Transmural distribution of three-dimensional systolic strains in stunned myocardium.

BACKGROUND: Regional function in stunned myocardium is usually thought to be more depressed in the endocardium than the epicardium. This has been attributed to the greater loss of blood flow at the endocardium during ischemia. METHODS AND RESULTS: We measured transmural distributions of 3D systolic strains relative to local myofiber axes in open-chest anesthetized dogs before 15 minutes of left anterior descending coronary artery occlusion and during 2 hours of reperfusion. During ischemia, regional myocardial blood flow was reduced 84% at the endocardium and 32% at the epicardium (P<0.005, n=7), but changes in end-systolic fiber length from baseline were transmurally uniform. Relative to baseline, radial segments in stunned tissue were significantly thinner at the endocardium than the epicardium at end systole (24+/-5% versus 16+/-3%; P<0.05, n=8), consistent with previous reports. Unlike radial and cross-fiber segments, however, the increase of end-systolic fiber lengths in stunned myocardium had no significant transmural gradient (23+/-8% epicardium versus 21+/-4% endocardium). We also observed significant 3D diastolic dysfunction in the ischemic-reperfused region transmurally. CONCLUSIONS: Myocardial ischemia/reperfusion in the dog results in a significant transmural gradient of dysfunction between epicardial and endocardial layers in radial and cross-fiber segments, but not for fiber segments, despite a gradient in blood flow reduction during ischemia. Perhaps systolic fiber dysfunction rather than the degree of perfusion deficit during the preceding ischemic period may be the main determinant of myocardial dysfunction during reperfusion.

Relating myocardial laminar architecture to shear strain and muscle fiber orientation.

Cardiac myofibers are organized into laminar sheets about four cells thick. Recently, it has been suggested that these layers coincide with the plane of maximum shear during systole. In general, there are two such planes, which are oriented at +/-45 degrees to the main principal strain axes. These planes do not necessarily contain the fiber axis. In the present study, we explicitly added the constraint that the sheet planes should also contain the muscle fiber axis. In a mathematical analysis of previously measured three-dimensional transmural systolic strain distributions in six dogs, we computed the planes of maximum shear, adding the latter constraint by using the also-measured muscle fiber axis. Generally, for such planes two solutions were found, suggesting that two populations of sheet orientation may exist. The angles at which the predicted sheets intersected transmural tissue slices, cut along left ventricular short- or long-axis planes, were strikingly similar to experimentally measured values. In conclusion, sheets coincide with planes of maximum systolic shear subject to the constraint that the muscle fiber axis is contained in this plane. Sheet orientation is not a unique function of the transmural location but occurs in two distinct populations.

Structural basis of regional dysfunction in acutely ischemic myocardium.

OBJECTIVE: Impaired systolic function in the normally perfused myocardium adjacent to an ischemic region - the functional border zone - is thought to result from mechanical interactions across the perfusion boundary. We investigated how segment orientation and vessel involved affect regional strains in the functional border zone and whether altered stresses associated with a step transition in contractility can explain the functional border zone. METHODS AND RESULTS: Regional epicardial strain distributions were obtained from measured displacements of radiopaque markers in open-chest anesthetized canines, and related to local myofiber angles and blood flows. The functional border zone for fiber strain was significantly narrower than that for cross-fiber strain and significantly wider for left anterior descending (LAD) than left circumflex (LCx) coronary occlusion (1.23 vs. 0.45 cm). A detailed three-dimensional computational model with a one-to-one relation between perfusion and myofilament activation and no transitional zone of intermediate contractility showed close agreement with these observations and significantly elevated stresses in the border zone. Differences between LAD and LCx occlusions in the model were due to differences in left ventricular systolic pressure and not to differences in perfusion boundary or muscle fiber orientation. The border zone was narrower for fiber strain than cross-fiber strain because systolic stiffness is greatest along the muscle fiber direction. CONCLUSION: Abnormal regional mechanics in the acute ischemic border arise from increased wall stresses without a transitional zone of intermediate contractility. Perfusion is more tightly coupled to fiber than cross-fiber strain, and a wider functional border zone of fiber strain during LAD than LCx occlusion is primarily due to higher regional wall stresses rather than anatomic variations.

Regional dysfunction correlates with myofiber disarray in transgenic mice with ventricular expression of ras.

A hallmark of certain cardiac diseases such as familial hypertrophic cardiomyopathy is focal myofiber disarray. Regional ventricular dysfunction occurs in human subjects with hypertrophic cardiomyopathy; however, no direct evidence exists to correlate regional dysfunction with myofiber disarray. We used a transgenic mouse, which exhibits regional myofiber disarray via ventricular expression of the human oncogene ras, to investigate the relationship between myofiber disarray and septal surface strain. An isolated ejecting mouse heart preparation was used to record deformation of markers on the septal surface and to determine nonhomogeneous septal surface strain maps. Myofiber disarray made in histological tissue sections was correlated with gradients in surface systolic shortening. Significantly smaller maximum principal shortening was associated with disarray located near the right ventricle (RV) septal surface. There was also significantly smaller surface shear strain associated with disarray located either near the RV surface or at the midwall. Because surface shear is a local indicator of torsion, we conclude that myofiber disarray is associated with reduced septal torsion and reduced surface shortening.

Structural and mechanical factors influencing infarct scar collagen organization.

Although large collagen fibers in myocardial infarct scar are highly organized, little is known about mechanisms controlling this organization. The preexisting extracellular matrix may act as a scaffold along which fibroblasts migrate. Conversely, deformation within the ischemic area could guide fibroblasts so new collagen is oriented to counteract the stretch. To investigate these potential mechanisms, we infarcted three groups of pigs. Group 1 served as infarct controls. Group 2 had the endocardium slit longitudinally to alter local systolic deformation. Group 3 had a plug sectioned from ischemic tissue and rotated 90 degrees. The slit altered systolic deformation in the infarcted tissue, changing circumferential strain from expansion to compression and increasing radial strain and shears and the variability of collagen fiber angles but not the mean angle. In the plug pigs, when deformation, matrix orientation, and continuity are altered in the infarct area, the result is complete disarray in the organization of collagen within the infarct scar.

Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium.

Previous studies suggest that the laminar architecture of left ventricular myocardium may be critical for normal ventricular mechanics. However, systolic three-dimensional deformation of the laminae has never been measured. Therefore, end-systolic finite strains relative to end diastole, from biplane radiography of transmural markers near the apex and base of the anesthetized open-chest canine anterior left ventricular free wall (n = 6), were referred to three-dimensional laminar microstructural axes reconstructed from histology. Whereas fiber shortening was uniform [-0.07 +/- 0.04 (SD)], radial wall thickening increased from base (0. 10 +/- 0.09) to apex (0.14 +/- 0.13). Extension of the laminae transverse to the muscle fibers also increased from base (0.08 +/- 0. 07) to apex (0.11 +/- 0.08), and interlaminar shear changed sign [0. 05 +/- 0.07 (base) and -0.07 +/- 0.09 (apex)], reflecting variations in laminar architecture. Nevertheless, the apex and base were similar in that at each site laminar extension and shear contributed approximately 60 and 40%, respectively, of mean transmural thickening. Kinematic considerations suggest that these dual wall-thickening mechanisms may have distinct ultrastructural origins.

Automated measurement of myofiber disarray in transgenic mice with ventricular expression of ras.

Quantitative assessment of myofiber disarray associated with diseases such as familial hypertrophic cardiomyopathy (FHC) can be performed by estimating local angular deviation of fiber orientation in histologic sections. The large number of measurements required to estimate angular deviation prohibits manual measurement. We describe methods for automated measurement of local orientation and angular deviation in tissue sections from transgenic mice with ventricular expression of ras, proposed as a model of FHC. Images of histologic tissue sections from normal and transgenic mice were analyzed using image processing techniques to estimate local orientation of myofibers. Results from the automated methods were compared with manual measurements. Automated methods estimated differing mean orientation in 7-20% of normal sections and 17-29% of transgenic tissue sections with differing dispersions in 23-30% of normal sections and 25% of transgenic tissue sections. Automated methods estimate 24.47+/-13.03% of total ventricular mass affected by disarray that is comparable to a previous estimate of 21.7% in the same mouse model. Automated methods are a rapid and accurate alternative to manual measurement for estimation of mean orientation and angular deviation in myocardial tissue sections. Differences between manual and automated methods may be attributed to the substantially larger number of measurements made by automated methods. Automated methods are particularly appropriate for use in determining local variation in orientation such as focal myofiber disarray associated with FHC. The generality of these methods suggests they may have use in other biological fields such as quantifying cellular alignment.

Protection against myocardial dysfunction after a brief ischemic period in transgenic mice expressing inducible heat shock protein 70.

Brief ischemic periods lead to myocardial dysfunction without myocardial infarction. It has been shown that expression of inducible HSP70 in hearts of transgenic mice leads to decreased infarct size, but it remains unclear if HSP70 can also protect against myocardial dysfunction after brief ischemia. To investigate this question, we developed a mouse model in which regional myocardial function can be measured before and after a temporary ischemic event in vivo. In addition, myocardial function was determined after brief episodes of global ischemia in an isolated Langendorff heart. HSP70-positive mice and transgene negative littermates underwent 8 min of regional myocardial ischemia created by occlusion of the left descending coronary artery, followed by 60 min of reperfusion. This procedure did not result in a myocardial infarction. Regional epicardial strain was used as a sensitive indicator for changes in myocardial function after cardiac ischemia. Maximum principal strain was significantly greater in HSP70-positive mice with 88+/-6% of preischemic values vs. 58+/-6% in transgene-negative mice (P < 0.05). Similarly, in isolated Langendorff perfused hearts of HSP70-positive and transgene-negative littermates exposed to 10 min of global ischemia and 90 min of reperfusion, HSP70 transgenic hearts showed a better-preserved ventricular peak systolic pressure. Thus, we conclude that expression of HSP70 protects against postischemic myocardial dysfunction as shown by better preserved myocardial function.

Functional implications of myocardial scar structure.

During healing after myocardial infarction, scar collagen content and stiffness do not correlate. We studied regional mechanics and both area fraction and orientation of large collagen fibers 3 wk after coronary ligation in the pig. During passive inflation of isolated, arrested hearts, the scar tissue demonstrated significantly less circumferential strain but similar longitudinal and radial deformation in comparison with noninfarcted regions of the same hearts. The observed selective resistance to circumferential deformation was consistent with the finding that most of the large collagen fibers in the scar were oriented within 30 degrees of the local circumferential axis. Furthermore, data from a previous study indicate that during ventricular systole these scars resist circumferential stretching, whereas they deform similarly to noninfarcted myocardium in the longitudinal and radial directions. We conclude that large collagen fiber structure is an important determinant of scar mechanical properties and that scar anisotropy allows the scar to resist circumferential stretching while deforming compatibly with adjacent noninfarcted myocardium in the longitudinal and radial directions.

Relationship between passive tissue strain and collagen uncoiling during healing of infarcted myocardium.

OBJECTIVE: The structure of the collagen scar during healing of a myocardial infarction is a determinant of the function of the remodeled tissue. We hypothesize that the passive deformations of both scar and normal tissue are related to the underlying collagen uncoiling as the tissue stretches, and that the unloaded tortuosity of the collagen may be a determinant of tissue stiffness at low ventricular pressure. Hence collagen uncoiling and tissue strain were measured during passive loading in normal tissue, and in healing infarct tissue. METHODS: Left ventricles of rats were infarcted by ligation of the left anterior descending artery for 2 weeks. Surface strains were measured during passive inflation in the scar region in one set of excised hearts, and other arrested hearts were fixed at different ventricular pressures, after which collagen tortuosity was measured in the infarcted and normal tissue. RESULTS: Passive loading strains were smaller in the scar in both the fiber and cross-fiber directions. Tortuosity decreased with load in normal and infarcted tissue, with fibrils tending to straighten more in the scar tissue at higher pressures (1.056 +/- 0.009 vs. 1.024 +/- 0.009 at P = 20 mmHg) with similar tortuosities at zero pressure (1.110 +/- 0.012 vs. 1.098 +/- 0.019). The decrease in tortuosity with strain was greater for the infarcted tissue. CONCLUSIONS: The greater stiffness of infarcted tissue at low pressure is not due to 'straightened' collagen fibers, and there may be a different three-dimensional structure of infarct vs. normal coiled collagen fibers which can affect the material properties of these tissues.

Left ventricular perimysial collagen fibers uncoil rather than stretch during diastolic filling.

The collagen fibers in the myocardium are initially wavy, suggesting that they may not be directly stretched for a portion of diastolic filling. To test whether the fibers gradually straighten and at what left ventricular (LV) pressure they become straight, 24 isolated, arrested rat hearts were fixed at physiologic diastolic LV pressures and changes in collagen structure were examined. As LV pressure increased, mean ( +/- SE) sarcomere length increased (1.80 +/- 0.02 to 1.88 +/- 0.02 from 0 mmHg to 26.3 +/- 4.1 mmHg) while the tortuosity of the perimysial fibers (fiber length/midline length) decreased (1.088 +/- 0.014 to 1.031 +/- 0.006 from 0 mmHg to 26.3 +/- 4.1 mmHg). Transmural variations in collagen structure paralleled the trends in sarcomere length (epicardial regions had longer sarcomeres and straighter collagen fibers than endocardial regions). These results indicate that there is a tight coupling between perimysial collagen fibers and myocytes, consistent with the nonlinear pressure-volume and pressure-sarcomere length relationships.

Enhanced regional deformation at the anterior papillary muscle insertion site after chordal transsection.

BACKGROUND: Clinical and experimental studies of mitral valve replacement have shown a depression of ventricular function after chordal transsection; most recent studies have proposed that this is secondary to a depression of local function near the papillary muscle insertion site. However, there is no direct experimental evidence for changes in local fiber shortening in the wall of the left ventricle overlying the papillary muscle. Accordingly, we investigated the effect of chordal transsection on left ventricular shape and on three-dimensional regional deformation of the myocardium near the insertion of the anterior papillary muscle. METHODS AND RESULTS: In six open-chest dogs, two sets of three transmural columns of radiopaque markers were implanted in the anterior wall, one set at the tip of the papillary muscle (basal) and one at the site of papillary muscle fiber insertion (apical). A Björk-Shiley mitral valve was placed in the left atrium adjacent to the native valve. Markers were then tracked with biplane cineradiography, and deformation was quantified with the use of finite strain analysis. Chordal transection resulted in reduced left ventricular end-systolic pressure and slowed relaxation. After chordal transsection, outward displacement of the ventricular wall and transverse shearing deformation were observed in the area of the papillary muscle during isovolumic contraction. Circumferential and radial strains during ejection were maintained at our basal site and enhanced on our apical site. CONCLUSIONS: Chordal transsection led to enhanced local shortening and wall thickening and regional strain nonuniformity. These results indicate that chordal transsection induces an unloading of myocardium at the papillary muscle insertion site and that the resulting heterogeneity of regional function is the mechanism for the reduced global function and slowed ventricular relaxation.

Transverse shear along myocardial cleavage planes provides a mechanism for normal systolic wall thickening.

Recent studies in humans and other species show that there is substantial transverse shear strain in the left ventricular myocardium, and others have shown transverse myocardial laminae separated by cleavage planes. We proposed that cellular rearrangement based on shearing along myocardial cleavage planes could account for > 50% of normal systolic wall thickening, since < 50% can be explained by increases in myocyte diameter. To test this hypothesis, we measured strains at two sites with different cleavage-plane anatomy in eight open-chest dogs. Columns of radiopaque markers were implanted in the left ventricular anterior free wall and septum. Markers were tracked with biplane cineradiography, and strains were quantified by using finite deformation techniques. Hearts were perfusion-fixed with glutaraldehyde, and cleavage-plane orientations at the bead sites were measured in three orthogonal planes. At subendocardial sites of the anterior left ventricular wall, where the cleavage planes approach the endocardium obliquely from the apical side of the surface normal in the longitudinal-radial plane (-67 +/- 11 degrees), systolic longitudinal-radial transverse shear (E23) was positive (0.14 +/- 0.08). At the septal sites where the subendocardial cleavage planes approach the endocardium obliquely from above the surface normal (44 +/- 12 degrees), E23 was negative (-0.12 +/- 0.08). The differences in cleavage-plane angle and E23 at the two sites were each highly significant (P < .0005). At both sites, the transverse shear strain accompanied substantial systolic wall thickening at the subendocardium (anterior, E33 = 0.44 +/- 0.16; septum, E33 = 0.22 +/- 0.14). These data are not representative of the behavior in midwall and outer wall sites, where cleavage-plane orientation was not consistently different between anterior left ventricle and septum. Our data indicate that rearrangement of myocytes by slippage along myocardial cleavage planes is in the correct direction and of sufficient magnitude in the subendocardium (inner third) to account for a substantial proportion (> 50%) of systolic wall thickening. Furthermore, three-dimensional reconstruction of the myocardial laminae and local comparison with maximum strain vectors indicate that for the inner third of the ventricular wall the maximum shear deformation is a result of relative sliding between myocardial laminae.

Depressed regional deformation near anterior papillary muscle.

The role of the papillary muscle in left ventricular function has received new attention. We hypothesized that regional mechanics of the left ventricular wall near the anterior papillary muscle are influenced by the papillary muscle insertion. We therefore studied three-dimensional regional mechanics in and near the anterior papillary muscle in anesthetized, open-chest dogs, using implanted radiopaque markers and biplane cineradiography. In seven dogs, deformation differed little between an anterior papillary muscle insertion site (PMA) and a more basal site (PMB) overlying the anterior papillary muscle. However, local shortening and wall thickening were depressed in both locations relative to anterior free wall sites (FWA, FWB) studied in five additional dogs. A distinct structural border was observed at the junction between the myocardial wall and anterior papillary muscle, which may preclude the use of homogeneous strain in that region. Data from within the anterior papillary muscle indicated that uniaxial measurements in the papillary muscle are extremely sensitive to the orientation of the measurement axis, possibly explaining the variety of papillary muscle shortening patterns reported by previous investigators.

Impaired subendocardial function in tachycardia-induced cardiac failure.

Chronic rapid ventricular pacing (CRVP) in many experimental models induces ventricular dilatation, reduced ejection fraction, and symptomatic congestive heart failure. We have investigated transmural mechanical function in the left ventricular (LV) wall of five Hanford miniature swine before and after CRVP-induced failure. Three columns of radiopaque markers 1 mm in diameter were implanted in the anterior LV wall through a median sternotomy. A pair of LV pacing wires were sutured into the myocardium, a pneumatic cuff was placed around the inferior vena cava (IVC), and two fluid-filled Silastic catheters were implanted into the LV apex. Two weeks after surgery, the pigs were suspended awake in a sling, and markers were tracked with biplane cineradiography. The hearts were paced for 3 wk (225-240 beats/min), and the study was repeated with the pacemaker off. Saline infusion and IVC occlusion were used to vary LV end-diastolic pressure (EDP) so control-to-failure comparisons could be made at matched LV EDPs. End-systolic strains in the circumferential (E11), longitudinal (E22), and transmural (E33) directions were quantified using finite element methods. There was a significant reduction in E11 and E33 for the subendocardium: in E11, from -0.27 to -0.18; in E33, from 0.83 to 0.46. There were no significant changes in subendocardial E22 or in any of the outer wall normal strains. These results indicate that CRVP causes substantial reduction of subendocardial, but not subepicardial, function; taken together with previous data indicating subendocardial hypoperfusion, these results support the contention that an imbalance between blood flow and oxygen demand plays a role in the etiology of heart failure in this model.

Effects of pressure overload on the passive mechanics of the rat left ventricle.

Both myocyte growth and changes in the extracellular matrix may affect the passive mechanics of the left ventricle (LV). Pressure-volume (PV) relationships and midwall two-dimensional strains versus passive loading were measured in isolated rat hearts 2 and 6 weeks after ascending aortic banding. Collagen area fractions and perimysial fibril orientations were determined with picrosirius-polarization microscopy, and the equatorial region of the LV was modeled with finite element analysis of a transversely isotropic cylinder with the same material properties in hypertrophy and control. Compared with weight-matched shams, heart weight increased at 2 (19%) and 6 (22%) weeks, as did LV wall thickness (6% and 31%, respectively). The PV curve became less compliant with hypertrophy; only circumferential strain decreased after hypertrophy. Collagen area fractions were not different at either subendocardium or subepicardium (3.37 +/- 1.06 versus 3.96 +/- 0.76 at 2 weeks and 3.61 +/- 1.30 versus 4.22 +/- 1.50 at 6 weeks for banded and sham, respectively; subendocardium). Collagen and muscle fiber orientations also did not change with hypertrophy. The finite element model predicted trends in the strains similar to those found experimentally. Thus, in this model of pressure-overload hypertrophy, the decreases in compliance and circumferential strain of the passive LV are not due to changes in the percentage of extracellular matrix, but rather to global geometric changes.

Effect of coronary artery reperfusion on transmural myocardial remodeling in dogs.

BACKGROUND: The effects of reperfusion after coronary occlusion on transmural remodeling of the ischemic region early and late after nontransmural infarction must importantly affect the recovery of regional function. Accordingly, analysis of local volume and three-dimensional strain was performed using a finite element method to determine regional remodeling. Systolic and remodeling strains were measured using radiographic imaging of three columns (approximately 1 cm apart) of four to six gold beads implanted across the left ventricular posterior wall in 6 dogs. METHODS AND RESULTS: After a control study, infarction was produced by 2 to 4 hours of proximal left circumflex coronary artery occlusion followed by reperfusion. Follow-up studies were performed at 2 days, 3 weeks, and 12 weeks with the dogs under anesthesia and in closed-chest conditions. Biplane cineradiography was performed to obtain the three-dimensional coordinates of the beads. At 2 days, end-systolic strains were akinetic with loss of normal transmural gradients of shortening and thickening. Remodeling strains (RS) were determined by use of a nonhomogeneous finite element method by referring the end-diastolic configuration during follow-up studies to its control state at matched end-diastolic pressures and heart rates. Tissue volume at 2 days increased substantially, more at the endocardium (30 +/- 7%) than at the epicardium (5 +/- 12%, P < .01); the increase was associated with an average RS in the wall-thickening direction of 0.18 +/- 0.15 (P < .01) with all other RS near zero. At 12 weeks systolic function partially recovered, with normal wall thickening in the epicardium (radial strain, 0.081 +/- 0.056 [control] versus 0.113 +/- 0.088 [12 weeks]) but with dysfunction in the endocardium (0.245 +/- 0.108 [control] versus 0.111 +/- 0.074 [P < .01] [12 weeks]). This inability of the inner wall to recover function may be related to increased transmural torsional shear and negative longitudinal-radial transverse shear in the inner wall. Volume loss occurred at 12 weeks in the endocardium (-36 +/- 16%) corresponding to transmural gradients in longitudinal RS and both transverse shear RS. Negative longitudinal RS was greater at the endocardium (-0.20 +/- 0.10) than at the epicardium (-0.06 +/- 0.05, P < .01). CONCLUSIONS: These results indicate the presence of marked subendocardial edema 2 days after reperfusion following 2 to 4 hours of coronary occlusion. At 3 months after reperfusion, however, there was volume loss in the inner wall due to shrinkage along the myofiber direction with reduced transmural function and loss of longitudinal shortening, while both tissue volume and function recovered completely in the outer wall.

Gradients of epicardial strain across the perfusion boundary during acute myocardial ischemia.

To study the mechanical interaction between acutely ischemic and adjacent perfused myocardium, nonhomogeneous distributions of end-systolic epicardial strain were measured using an array of radiopaque beads sewn on the left ventricular free wall of the pig during complete left circumflex coronary artery occlusion. The midwall perfusion boundary, demarcated by postmortem dye injection, was reconstructed over the span of the epicardial array. During ischemia, circumferential and longitudinal shortening remained significantly depressed up to 13 mm outside the ischemic region near the base of the ventricle, up to 8-9 mm at the midventricle, but only 0-1 mm near the apex (P < 0.05). Gradients of circumferential and longitudinal strain across the boundary were significantly different during both baseline conditions and acute ischemia (P = 0.0001). However, gradients of the change in the strain from baseline to ischemia were not different for the two components. These results support the concept that direction-dependent differences in the strain gradients across the boundary during ischemia were due to the preservation of the baseline regional variations of strain combined with a loss of systolic function in the ischemic region.

Scar remodeling and transmural deformation after infarction in the pig.

BACKGROUND: Changes in stress and tissue material properties have been proposed as important mechanical factors that may influence infarct expansion and subsequent healing. Because such changes will be reflected by alterations in the finite deformation of the tissue, we examined the direction and magnitude of myocardial deformation after coronary ligation in the pig. METHODS AND RESULTS: Gold beads were implanted in the left ventricular free wall of five pigs. After ligation of the coronary supply to the region containing the markers, we used biplane cineradiography to reconstruct the three-dimensional deformations of the myocardium during single cardiac cycles as well as the remodeling deformations that occurred over time. Deformations were studied at 1 and 3 weeks after infarction. The analysis of single cardiac cycles revealed permanent loss of systolic shortening immediately after ligation. However, significant passive systolic wall thickening (P < .001) and large shears were observed at 3 weeks in regions composed almost entirely of collagen. The analysis of remodeling deformations at 1 week revealed infarct expansion with a predominant axis that varied widely. At 3 weeks, a 30% to 60% reduction in local tissue volume was measured in the infarct region, with the principal direction of scar shrinkage nearly circumferential in all animals (range, -2 degrees to 35 degrees). CONCLUSIONS: We conclude that infarct expansion and scar shrinkage may be controlled by different factors. In addition, we conclude that measurement of systolic wall thickening alone is not always adequate to assess postinfarction regional contractile function.

Contribution of collagen matrix to passive left ventricular mechanics in isolated rat hearts.

Although it makes up only 2-6% of left ventricular dry weight, collagen is thought to be the major structural protein determining passive ventricular stiffness. However, the relationship between structure of the extracellular matrix and passive mechanics is not understood. Hence, to deplete the collagen matrix, 16 rat hearts were perfused with bacterial collagenase for 60 min. Quantitative morphology using picrosirius red revealed a 36% decrease in collagen area fraction predominantly in the medium-sized fibers. Scanning electron microscopy revealed damage to the endomysial struts. Passive pressure-volume curves showed increases in left ventricular volume at all pressures (from 0.203 +/- 0.061 to 0.265 +/- 0.061 ml at 5 mmHg, P < 0.0001). Strain during loading, calculated from lengths obtained from a triplet of piezoelectric crystals, was unchanged with collagen depletion. However, remodeling strain computed from the collagenase-treated state referred to the Krebs solution-treated state at the same ventricular pressure showed both circumferential (0.145 +/- 0.166 to 0.170 +/- 0.158) and longitudinal (0.070 +/- 0.120 to 0.068 +/- 0.069) stretching. Sarcomere lengths increased at all depths (5.2% at midwall). Thus alterations in the extracellular matrix lead to increased ventricular volume and sarcomere lengths without altering ventricular compliance.