Structure and torsion of the normal and situs inversus totalis cardiac left ventricle. I. Experimental data in humans

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.     

Role of tissue structure on ventricular wall mechanics

It is well known that systolic wall thickening in the inner half of the left ventricular (LV) wall is of greater magnitude than predicted by myofiber contraction alone. Previous studies have related the deformation of the LV wall to the orientation of the laminar architecture. Using this method, wall thickening can be interpreted as the sum of contributions due to extension, thickening, and shearing of the laminar sheets. We hypothesized that the thickening mechanics of the ventricular wall are determined by the structural organization of the underlying tissue, and may not be influenced by factors such as loading and activation sequence. To test this hypothesis, we calculated finite strains from biplane cineradiography of transmural markers implanted in apical (n = 22) and basal (n = 12) regions of the canine anterior LV free wall. Strains were referred to three-dimensional laminar microstructural axes measured by histology. The results indicate that sheet angle is of opposite sign in the apical and basal regions, but absolute value differs only in the subepicardium. During systole, shearing and extension of the laminae contribute the most to wall thickening, accounting for >90% (transmural average) at both apex and base. These two types of deformation are also most prominent during diastolic inflation. Increasing afterload has no effect on the pattern of systolic wall thickening, nor does reversing transmural activation sequence. The pattern of wall thickening appears to be a function of the orientation of the laminar sheets, which vary regionally and transmurally. Thus, acute interventions do not appear to alter the contributions of the laminae to wall thickening, providing further evidence that the structural architecture of the ventricular wall is the dominant factor for its regional mechanical function.     

Why SIT Works: Normal Function Despite Typical Myofiber Pattern in Situs Inversus Totalis (SIT) Hearts Derived by Shear-induced Myofiber Reorientation

The left ventricle (LV) of mammals with Situs Solitus (SS, normal organ arrangement) displays hardly any interindividual variation in myofiber pattern and experimentally determined torsion. SS LV myofiber pattern has been suggested to result from adaptive myofiber reorientation, in turn leading to efficient pump and myofiber function. Limited data from the Situs Inversus Totalis (SIT, a complete mirror image of organ anatomy and position) LV demonstrated an essential different myofiber pattern, being normal at the apex but mirrored at the base. Considerable differences in torsion patterns in between human SIT LVs even suggest variation in myofiber pattern among SIT LVs themselves. We addressed whether different myofiber patterns in the SIT LV can be predicted by adaptive myofiber reorientation and whether they yield similar pump and myofiber function as in the SS LV. With a mathematical model of LV mechanics including shear induced myofiber reorientation, we predicted myofiber patterns of one SS and three different SIT LVs. Initial conditions for SIT were based on scarce information on the helix angle. The transverse angle was set to zero. During reorientation, a non-zero transverse angle developed, pump function increased, and myofiber function increased and became more homogeneous. Three continuous SIT structures emerged with a different location of transition between normal and mirrored myofiber orientation pattern. Predicted SIT torsion patterns matched experimentally determined ones. Pump and myofiber function in SIT and SS LVs are similar, despite essential differences in myocardial structure. SS and SIT LV structure and function may originate from same processes of adaptive myofiber reorientation.     

Transmural mechanics at left ventricular epicardial pacing site

Left ventricular (LV) epicardial pacing acutely reduces wall thickening at the pacing site. Because LV epicardial pacing also reduces transverse shear deformation, which is related to myocardial sheet shear, we hypothesized that impaired end-systolic wall thickening at the pacing site is due to reduction in myocardial sheet shear deformation, resulting in a reduced contribution of sheet shear to wall thickening. We also hypothesized that epicardial pacing would reverse the transmural mechanical activation sequence and thereby mitigate normal transmural deformation. To test these hypotheses, we investigated the effects of LV epicardial pacing on transmural fiber-sheet mechanics by determining three-dimensional finite deformation during normal atrioventricular conduction and LV epicardial pacing in the anterior wall of normal dog hearts in vivo. Our measurements indicate that impaired end-systolic wall thickening at the pacing site was not due to selective reduction of sheet shear, but rather resulted from overall depression of fiber-sheet deformation, and relative contributions of sheet strains to wall thickening were maintained. These findings suggest lack of effective end-systolic myocardial deformation at the pacing site, most likely because the pacing site initiates contraction significantly earlier than the rest of the ventricle. Epicardial pacing also induced reversal of the transmural mechanical activation sequence, which depressed sheet extension and wall thickening early in the cardiac cycle, whereas transverse shear and sheet shear deformation were not affected. These findings suggest that normal sheet extension and wall thickening immediately after activation may require normal transmural activation sequence, whereas sheet shear deformation may be determined by local anatomy.     

An elongation model of left ventricle deformation in diastole

A numerical method of the left ventricle (LV) deformation, an elongation model, was put forth for the study of LV fluid mechanics in diastole. The LV elongated only along the apical axis, and the motion was controlled by the intraventricular flow rate. Two other LV models, a fixed control volume model and a dilation model, were also used for model comparison and the study of LV fluid mechanics. For clinical sphere indices (SIs, between 1.0 and 2.0), the three models showed little difference in pressure and velocity distributions along the apical axis at E-peak. The energy dissipation was lower at a larger SI in that the jet and vortex development was less limited by the LV cavity in the apical direction. LV deformation of apical elongation may represent the primary feature of LV deformation in comparison with the secondary radial expansion. The elongation model of the LV deformation with an appropriate SI is a reasonable, simple method to study LV fluid mechanics in diastole.     

Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure

To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 +/- 2 wk (means +/- SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 +/- 0.030; P <0.05), whereas the apical site did not [P=not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 +/- 0.003 at 2 wk and 0.054 +/- 0.021 at final; both P <0.05), which contributed to a significant increase in wall thickness at the final study (0.181 +/- 0.047; P < 0.05), whereas the apical site did not (P=NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.     

A finite element model of the human left ventricular systole

Local wall stress is the pivotal determinant of the heart muscle's systolic function. Under in vivo conditions, however, such stresses cannot be measured systematically and quantitatively. In contrast, imaging techniques based on magnetic resonance (MR) allow the determination of the deformation pattern of the left ventricle (LV) in vivo with high accuracy. The question arises to what extent deformation measurements are significant and might provide a possibility for future diagnostic purposes. The contractile forces cause deformation of LV myocardial tissue in terms of wall thickening, longitudinal shortening, twisting rotation and radial constriction. The myocardium is thereby understood to act as a densely interlaced mesh. Yet, whole cycle image sequences display a distribution of wall strains as function of space and time heralding a significant amount of inhomogeneity even under healthy conditions. We made similar observations previously by direct measurement of local contractile activity. The major reasons for these inhomogeneities derive from regional deviations of the ventricular walls from an ideal spheroidal shape along with marked disparities in focal fibre orientation. In response to a lack of diagnostic tools able to measure wall stress in clinical routine, this communication is aimed at an analysis and functional interpretation of the deformation pattern of an exemplary human heart at end-systole. To this end, the finite element (FE) method was used to simulate the three-dimensional deformations of the left ventricular myocardium due to contractile fibre forces at end-systole. The anisotropy associated with the fibre structure of the myocardial tissue was included in the form of a fibre orientation vector field which was reconstructed from the measured fibre trajectories in a post mortem human heart. Contraction was modelled by an additive second Piola-Kirchhoff active stress tensor. As a first conclusion, it became evident that longitudinal fibre forces, cross-fibre forces and shear along with systolic fibre rearrangement have to be taken into account for a useful modelling of systolic deformation. Second, a realistic geometry and fibre architecture lead to typical and substantially inhomogeneous deformation patterns as they are recorded in real hearts. We therefore, expect that the measurement of systolic deformation might provide useful diagnostic information.     

Description of the deformation of the left ventricle by a kinematic model.

A model of left ventricular (LV) kinematics is essential to identify the fundamental physiological modes of LV deformation during a complete cardiac cycle as observed from the motion of a finite number of markers embedded in the LV wall. Kinematics can be described by a number of modes of motion and deformation in succession. An obvious mode of LV deformation is the ejection of cavity volume while the wall thickens. In the more sophisticated model of LV kinematics developed here, seven time-dependent parameters were used to describe not only volume change but also torsion and shape changes throughout the cardiac cycle. Rigid-body motion required another six parameters. The kinematic model employed a deformation field that had no singularities within the myocardium, and all parameters describing the modes of deformation were dimensionless. Note that torsion, volume and symmetric shape changes all require the definition of a cardiac coordinate system, which has generally been related to the measured cardiac geometry by reference to approximate anatomical landmarks. However, in the present study the coordinate system was positioned objectively by a least-squares fit of the kinematic model to the measured motion of markers. Theoretically, at least five markers are needed to find a unique set of parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

A finite element model of the human left ventricular systole

Local wall stress is the pivotal determinant of the heart muscle's systolic function. Under in vivo conditions, however, such stresses cannot be measured systematically and quantitatively. In contrast, imaging techniques based on magnetic resonance (MR) allow the determination of the deformation pattern of the left ventricle (LV) in vivo with high accuracy. The question arises to what extent deformation measurements are significant and might provide a possibility for future diagnostic purposes.

The contractile forces cause deformation of LV myocardial tissue in terms of wall thickening, longitudinal shortening, twisting rotation and radial constriction. The myocardium is thereby understood to act as a densely interlaced mesh. Yet, whole cycle image sequences display a distribution of wall strains as function of space and time heralding a significant amount of inhomogeneity even under healthy conditions. We made similar observations previously by direct measurement of local contractile activity. The major reasons for these inhomogeneities derive from regional deviations of the ventricular walls from an ideal spheroidal shape along with marked disparities in focal fibre orientation.

In response to a lack of diagnostic tools able to measure wall stress in clinical routine, this communication is aimed at an analysis and functional interpretation of the deformation pattern of an exemplary human heart at end-systole. To this end, the finite element (FE) method was used to simulate the three-dimensional deformations of the left ventricular myocardium due to contractile fibre forces at end-systole. The anisotropy associated with the fibre structure of the myocardial tissue was included in the form of a fibre orientation vector field which was reconstructed from the measured fibre trajectories in a post mortem human heart. Contraction was modelled by an additive second Piola–Kirchhoff active stress tensor.

As a first conclusion, it became evident that longitudinal fibre forces, cross-fibre forces and shear along with systolic fibre rearrangement have to be taken into account for a useful modelling of systolic deformation. Second, a realistic geometry and fibre architecture lead to typical and substantially inhomogeneous deformation patterns as they are recorded in real hearts. We therefore, expect that the measurement of systolic deformation might provide useful diagnostic information.     

Beyond apical ballooning: computational modelling reveals morphological features of Takotsubo cardiomyopathy

Abstract

Takotsubo cardiomyopathy (TCM) is characterized by transient myocardial dysfunction, typically at the left ventricular (LV) apex. Its pathophysiology and recovery mechanisms remain unknown. We investigated LV morphology and deformation in n?=?28 TCM patients. Patients with MRI within 5?days from admission (“early TCM”) showed reduced LVEF and higher ventricular volumes, but no differences in ECG, global strains or myocardial oedema. Statistical shape modelling described LV size (Mode 1), apical sphericity (Mode 2) and height (Mode 3). Significant differences in Mode 1 suggest that “early TCM” LV remodeling is mainly influenced by a change in ventricular size rather than apical sphericity.     

ONTOGENETIC STUDY OF FLORAL ORGANS OF PEACH (PRUNUS PERSICA) UTILIZING CYTOCHIMERAL PLANTS

Cell lineages were followed throughout floral ontogeny in cytochimeral peaches [Prunus persica (L.) Batsch] by observations of chromosome number and nuclear size. The contribution of the three apical cell layers to the organs of the flowers was determined. In addition to the epidermal tissue, L-I produced several layers of cells at the suture of the ovary wall, seven or eight cell layers of the nucellus at the micropylar end of the ovule, and almost all of the integuments. L-II gave rise to extensive internal tissue in the calyx and corolla tubes and to all internal tissue of the petal, anther, and ovule except for a small region at the base of the latter two organs. L-III contributed significantly only to the central region of the calyx and corolla tubes and the ovary wall. A single apical layer gave rise to several different tissues, and at times a single tissue was made up of cells from 1–3 different apical layers. Within the limits imposed by their genotype the final form of differentiated cells was determined by their position in the mature organ and not by the apical layer from which they were derived. The corolla tube was shown to be a single structure, congenitally fused, and the ovary to be ontogenetically fused at the suture.     

Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes

The biophysical characteristics and alpha subunits underlying calcium-independent transient outward potassium current (Ito) phenotypes expressed in ferret left ventricular epicardial (LV epi) and endocardial (LV endo) myocytes were analyzed using patch clamp, fluorescent in situ hybridization (FISH), and immunofluorescent (IF) techniques. Two distinct Ito phenotypes were measured (21-22 degrees C) in the majority of LV epi and LV endo myocytes studied. The two Ito phenotypes displayed marked differences in peak current densities, activation thresholds, inactivation characteristics, and recovery kinetics. Ito,epi recovered rapidly [taurec, -70 mV = 51 +/- 3 ms] with minimal cumulative inactivation, while Ito,endo recovered slowly [taurec, -70 mV = 3,002 +/- 447 ms] with marked cumulative inactivation. Heteropoda toxin 2 (150 nM) blocked Ito,epi in a voltage-dependent manner, but had no effect on Ito,endo. Parallel FISH and IF measurements conducted on isolated LV epi and LV endo myocytes demonstrated that Kv1.4, Kv4.2, and Kv4.3 alpha subunit expression in LV myocyte types was quite heterogenous: (a) Kv4.2 and Kv4.3 were more predominantly expressed in LV epi than LV endo myocytes, and (b) Kv1.4 was expressed in the majority of LV endo myocytes but was essentially absent in LV epi myocytes. In combination with previous measurements on recovery kinetics (Kv1.4, slow; Kv4.2/4.3, relatively rapid) and Heteropoda toxin block (Kv1.4, insensitive; Kv4.2, sensitive), our results strongly support the hypothesis that, in ferret heart, Kv4.2/Kv4.3 and Kv1.4 alpha subunits, respectively, are the molecular substrates underlying the Ito,epi and Ito,endo phenotypes. FISH and IF measurements were also conducted on ferret ventricular tissue sections. The three Ito alpha subunits again showed distinct patterns of distribution: (a) Kv1.4 was localized primarily to the apical portion of the LV septum, LV endocardium, and approximate inner 75% of the LV free wall; (b) Kv4. 2 was localized primarily to the right ventricular free wall, epicardial layers of the LV, and base of the heart; and (c) Kv4.3 was localized primarily to epicardial layers of the LV apex and diffusely distributed in the LV free wall and septum. Therefore, in intact ventricular tissue, a heterogeneous distribution of candidate Ito alpha subunits not only exists from LV epicardium to endocardium but also from apex to base.     

Mammoth interatrial septal aneurysm in the ICE age

Background

Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon.

Case Presentation

A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM) was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II), but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest); and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient), but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death.

Conclusion

Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM).     

Three-dimensional systolic kinematics of the right ventricle

The right ventricle (RV) of the heart is responsible for pumping blood to the lungs. Its kinematics are not as well understood as that of the left ventricle (LV) due to its thin wall and asymmetric geometry. In this study, the combination of tagged MRI and three-dimensional (3-D) image-processing techniques was used to reconstruct 3-D RV-LV motion and deformation. The reconstructed models were used to quantify the 3-D global and local deformation of the ventricles in a set of normal subjects. When compared with the LV, the RV exhibited a similar twisting pattern, a more longitudinal strain pattern, and a greater amount of displacement.     

Early calcification patterns of the iliac arteries and their relation to the arterial structure

Summary Gross calcifications of the common iliac and internal iliac arteries represent a common finding in newborn children and infants. In both arteries, the calcific deposits regularly appear in certain areas of the arterial luminal surface only, whereas the other parts of the arterial wall remain free of gross lesions even in cases with a pronounced calcification. In the common iliac artery, the lateral wall of the vessel and the adjacent sectors of the anterior and posterior wall represent the predilection site of calcific deposits. In the internal iliac artery, the gross calcifications have been regularly demonstrated in the dorso-medial wall. The predominant localisation of the calcification in these parts of the vessels and its absence in the others depend on the definite structural features of the arterial tube and different affinity for calcium of the individual structural elements. In both iliac arteries, only the primary internal elastic membrane undergoes early calcification. However, unlike the most muscular arteries, this membrane is not developed in the whole arterial circumference of the common iliac and internal iliac arteries, but is absent in large areas of their arterial luminal layer. In these areas, the subendothelial or subintimal elastic layers are formed by the networks of longitudinally arranged elastic fibers or membraneous elastic structures which arise from the elastic networks with the further growth. These elastic elements always stay free of calcific deposits. The structural features found in both iliac arteries may be important for the development of the later pathological changes.     

Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation

Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.     

Transmural left ventricular mechanics underlying torsional recoil during relaxation

Early relaxation in the cardiac cycle is characterized by rapid torsional recoil of the left ventricular (LV) wall. To elucidate the contribution of the transmural arrangement of the myofiber to relaxation, we determined the time course of three-dimensional fiber-sheet strains in the anterior wall of five adult mongrel dogs in vivo during early relaxation with biplane cineangiography (125 Hz) of implanted transmural markers. Fiber-sheet strains were found from transmural fiber and sheet orientations directly measured in the heart tissue. The strain time course was determined during early relaxation in the epicardial, midwall, and endocardial layers referenced to the end-diastolic configuration. During early relaxation, significant circumferential stretch, wall thinning, and in-plane and transverse shear were observed (P < 0.05). We also observed significant stretch along myofibers in the epicardial layers and sheet shortening and shear in the endocardial layers (P < 0.01). Importantly, predominant epicardial stretch along the fiber direction and endocardial sheet shortening occurred during isovolumic relaxation (P < 0.05). We conclude that the LV mechanics during early relaxation involves substantial deformation of fiber and sheet structures with significant transmural heterogeneity. Predominant epicardial stretch along myofibers during isovolumic relaxation appears to drive global torsional recoil to aid early diastolic filling.     

Transmural differences in respiratory capacity across the rat left ventricle in health, aging, and streptozotocin-induced diabetes mellitus: evidence that mitochondrial dysfunction begins in the subepicardium

In diabetic cardiomyopathy, ventricular dysfunction occurs in the absence of hypertension or atherosclerosis and is accompanied by altered myocardial substrate utilization and depressed mitochondrial respiration. It is not known if mitochondrial function differs across the left ventricular (LV) wall in diabetes. In the healthy heart, the inner subendocardial region demonstrates higher rates of blood flow, oxygen consumption, and ATP turnover compared with the outer subepicardial region, but published transmural respirometric measurements have not demonstrated differences. We aim to measure mitochondrial function in Wistar rat LV to determine the effects of age, streptozotocin-diabetes, and LV layer. High-resolution respirometry measured indexes of respiration in saponin-skinned fibers dissected from the LV subendocardium and subepicardium of 3-mo-old rats after 1 mo of streptozotocin-induced diabetes and 4-mo-old rats following 2 mo of diabetes. Heart rate and heartbeat duration were measured under isoflurane-anesthesia using a fetal-Doppler, and transmission electron microscopy was employed to observe ultrastructural differences. Heart rate decreased with age and diabetes, whereas heartbeat duration increased with diabetes. While there were no transmural respirational differences in young healthy rat hearts, both myocardial layers showed a respiratory depression with age (30-40%). In 1-mo diabetic rat hearts only subepicardial respiration was depressed, whereas after 2 mo diabetes, respiration in subendocardial and subepicardial layers was depressed and showed elevated leak (state 2) respiration. These data provide evidence that mitochondrial dysfunction is first detectable in the subepicardium of diabetic rat LV, whereas there are measureable changes in LV mitochondria after only 4 mo of aging.     

Postsystolic shortening of ischemic myocardium: a mechanism of abnormal intraventricular filling

Acute myocardial ischemia has been associated with abnormal filling patterns in the left ventricular (LV) apex. We hypothesized that this may in part be due to postsystolic shortening of ischemic apical segments, which leads to reversal of early diastolic apical flow. Fourteen open-chest anesthetized dogs were instrumented with micromanometers in the LV apex and left atrium and myocardial sonomicrometers in the anterior apical LV wall. Intraventricular filling by color Doppler and wall motion by strain Doppler echocardiography (SDE) were assessed from an apical view. Measurements were taken before and after 5 min of left anterior descending coronary artery (LAD) occlusion. In four dogs, we measured the pressure difference between the LV apex and outflow tract. At baseline, peak early diastolic flow velocities in the distal one-third of the LV were directed toward apex (9.2 +/- 1.6 cm/s). After LAD occlusion, the velocities reversed (-2.3 +/- 0.4 cm/s, P < 0.01), indicating that blood was ejected from the apex toward the base during early filling. This interpretation was confirmed by wall motion analysis, which showed postsystolic shortening of apical myocardial segments. The postsystolic shortening represented 9.7 +/- 1.7% (P < 0.01) and 14.2 +/- 2.4% (P < 0.01) of end-diastolic segment length by SDE and sonomicrometry, respectively. Consistent with the velocity changes, we found reversal of the early diastolic pressure gradient from the LV apex to outflow tract. In the present model, acute LAD occlusion resulted in reversal of early diastolic apical flow, and this was attributed to postsystolic shortening of dyskinetic apical segments. The clinical diagnostic importance of this finding remains to be determined.