Computational model of aortic valve surgical repair using grafted pericardium

Aortic valve reconstruction using leaflet grafts made from autologous pericardium is an effective surgical treatment for some forms of aortic regurgitation. Despite favorable outcomes in the hands of skilled surgeons, the procedure is underutilized because of the difficulty of sizing grafts to effectively seal with the native leaflets. Difficulty is largely due to the complex geometry and function of the valve and the lower distensibility of the graft material relative to native leaflet tissue. We used a structural finite element model to explore how a pericardial leaflet graft of various sizes interacts with two native leaflets when the valve is closed and loaded. Native leaflets and pericardium are described by anisotropic, hyperelastic constitutive laws, and we model all three leaflets explicitly and resolve leaflet contact in order to simulate repair strategies that are asymmetrical with respect to valve geometry and leaflet properties. We ran simulations with pericardial leaflet grafts of various widths (increase of 0%, 7%, 14%, 21% and 27%) and heights (increase of 0%, 13%, 27% and 40%) relative to the native leaflets. Effectiveness of valve closure was quantified based on the overlap between coapting leaflets. Results showed that graft width and height must both be increased to achieve proper valve closure, and that a graft 21% wider and 27% higher than the native leaflet creates a seal similar to a valve with three normal leaflets. Experimental validation in excised porcine aortas (n=9) corroborates the results of simulations.     

Pulmonary Artery Reconstruction Using Autologous Pericardium or Azygos Venae Substitute for Surgical Treatment of Central Non-Small Cell Lung Cancer

We evaluated the clinico-surgical significance of pulmonary artery (PA) reconstruction using a patch of autologous pericardium/azygos venae substitute to treat central non-small cell lung cancer in 62 patients with pulmonary arteries invaded by tumor. According to TNM-classification, four patients were stage IIb, 46 were stage IIIa, and 12 were stage IIIb. Depending on tumor infiltration, surgical procedures included partial PA tangential resections/reconstructions by a patch of autologous azygos venae, a patch of autologous pericardium and complete PA sleeve resection and reconstruction by a custom-made autologous pericardial conduit interposition. 47 patients received postoperative chemotherapy and 19 received radiotherapy. There were 2 (3.2 %) postoperative early deaths due to bronchial anastomotic leakage. Postoperative complications occurred in 17.7 % (11/62) patients and all recovered uneventfully. Mean follow-up time after surgical resection was 49.5 (6–12) months and overall ≤1-, 3-, 5-, and ≥10-year survival rates were 80.2, 44.7, 31.4, and 23.1 %, respectively. It was concluded that autologous pericardial patch and azygos vein patch reconstruction of PA were safe and effective. Regarding extended circumferential defects after sleeve resection in which end-to-end anastomosis is not feasible, autologous pericardial conduit interposition may be useful for reconstruction when a tumor extensively infiltrates full circumference of the PA.     

去细胞牛颈静脉构建组织工程右心带瓣管道体内实验初步研究

目的：将体外构建的组织工程右心带瓣管道,以带瓣补片的形式移植于犬主肺动脉,观测带瓣管道材料体内情况。方法：去细胞处理牛颈静脉体,无菌处理后种植标记过的犬骨髓间质干细胞,构建组织工程带瓣管道,犬开胸手术,将体外构建的组织工程右心带瓣管道,以带瓣补片的形式移植于犬主肺动脉,术后4、8、12行胸部B超检查;取出补片,HE染色;荧光显微镜下标记细胞检测;样本钙含量测定。结果：术后犬胸部B超观察：瓣叶无增厚,钙化,管道血流通畅,无血栓及钙化。术后4、8、12周除了瓣叶逐渐缩小外,补片无动脉瘤形成,瓣膜表面光滑,无血栓形成,弹性良好,血管壁内面光滑,无血栓形成。种植种子细胞牛颈静脉带瓣补片成活。4周钙含量增加,8周时候,钙含量又有增加,12周时钙含量与8周相比无明显变化。结论：组织工程技术构建组织工程右心带瓣管道有可行之处。     

Functional analysis of bioprosthetic heart valves

Glutaraldehyde-treated bovine pericardium is used successfully as bioprosthetic material in the manufacturing of heart valves leaflets. The mechanical properties of bovine pericardial aortic valve leaflets seem to influence its mechanical behaviour and the failure mechanisms. In this study the effect of orthotropy on tricuspid bioprosthetic aortic valve was analysed, using a three-dimensional finite element model, during the entire cardiac cycle. Multiaxial tensile tests were also performed to determine the anisotropy of pericardium. Seven different models of the same valve were analysed using different values of mechanical characteristics from one leaflet to another, considering pericardium as an orthotropic material. The results showed that even a small difference between values along the two axes of orthotropy can negatively influence leaflets performance as regard both displacement and stress distribution. Leaflets of bovine pericardium bioprostheses could be manufactured to be similar to natural human heart valves reproducing their well-known anisotropy. In this way it could be possible to improve the manufacturing process, durability and function of pericardial bioprosthetic valves.     

Creep of the canine pericardium in vivo

In eight open chest dogs we assessed the creep of the pericardium by measuring the increase in surface area of the pericardium, occurring after pericardial surface pressure (Ppe) was rapidly increased by inflating an air-containing balloon positioned between the pericardium and the left ventricular (LV) epicardium. We observed an increase in LV end diastolic pressure (EDP) of 3.6 +/- 3.4 mmHg (1 mmHg = 133.3 Pa) (p less than 0.05) (mean +/- SD) and a reduction in LV anteroposterior (AP) diameter of 8.8 +/- 6.1 mm (p less than 0.01), both of which were stable after 10 s. Mean Ppe increased 11.6 +/- 3.3 mmHg (p less than 0.001). Pericardial surface lengths at 45 and 135 degrees to the long axis of the LV were measured with two pairs of ultrasonic crystals attached to the outer surface of the pericardium. The beam of ultrasound travelling between each pair was directed parallel to the pericardial surface through a film of conducting medium. Initial increase in surface area (calculated as the product of two pericardial lengths) occurring during the first 15 s after balloon inflation was 5.8 +/- 2.5% (p less than 0.001). During the next 30 min, while mean pericardial pressure did not change, pericardial surface area increased another 2.8% (p less than 0.005). This time-dependent 2.8% increase in pericardial surface area (equivalent to an increase in volume of approximately 5%) is due to creep.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pericardium and cardiac transmural filling pressure in the fetal sheep

Fetal pericardial physiology may be important for understanding normal and abnormal circulatory states. Right atrial, pericardial, thoracic, and amniotic fluid pressures were measured simultaneously in chronically-instrumented, near-term fetal sheep. Fourteen experiments were performed in 8 fetuses 4-21 days after surgery. The pressure gradient from the right atrium to the amniotic fluid and its components (transatrial, transpericardial and transthoracic pressures) were measured during control and with rapid infusion and withdrawal of blood. Under control conditions, right atrial minus amniotic pressure was 3.2 +/- 1.8 (SD) torr, right atrial minus pericardial pressure 2.5 +/- 1.7, pericardial minus thoracic pressure 0.6 +/- 0.7, and thoracic minus amniotic pressure 0.1 +/- 1.4. At right atrial pressures above control, pericardial minus thoracic pressure rose linearly with right atrial minus thoracic pressure. The average regression coefficient was 0.50 with an intercept of -1.5 torr. Administration of dextran-saline solution (121% of estimated blood volume) over 2-4 hs in 10 experiments did not reduce the pericardial minus thoracic to right atrial minus thoracic pressure relationship. Fluid added to the pericardium of three lambs progressively shifted the pericardial minus thoracic to right atrial minus thoracic pressure relationship up and to the left. The pericardial minus thoracic to right atrial minus thoracic pressure relationship was unaffected by fetal growth. Thus, the fetal pericardium affects cardiac filling pressures. The affect of the pericardium is increased markedly by pericardial liquid but is unchanged during growth.     

Pericardial heterograft valves: An assessment of leaflet stresses and their implications for heart valve design

Bovine pericardium, stabilized with glutaraldehyde, is used widely in the construction of heart valve substitutes, but the design and construction of valve substitutes from this material are empirically based. Collagenous tissue can support tension, but experimental evidence indicates that flexure-induced compressive stresses can lead to fatigue failure. This study uses experimental results obtained from cyclic uniaxial load tests to predict the type and magnitude of operational stresses which occur in pericardial heterograft leaflets. Both Young's modulus and Poisson's ratio varied with uniaxial loading in pericardium, chemically modified free of tension. Leaflet stresses were analysed by using effective incremental representations of these parameters. In leaflets with unrestricted rotation at the point of attachment to the stent, the mid-plane tensions always exceeded the bending stresses, and no zones of leaflet compression were predicted. In contrast, with totally restricted leaflet rotation induced by clamping (possibly between a male and female frame) the bending stresses were greater than the mid-plane tensions at the hinge line and significant compressive stresses were predicted at this site. If elastic boundary conditions were introduced at the stent (possibly by wrapping the stent in pericardium) then the compressive stresses were reduced as the degree of elasticity was increased. Glutaraldehyde fixation of the pericardium under load produced a stiffer material; higher compressive stresses at the stent and significant increases in total stress were predicted for this tissue. The application of elevated pressure loading also increased the compressive and total stresses in the leaflet. Finally, it was shown that bicuspid leaflets were likely to experience higher stresses than tricuspid leaflets. This simple stress analysis should help valve designers of pericardial heterografts to identify those conditions which lead to tissue compression, high total stress, and ultimately material fatigue.     

MRI-determined left ventricular "crescent effect": a consequence of the slight deviation of contents of the pericardial sack from the constant-volume state

During one cardiac cycle, the volume encompassed by the pericardial sack in healthy subjects remains nearly constant, with a transient +/-5% decrease in volume at end systole. This "constant-volume" attribute defines a constraint that the longitudinal versus radial pericardial contour dimension relationship must obey. Using cardiac MRI, we determined the extent to which the constant-volume attribute is valid from four-chamber slices (two-dimensional) compared with three-dimensional volumetric data. We also compared the relative percentage of longitudinal versus radial (short-axis) change in cross-sectional area (dimension) of the pericardial contour, thereby assessing the fate of the +/-5% end-systolic volume decrease. We analyzed images from 10 normal volunteers and 1 subject with congenital absence of the pericardium, obtained using a 1.5-T MR scanner. Short-axis cine loop stacks covering the entire heart were acquired, as were single four-chamber cine loops. In the short-axis and four-chamber slices, relative to midventricular end-diastolic location, end-systolic pericardial (left ventricular epicardial) displacement was observed to be radial and maximized at end systole. Longitudinal (apex to mediastinum) pericardial contour dimension change and pericardial area change on the four-chamber slice were negligible throughout the cardiac cycle. We conclude that the +/-5% end-systolic decrease in the volume encompassed by the pericardial sack is primarily accounted for by a "crescent effect" on short-axis views, manifesting as a nonisotropic radial diminution of the pericardial/epicardial contour of the left ventricle. This systolic drop in cardiac volume occurs primarily at the ventricular level and is made up during the subsequent diastole when blood crosses the pericardium in the pulmonary venous Doppler D wave during early rapid left ventricular filling.     

Dynamic simulation pericardial bioprosthetic heart valve function

While providing nearly trouble-free function for 10-12 years, current bioprosthetic heart valves (BHV) continue to suffer from limited long-term durability. This is usually a result of leaflet calcification and/or structural degeneration, which may be related to regions of stress concentration associated with complex leaflet deformations. In the current work, a dynamic three-dimensional finite element analysis of a pericardial BHV was performed with a recently developed FE implementation of the generalized nonlinear anisotropic Fung-type elastic constitutive model for pericardial BHV tissues (W. Sun and M.S. Sacks, 2005, [Biomech. Model. Mechanobiol., 4(2-3), pp. 190-199]). The pericardial BHV was subjected to time-varying physiological pressure loading to compute the deformation and stress distribution during the opening phase of the valve function. A dynamic sequence of the displacements revealed that the free edge of the leaflet reached the fully open position earlier and the belly region followed. Asymmetry was observed in the resulting displacement and stress distribution due to the fiber direction and the anisotropic characteristics of the Fung-type elastic constitutive material model. The computed stress distribution indicated relatively high magnitudes near the free edge of the leaflet with local bending deformation and subsequently at the leaflet attachment boundary. The maximum computed von Mises stress during the opening phase was 33.8 kPa. The dynamic analysis indicated that the free edge regions of the leaflets were subjected to significant flexural deformation that may potentially lead to structural degeneration after millions of cycles of valve function. The regions subjected to time varying flexural deformation and high stresses of the present study also correspond to regions of tissue valve calcification and structural failure reported from explanted valves. In addition, the present simulation also demonstrated the importance of including the bending component together with the in-plane material behavior of the leaflets towards physiologically realistic deformation of the leaflets. Dynamic simulations with experimentally determined leaflet material specification can be potentially used to modify the valve towards an optimal design to minimize regions of stress concentration and structural failure.     

去细胞牛颈静脉构建组织工程右心带瓣管道体内 实验初步研究

目的:将体外构建的组织工程右心带瓣管道,以带瓣补片的形式移植于犬主肺动脉,观测带瓣管道材料体内情况。方法:去细胞处理牛颈静脉体,无菌处理后种植标记过的犬骨髓间质干细胞,构建组织工程带瓣管道,犬开胸手术,将体外构建的组织工程右心带瓣管道,以带瓣补片的形式移植于犬主肺动脉,术后4、8、12行胸部B超检查;取出补片,HE染色;荧光显微镜下标记细胞检测;样本钙含量测定。结果:术后犬胸部B超观察:瓣叶无增厚,钙化,管道血流通畅,无血栓及钙化。术后4、8、12周除了瓣叶逐渐缩小外,补片无动脉瘤形成,瓣膜表面光滑,无血栓形成,弹性良好,血管壁内面光滑,无血栓形成。种植种子细胞牛颈静脉带瓣补片成活。4周钙含量增加,8周时候,钙含量又有增加,12周时钙含量与8周相比无明显变化。结论:组织工程技术构建组织工程右心带瓣管道有可行之处。     

Ablation of mitral annular and leaflet muscle: effects on annular and leaflet dynamics

Mitral annular (MA) and leaflet three-dimensional (3-D) dynamics were examined after circumferential phenol ablation of the MA and anterior mitral leaflet (AML) muscle. Radiopaque markers were sutured to the left ventricle, MA, and both mitral leaflets in 18 sheep. In 10 sheep, phenol was applied circumferentially to the atrial surface of the mitral annulus and the hinge region of the AML, whereas 8 sheep served as controls. Animals were studied with biplane video fluoroscopy for computation of 3-D mitral annular area (MAA) and leaflet shape. MAA contraction (MAACont) was determined from maximum to minimum value. Presystolic MAA (PS-MAACont) reduction was calculated as the percentage of total reduction occurring before end diastole. Phenol ablation decreased PS-MAACont (72 +/- 6 vs. 47 +/- 31%, P = 0.04) and delayed valve closure (31 +/- 11 vs. 57 +/- 25 ms, P = 0.017). In control, the AML had a compound sigmoid shape; after phenol, this shape was entirely concave to the atrium during valve closure. These data indicate that myocardial fibers on the atrial side of the valve influence the 3-D dynamic geometry and shape of the MA and AML.     

Prediction of stenting related adverse events through patient-specific finite element modelling

Right ventricular outflow tract (RVOT) calcific obstruction is frequent after homograft conduit implantation to treat congenital heart disease. Stenting and percutaneous pulmonary valve implantation (PPVI) can relieve the obstruction and prolong the conduit lifespan, but require accurate pre-procedural evaluation to minimize the risk of coronary artery (CA) compression, stent fracture, conduit injury or arterial distortion.Herein, we test patient-specific finite element (FE) modeling as a tool to assess stenting feasibility and investigate clinically relevant risks associated to the percutaneous intervention.Three patients undergoing attempted PPVI due to calcific RVOT conduit failure were enrolled; the calcific RVOT, the aortic root and the proximal CA were segmented on CT scans for each patient. We numerically reproduced RVOT balloon angioplasty to test procedure feasibility and the subsequent RVOT pre-stenting expanding the stent through a balloon-in-balloon delivery system.Our FE framework predicted the occurrence of CA compression in the patient excluded from the real procedure. In the two patients undergoing RVOT stenting, numerical results were consistent with intraprocedural in-vivo fluoroscopic evidences. Furthermore, it quantified the stresses on the stent and on the relevant native structures, highlighting their marked dependence on the extent, shape and location of the calcific deposits. Stent deployment induced displacement and mechanical loading of the calcific deposits, also impacting on the adjacent anatomical structures.This novel workflow has the potential to tackle the analysis of complex RVOT clinical scenarios, pinpointing the procedure impact on the dysfunctional anatomy and elucidating potential periprocedural complications.     

Culture of mesothelial cells from bovine pericardium and characterization of their arachidonate metabolism

Cultures of mesothelial cells from bovine pericardium were established and their arachidonate metabolism was characterized. The identification of the cultured cells was based on morphological observations, and by electrophoretic analysis of cytoskeletal proteins, which demonstrated a pattern previously reported for mesothelial cells. Factor VIII-related antigen was present by indirect immunofluorescence, but the cells had no thrombomodulin activity. The cultured pericardial cells metabolized arachidonic acid to 6-ketoprostaglandin F1 alpha and a small amount of prostaglandin E2. The same metabolites were produced by pieces of intact parietal pericardium but not by pieces from which mesothelium had been removed. The cultured mesothelial cells produced 94.6 +/- 60.4 (mean +/- S.D.) ng/mg (n = 3) cell protein of 6-ketoprostaglandin F1 alpha in response to the calcium ionophore A23187, 117.3 +/- 13.6 ng/mg (n = 3) with exogenous arachidonic acid, 18.3 +/- 11.3 ng/mg (n = 5) with bradykinin, 8.4 +/- 4.3 ng/kg (n = 4) with histamine and 11.2 +/- 9.7 ng/mg (n = 5) with thrombin. All of these values were significantly higher (P less than 0.05) than the control (2.1 +/- 1 ng/mg; n = 5). From these results, we conclude that the mesothelial cells account for the arachidonate metabolism in the pericardium. The production of prostaglandin I2 occurs in response to physiological or pathological, agonists, and is substantial. That is, it is approximately the same as endothelial cells. The release of eicosanoids by mesothelial cells into the pericardial space may have a significant role in cardiac physiology and pathology.     

Techniques of aortic valve repair

Similar to mitral repair, newer methods of aortic valve reconstruction are achieving excellent outcomes with an 85% to 90% freedom from valve-related complications at 10 years. The goal of this review is to illustrate these newer and more stable techniques of aortic valve repair. Most patients with aortic insufficiency from either trileaflet or bicuspid aortic valves are candidates for repair, in addition to selected patients with mixed aortic stenosis/insufficiency and aortic root aneurysms. Initially, aggressive commissural annuloplasty is performed to reduce measured valve diameter to 19 to 21 mm. Leaflet prolapse is corrected with plication stitches placed in the free edge of each leaflet adjacent to the Nodulus Arantius. In this regard, the leaflet free edge functions as the chorda tendinea of the aortic valve, and shortening with plication stitches raises the leaflet to a proper "effective height." Leaflet defects are augmented with gluteraldehyde-fixed autologous pericardium, and mild-to-moderate strategically placed spicules of calcium are removed with the cavitron ultrasonic surgical aspirator. Using these methods, most insufficient aortic valves, and many with mixed lesions, can be satisfactorily repaired. Six cases are illustrated in this review, spanning the spectrum of pathologies from annular dilatation without leaflet defects, to standard congenital bicuspid valve with prolapse, to trileaflet prolapse, to unusual bicuspid pathology with calcification, to a moderately calcified trileaflet valve with mixed lesions, and to aortic root aneurysms with severe aortic insufficiency. All valves were repaired using the techniques described above with trivial residual leak and minimal gradients. All repairs have been followed with yearly echocardiography, and valve reconstruction with these methods is now quite stable with excellent late outcomes. Most insufficient aortic valves now can undergo stable repair with minimal late valve-related complications. Greater application of aortic valve repair seems indicated.     

Uncommon acquired Gerbode defect following extensive bicuspid aortic valve endocarditis

Gerbode defect is a rare type of left ventricle to right atrium shunt. It is usually congenital in origin, but acquired cases are also described, mainly following infective endocarditis, valve replacement, trauma or acute myocardial infarction. We report a case of a 50-year-old man who suffered an extensive and complex infective endocarditis involving a bicuspid aortic valve, the mitral-aortic intervalvular fibrosa and the anterior leaflet of the mitral valve. After dual valve replacement and annular reconstruction, a shunt between the left ventricle and the right atrium - Gerbode defect, and a severe leak of the mitral prosthesis were detected. Reintervention was performed with successful shunt closure with an autologous pericardial patch and paravalvular leak correction. No major complications occurred denying the immediate post-surgery period and the follow-up at the first year was uneventful.     

Effect of cryoprotectants on hatching rate of red seabream (Pagrus major) embryos

The objectives were to investigate the effect of cryoprotectants on the hatching rate of red seabream embryos. Heart-beat embryos were immersed in: five permeable cryoprotectants, dimethyl sulfoxide (DMSO), glycerol (Gly), methanol (MeOH), 1,2-propylene glycol (PG), and ethylene glycol (EG), in concentrations of 5-30% for 10, 30, or 60min; and two non-permeable cryoprotectants: polyvinylpyrrolidone (PVP), and sucrose (in concentrations of 5-20% for 10 or 30min). The embryos were then washed and incubated in filtered seawater until hatching occurred. The hatching rate of the embryos treated with permeable cryoprotectants decreased (P<0.05) with increased concentration and duration of exposure. In addition, PG was the least toxic permeable cryoprotectant, followed by DMSO and EG, whereas Gly and MeOH were the most toxic. At a concentration of 15% and 30min exposure, the hatching rate of the embryos immersed in PG was 93.3+/-7.0% (mean+/-S.D.), however, in DMSO, EG, Gly, and MeOH, it was 82.7+/-10.4, 22.0+/-5.7, 0.0+/-0.0, and 0.0+/-0.0%, respectively. Hatching rate of embryos treated with PVP decreased (P<0.05) with the increase of concentration and exposure time, whereas for embryos treated with sucrose, there was no significant decrease in comparison with the control at the concentrations used.     

Tissue engineering lamb heart valve leaflets

Tissue engineered lamb heart valve leaflets (N - 3) were constructed by repeatedly seeding a concentrated suspension of autologous myofibroblasts onto a biodegradable synthetic polymeric scaffold composed of fibers made from polyglycolic acid and polylactic acid. Over a 2-week period the cells attached to the polymer fibers, multiplied, and formed a tissue core in the shape of the matrix. The tissue core was seeded with autologous large-vessel endothelial cells that formed a monolayer which coated the outer surface of the leaflet. The tissue engineered leaflets were surgically implanted in place of the right posterior pulmonary valve leaflet of the donor lamb while on cardiopulmonary bypass. Pulmonary valve function was evaluated by two-dimensional echocardiography with color Doppler which demonstrated valve function without evidence of stenosis and with only trivial regurgitation under normal physiologic conditions. Histologically, the tissue engineered heart valve leaflets resembled native valve leaflet tissue. (c) 1996 John Wiley & Sons, Inc.     

The flexural rigidity of the aortic valve leaflet in the commissural region

Flexure is a major deformation mode of the aortic valve (AV) leaflet, particularly in the commissural region where the upper portion of the leaflet joins the aortic root. However, there are no existing data known on the mechanical properties of leaflet in the commissural region. To address this issue, we quantified the effective stiffness of the commissural region using a cantilever beam method. Ten specimens were prepared, with each specimen flexed in the direction of natural leaflet motion (forward) and against the natural motion (reverse). At a flexure angle (phi) of 30 degrees , the effective forward direction modulus E was 42.63+/-4.44 kPa and the reverse direction E was 75.01+/-14.53 kPa (p=0.049). Further, E-phi response was linear (r(2) approximately 0.9) in both flexural directions. Values for dE/dphi were -2.24+/-0.6 kPa/ degrees and -1.90+/-0.3 kPa/ degrees in the forward and reverse directions, respectively (not statistically different, p=0.424), indicating a consistent decrease in stiffness with increased flexure. In comparison, we have reported that the effective tissue stiffness of AV leaflet belly region was 150-200 kPa [Merryman, W.D., Huang, H.Y.S., Schoen, F.J., Sacks, M.S. (2006). The effects of cellular contraction on AV leaflet flexural stiffness. Journal of Biomechanics 39 (1), 88-96], which was also independent of direction and amount of flexure. Histological studies of the commissure region indicated that tissue buckling was a probable mechanism for decrease in E with increasing flexure. The observed change in E with flexural angle in the commissural region is a subtle aspect of valve function. From a valve design perspective, these findings can be used as design criteria in fabricating prosthetic devices AV resulting in better functional performance.     

Assessment and consequences of the constant-volume attribute of the four-chambered heart

The constant-volume hypothesis regarding the four-chambered heart states that total pericardial volume remains invariant throughout the cardiac cycle. Previous canine studies have indicated that the pericardial volume remains constant within 5%; however, this hypothesis has not been validated in humans using state-of-the-art technology. The constant-volume hypothesis has several predictable functional consequences, including a relationship between atrial ejection fraction and chamber equilibrium volumes. Using cardiac magnetic resonance (MR) imaging (MRI), we measured the extent to which the constant-volume attribute of the heart is valid, and we tested the accuracy of the predicted relationship between atrial ejection fraction and chamber equilibrium volumes. Eleven normal volunteers and one volunteer with congenital absence of the pericardium were imaged using a 1.5-T MR scanner. A short-axis cine-loop stack covering the entire heart was acquired. The cardiac cycle was divided into 20 intervals. For each slice and interval, pericardial volumes were measured. The slices were stacked and summed, and total pericardial volume as a function of time was determined for each subject. In the normal subjects, chamber volumes at ventricular end diastole, end systole, and diastasis were measured. Pericardial volume remained invariant within 5 +/- 1% in normal subjects; maximum variation occurred near end systole. In the subject with congenital absence of the pericardium, total heart volume, defined by the epicardial surface, varied by 12%. The predictions of the relationship between atrial ejection fraction and chamber equilibrium volumes were well fit by MRI data. In normal subjects, the four-chambered heart is a constant-volume pump within 5 +/- 1%, and constant-volume-based modeling accurately predicts previously unreported physiological relationships.