. Thereafter, all slices rotate counterclockwise, albeit with different pace. At the end of the ejection phase, the apex rotated most counterclockwise just as the base did, although to a lesser degree. Net rotation of the midventricular slice is practically zero. Near the apex, torsion is about normal, whereas, near the base, torsion is inverted. As a transition, torsion for the zone between slices 3 and 4 is about zero. ccw, Counterclockwise; cw, clockwise; ee, end of the ejection phase.
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LV rotation and torsion patterns for a 30-yr-old man with SIT are shown in Fig. 1, C and D. Early in systole, the SIT heart rotates inversely compared with the normal situation. All slices rotate clockwise, although the slices halfway between apex and base rotate most. Both apex and base rotate less and to about the same amount with respect to the reference frame. From midsystole, rotation becomes counterclockwise, but for all slices with a different pace. At the end of the ejection phase, the apex has the largest counterclockwise rotation angle with respect to the reference frame, followed by the slice near the base. At the end of the ejection phase, there is no net rotation of the midventricular slice, whereas the slices in between midventricle and apex are about equally rotated clockwise. Using the fact that torsion is proportional to the base-to-apex gradient of rotation, apical and basal torsion appear opposite. Near the base, torsion is inverted (u > l), whereas, near the apex, torsion is about normal (u < l). As a transition, torsion for the zone between slices 3 and 4 is about zero (u = l).
Figure 2 summarizes the results on torsion from the beginning to end of ejection, here called systolic torsion, of the subjects studied. The asterisks indicate the subjects presented in more detail in Fig. 1. In the middle panel, LV systolic torsion is indicated for the four sections studied in normal subjects and in SIT. It clearly shows that in normal subjects the amount of LV systolic torsion is in a rather narrow range for all four sections in all subjects studied. Apart from rigid body motion, LV rotation is counterclockwise relative to the basal slice, as viewed from the apex. Systolic torsion, quantified as the longitudinal gradient in LV systolic rotation angle, multiplied by outer radius, is about uniform from apex to base in normal subjects, being –0.13 ± 0.03, –0.12 ± 0.02, –0.13 ± 0.02, and –0.13 ± 0.03 rad.
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Fig. 2. Systolic torsion of the LV in normal subjects and in those with SIT. Asterisks indicate the subjects presented in more detail in Fig. 1. In normal subjects (red lines), systolic LV torsion around the long axis is about uniform for all 4 sections in all subjects studied. In SIT (black lines), systolic LV torsion is nonuniform with relatively large interindividual and intraventricular differences. The solid yellow line connects the mean values for each section. Near the apex, torsion is as in normal subjects. In the more basal sections, torsion gradually changes to an inverted torsion near the base. Frontal views are shown of the ventricular chambers in normal subjects (left) and SIT (right). The solid epicardial reference lines for beginning of ejection deform to the dashed lines at the end of ejection. The normal LV, as viewed from the apex, exhibits a counterclockwise apical rotation with respect to the base. Apart from rigid body motion, LV motion in SIT can be described as having fixed both base and apex, while the midventricle rotates clockwise in between, as viewed from the apex.
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In contrast, LV systolic torsion in SIT is nonuniform. Interindividual differences are rather large, and large differences are found between base and apex. Despite the interindividual differences, a common pattern can be observed, as depicted by the solid yellow line connecting the mean values of systolic torsion for each section. In the apical section, systolic torsion is in a normal direction, with amplitude somewhat lower than normal (–0.08 ± 0.05 rad). The following, more midventricular section exhibited hardly any systolic torsion (–0.01 ± 0.07 rad), whereas both the midventricular and basal sections have slight positive systolic torsion, being 0.02 ± 0.08 and 0.03 ± 0.06 rad, respectively. Therefore, apart from rigid body motion, LV systolic motion in SIT can be described as having fixed both base and apex, while the midventricle rotates clockwise in between, as viewed from the apex.
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DISCUSSION
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Our results clearly show that, although gross anatomy is mirror imaged in SIT, this is not the case for LV systolic deformation. Whereas LV torsion in normal subjects is negative and about uniform for all four sections studied, in SIT apical and basal torsion were opposite. Near the base, torsion is indeed inverted compared with normal subjects, but, near the apex, torsion has the same direction and almost the same amplitude as in normal subjects.
Torsion is closely related to the distribution of myofiber orientation. In the normal SS heart, subepicardial fibers follow the path of a left-handed helix around the cavity, fibers in the midwall are circumferentially oriented, and subendocardial fibers follow a right-handed helical path (5, 9). Due to this specific pattern of fiber orientation, shortening of subendocardial fibers during systole tends to rotate the apex in a clockwise direction with respect to the base, while shortening of the subepicardial fibers tends to rotate the apex in the opposite direction. Since we measured a counterclockwise apical rotation with respect to the base, we conclude that the subepicardial fibers dominate the subendocardial ones in SS, as far as torsion is concerned. The negative torsion of the apical half of the LV in SIT is about normal, suggesting that the myocardial fiber orientation pattern is as in normal subjects. The positive torsion of the LV basal half in SIT suggests an inverted fiber orientation pattern in the basal region. In the midventricular sections with hardly any torsion, the pattern of fiber orientation is thought to be a mixture of an inverted (basal type) inner half fiber pattern and a normal (apical type) outer half fiber pattern. The latter suggestion on the pattern of fiber orientation in SIT is supported by anatomical studies on LV myocardial fiber orientation in humans (2, 6, 8, 10). In Fig. 3, we depict myocardial fiber angles in the LV anterior wall as derived from data in these studies.1 From these data, it can be appreciated that in normal hearts the pattern of the transmural change in fiber angle is qualitatively the same for the apex and the base of the LV. The SIT hearts, however, show a completely different pattern for the base and the apex. Whereas the apex of all SIT hearts studied shows the same pattern of transmural change in fiber angle as in the normal heart, the base of the SIT hearts has a partly mirror-imaged pattern of the transmural change in fiber angle. This difference is best appreciated in the SIT heart evaluated by Asami and Koizumi (2). The myocardial fiber angle at the epicardium and the subepicardium of the anterior wall of the base of the SIT LV is as in the normal heart, whereas the deeper layers show an inverted pattern. It is to be noted that, although data regarding other areas than the anterior wall are not complete in the studies referenced in Fig. 3, regional variation in the transmural course exists (2, 6, 8). Asami's abstract states: "The exception to this tendency (namely an inverted myofiber orientation pattern in the deeper layers of the basal levels) was found at the posterior region of the morphologically LV, in which there was no mirror imaging but a normal pattern throughout the depth of the wall." This regional variation in fiber orientation pattern may also account for the differences in torsion pattern found within the SIT group (see below).
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Fig. 3. Transmural course of the fiber angle in the LV anterior wall in normal human hearts [situs solitus (SS); top] and in human SIT hearts (bottom). Data are derived from Refs. 2, 6, and 8.
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Ventricular torsion has been identified as a mechanism to reduce differences in fiber shortening within the LV wall. In the absence of torsion, during ejection, the amount of circumferential shortening, and hence fiber shortening, would be larger in subendocardial layers than in subepicardial layers. Torsion reduces subendocardial fiber shortening and amplifies subepicardial fiber shortening, leading to a more homogeneous distribution within the LV wall of fiber shortening during ejection (1). Mathematical model studies indicated that the specific helical myofiber pattern is needed to accommodate homogeneous fiber shortening. The specific fiber structure has been suggested to be the result of a myocardial adaptation process (1). In SIT, the LV rotation and torsion, as well as the helical myofiber pattern within the LV wall, are not a mirror image of the normal pattern: two poles of different functional (our study) and anatomical (2, 8, 10) symmetry were found. Therefore, the SIT heart provides a unique possibility to study regulatory mechanisms for myocardial fiber orientation and mechanical load. This has been explored in detail in the accompanying computational study by Kroon et al. (7).
Differences in the pattern of torsion between normal subjects and those with SIT cannot be explained by differences in heart rate variability or right ventricular and/or LV loading conditions between the two groups. None of our subjects had conduction disturbances, myocardial infarct, or signs of (pulmonary) hypertension. In the normal heart, through-slice motion will not affect observed torsion, because the longitudinal gradient in rotation angle is about uniform. In SIT, some differences in torsion may be attributed to through-slice motion, but it cannot explain the found dramatic difference between apical and basal torsion pattern. The variation in measured patterns of torsion in SIT suggests that every single SIT patient has a unique fiber orientation pattern, especially in the more basal parts of the LV. Deformation in these more basal parts of the LV influences, of course, the torsion pattern in the apical part. Also, regional variations in fiber orientation pattern, as well as transmural depth at which the normal fiber orientation pattern changes to an inverted one, influence the sign and amplitude of systolic torsion. Future, more detailed studies on the anatomy and deformation of both apical and basal slices might shed more light on the differences found for the torsion pattern within the SIT group.
Early systolic inverted rotation of the whole SIT heart is more likely to be due to the attachment of the heart by the large blood vessels than due to inversion of the internal myofiber structure near the base. After all, just after pulmonary valve opening, pressure in the pulmonary artery rises quickly, causing the RV outflow tract to increase in length and diameter. Consequently, the RV is pushed backward, causing whole heart rotation of the normal heart, as well as inverted rotation of the SIT heart.
In conclusion, although gross anatomy is mirror imaged in SIT, the LV systolic deformation pattern is only partially mirror imaged. In the normal heart, LV torsion is negative and quite uniform from base to apex. In SIT hearts, torsion is positive near the base, but negative near the apex. The sign of torsion reflects the handedness of the helical fiber pathways in the wall. In the SIT heart, mirrored torsion near the base reflects mirrored fiber structure. Contrary to expectations, near the apex torsion was as in normal subjects, reflecting a normal internal myocardial architecture. The transition zone with zero torsion between both types in myocardial architecture makes the SIT heart structure essentially different from the normal heart. Therefore, the SIT heart provides a unique possibility to study regulatory mechanisms for myocardial fiber orientation and mechanical load [see companion paper by Kroon et al. (7)].
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GRANTS
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This study was supported by Grant 2000T036 from the Netherlands Heart Foundation and Grant PF155 from the University Hospital Maastricht. T. Delhaas is a Clinical Fellow of the Netherlands Heart Foundation (Dr. E. Dekker Fund).
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ACKNOWLEDGMENTS
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We thank Anneke van Susteren (Dept. of Biophysics) and Dr. Gabriël Snoep (Dept. of Radiology) for help in the data collection.
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FOOTNOTES
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Address for reprint requests and other correspondence: T. Delhaas, Depts. of Physiology and Pediatrics, Cardiovascular Research Institute Maastricht, Maastricht Univ. and Univ. Hospital Maastricht, P. O. Box 5800, NL-6202 AZ Maastricht, The Netherlands (e-mail: t.delhaas{at}fys.unimaas.nl)
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Data from Matsamura et al. (8) are derived from their Figure 1 (epicardial fiber angles in situs solitus), Figures 4 and 5 (epicardial fiber angles in situs inversus totalis), and Table 2 (fiber angles for the deeper layers in situs solitus and situs inversus totalis). Data from Asami and Koizumi (2) are derived from their Figure 4. Data from Greenbaum (6) are derived from their Figure 16, Blocks 1–3. 
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REFERENCES
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- Arts T, Bovendeerd PHM, Prinzen FW, Reneman RS. Relation between left ventricular cavity pressure and volume and systolic fiber stress and strain in the wall. Biophys J 59: 93–102, 1991.[Web of Science][Medline]
- Asami I, Koizumi K. [The vortex cordis is never reversely directed, even in situs inversus and L-loop anomaly]. Kaibogaku Zasshi 64: 36–45, 1989.[Medline]
- Axel L, Dougherty L. MR imaging of motion with spatial modulation of magnetization. Radiology 171: 841–845, 1989.[Abstract/Free Full Text]
- de Jong PGM, Arts T, Hoeks APG, Reneman RS. Determination of tissue motion velocity by correlation interpolation of pulsed ultrasonic echo signals. Ultrason Imaging 12: 84–98, 1990.[CrossRef][Web of Science][Medline]
- Geerts L, Bovendeerd P, Nicolay K, Arts T. Characterization of the normal cardiac myofiber field in goat measured with MR-diffusion tensor imaging. Am J Physiol Heart Circ Physiol 283: H139–H145, 2002.[Abstract/Free Full Text]
- Greenbaum RA, Ho SY, Gibson DG, Becker AE, Anderson RH. Left ventricular fibre architecture in man. Br Heart J 45: 248–263, 1981.[Abstract/Free Full Text]
- Kroon W, Delhaas T, Bovendeerd P, Arts T. Structure and torsion in the normal and situs inversus totalis cardiac left ventricle. II. Modeling cardiac adaptation to mechanical load. Am J Physiol Heart Circ Physiol. First published April 18, 2008; doi:10.1152/ajpheart.00877.2007.[Abstract/Free Full Text]
- Matsumura H, Aizawa Y, Kumaki K. Myocardial architecture in situs inversus viscerum totalis. In: Developmental Cardiology: Morphogenesis and Function, edited by Clark EB and Takao A. Mount Kisco, NY: Futura, 1990, p. 605–624.
- Streeter DD, Hanna WT. Engineering mechanics for successive states in canine left ventricular myocardium. II. Fiber angle and sarcomere length. Circ Res 33: 656–664, 1973.[Abstract/Free Full Text]
- Taussig HB. The anatomy of the heart in two cases of situs transversus. Bull Johns Hopkins Hosp 39: 199–202, 1926.[Web of Science]
- van der Toorn A, Barenbrug P, Snoep G, van der Veen FH, Delhaas T, Prinzen FW, Maessen J, Arts T. Transmural gradients of cardiac myofiber shortening in aortic valve stenosis patients using MRI tagging. Am J Physiol Heart Circ Physiol 283: H1609–H1615, 2002.[Abstract/Free Full Text]
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W. Kroon, T. Delhaas, P. Bovendeerd, and T. Arts
Structure and torsion in the normal and situs inversus totalis cardiac left ventricle. II. Modeling cardiac adaptation to mechanical load
Am J Physiol Heart Circ Physiol,
July 1, 2008;
295(1):
H202 - H210.
[Abstract]
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Copyright © 2008 by the American Physiological Society.
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