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Biomedical subjects

Neil B Ingels

Publications and source records attributed to Neil B Ingels.

At least 19 recordsLinked to original sources
PubMed2007

Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.

OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. RESULTS: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.

Animals↗
PubMed2007

Altered myocardial shear strains are associated with chronic ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation (IMR) limits life expectancy and can lead to postinfarction global left ventricular (LV) dilatation and remodeling, the pathogenesis of which is not completely known. We tested the hypothesis that IMR perturbs adjacent myocardial LV systolic strains. METHODS: Thirteen sheep had three columns of miniature beads inserted across the lateral LV wall, with additional epicardial markers silhouetting the ventricle. One week later posterolateral infarction was created. Seven weeks thereafter, the animals were divided into two groups according to severity of IMR (< or = 1+, n = 7, IMR[-] vs > or = 2+, n = 6, IMR[+]). Four dimensional marker coordinates and quantitative histology were used to calculate ventricular volumes, transmural myocardial systolic strains, and systolic fiber shortening. RESULTS: Seven weeks after infarction, end-diastolic (ED) volume increased similarly in both groups, end-systolic (ES) E13 (circumferential-radial) shear increased in both groups, but more so in IMR(+) than IMR(-) (+0.12 vs 0.04, p < 0.005), and E12 (circumferential-longitudinal) shear increased in IMR(-) but not IMR(+) (+0.04 vs -0.01, p < 0.005). There were no significant differences in ED or ES remodeling strains or systolic fiber shortening between IMR(-) and IMR(+). CONCLUSIONS: An equivalent increase in LV end-diastolic (ED) volume in both groups, coupled with unchanged ED and end-systolic remodeling strains as well as systolic circumferential, longitudinal, and radial strains, argue against a global LV or regional myocardial geometric basis for the cardiomyopathy associated with IMR. Further, similar systolic fiber shortening in both groups militates against an intracellular (cardiomyocyte) mechanism. The differences in subepicardial E12 and E13 shears, however, suggest a causal role of altered interfiber (cytoskeleton and extracellular-matrix) interactions.

Animals↗
PubMed2006

Mitral leaflet remodeling in dilated cardiomyopathy.

BACKGROUND: Normal mammalian mitral leaflets have regional heterogeneity of biochemical composition, collagen fiber orientation, and geometric deformation. How leaflet shape and regional geometry are affected in dilated cardiomyopathy is unknown. METHODS AND RESULTS: Nine sheep had 8 radio-opaque markers affixed to the mitral annulus (MA), 4 markers sewn on the central meridian of the anterior mitral leaflet (AML) forming 4 distinct segments S1 to S4 and 2 on the posterior leaflet (PML) forming 2 distinct segments S5 and S6. Biplane videofluoroscopy and echocardiography were performed before and after rapid pacing (180 to 230 bpm for 15+/-6 days) sufficient to develop tachycardia-induced cardiomyopathy (TIC) and functional mitral regurgitation (FMR). Leaflet tethering was defined as change of displacement of AML and PML edge markers from the MA plane from baseline values while leaflet length was obtained by summing the segments between respective leaflet markers. With TIC, total AML and PML length increased significantly (2.11+/-0.16 versus 2.43+/-0.23 cm and 1.14+/-0.27 versus 1.33+/-0.25 cm before and after pacing for AML and PML, respectively; P<0.05 for both), but only segments near the edge of each leaflet (S4 lengthened by 23+/-17% and S5 by 24+/-18%; P<0.05 for both) had significant regional remodeling. AML shape did not change and no leaflet tethering was observed. CONCLUSIONS: TIC was not associated with leaflet tethering or shape change, but both anterior and posterior leaflets lengthened because of significant remodeling localized near the leaflet edge. Leaflet remodeling accompanies mitral regurgitation in cardiomyopathy and casts doubt on FMR being purely "functional" in etiology.

Animals↗
PubMed2006

Effects of undersized mitral annuloplasty on regional transmural left ventricular wall strains and wall thickening mechanisms.

BACKGROUND: Undersized mitral annuloplasty, widely used for ischemic and functional mitral regurgitation (MR), has been proposed as an "annular solution to a ventricular problem." Beyond relief of MR, it is thought to improve global left ventricular (LV) shape, hence potentially reducing myocardial stress and promoting beneficial reverse LV remodeling. We previously observed that undersized annuloplasty inhibited systolic wall thickening at the LV base near the mitral annulus. In this study, we measured the effects of undersized annuloplasty on regional transmural LV wall fiber and sheet strains and wall thickening mechanisms. METHODS AND RESULTS: Nine sheep had transmural radiopaque beadsets surgically inserted into anterobasal and lateral equatorial LV regions, with additional markers silhouetting the LV and mitral annulus. 4-Dimensional marker dynamics were studied with biplane videofluoroscopy before and after tightening an adjustable Paneth-type mitral annuloplasty suture. Transmural circumferential, longitudinal, and radial systolic and remodeling strains in the subepicardium (20% depth), midwall (50%), and subendocardium (80%) in both regions were computed. Fiber and sheet angles from quantitative regional histology allowed transformation of these strains into local fiber (f), sheet (s), and sheet-normal (n) coordinates. Further analysis calculated the transmural contributions of sheet extension (E(ssc)), sheet thickening (E(nnc)), and sheet shear (E(snc)) to systolic wall thickening (E(33)). In the anterobasal region, undersized annuloplasty reduced systolic wall thickening (E33) by &50% at all transmural depths by inhibiting: (1) subendocardial systolic fiber shortening (-0.10+/-0.05 versus -0.04+/-0.05; P<0.05); (2) subepicardial (0.16+/-0.15 versus 0.09+/-0.08; P<0.05) and subendocardial (0.45+/-0.40 versus 0.19+/-0.18; P<0.05) systolic sheet thickening; (3) midwall sheet extension (0.22+/-0.12 versus 0.11+/-0.06; P<0.05); and (4) transmural sheet shear (subepicardium, -0.14+/-0.07 versus -0.08+/-0.07; midwall, 0.21+/-0.12 versus 0.10+/-0.11; subendocardium, -0.19+/-0.23 versus -0.11+/-0.16; P<0.05). In the remote lateral equatorial region, fiber-sheet strains and E33 were unchanged. CONCLUSIONS: In this acute animal study, undersized annuloplasty inhibited systolic wall thickening in the anterobasal region by reducing subendocardial systolic fiber shortening and laminar sheet wall thickening, but had no effects in a more distant LV region. This suggests that undersized mitral annuloplasty may have potentially deleterious effects on local myocardial mechanics.

Animals↗
PubMed2006

Passive ventricular constraint prevents transmural shear strain progression in left ventricle remodeling.

BACKGROUND: Passive ventricular constraint provides external cardiac support to reduce left ventricular (LV) wall stress and myocardial stretch, which are primary determinants of LV remodeling. Altered wall strain results in cytokine and reactive oxygen species production, which, in turn, stimulates apoptosis and extracellular matrix disruption and could be an important trigger for adverse global LV dilatation and remodeling. The effects of the Acorn cardiac support device (CSD) on regional transmural LV wall strains, however, remain unknown. METHODS AND RESULTS: Thirty-three sheep had transmural radiopaque beadsets surgically inserted into the anterior basal and lateral equatorial LV walls, with additional markers silhouetting the left ventricle. Eight animals had CSD implanted (myocardial infarction [MI]+CSD). One week thereafter, the MI+CSD group and 10 animals without CSD (MI) underwent posterior LV infarction by snaring obtuse marginal coronary arteries. Fifteen animals (Sham) had no infarction or CSD. 4D marker dynamics were measured with biplane videofluoroscopy 1 and 8 weeks postoperatively. LV volumes, sphericity index, and transmural circumferential, longitudinal, and radial systolic strains were analyzed. Compared with Sham, infarction (MI) dilated the heart, reduced sphericity index (LV length/width), and increased longitudinal-radial shear strains in the inner half of both the anterior and lateral LV walls. CSD prevented this shear strain perturbation, minimized LV end diastolic volume increase, and augmented the LV sphericity index. CONCLUSIONS: Prophylactic CSD prevented infarct-induced shear strain progression not only in myocardium adjacent to, but also remote from, the infarct. CSD also prevented LV dilatation and sphericalization. By attenuating shear strain abnormalities, CSD could prevent the heart from entering into a positive feedback loop of further LV dilatation and exaggeration of LV wall stress and may reduce biochemical triggers portending adverse LV remodeling.

Animals↗
PubMed2006

Posterior mitral leaflet extension: an adjunctive repair option for ischemic mitral regurgitation?

BACKGROUND: Residual or recurrent mitral regurgitation frequently occurs after mitral valve repair for ischemic mitral regurgitation with an annuloplasty ring. Because annuloplasty primarily addresses annular dilatation, we studied an adjunctive technique that might correct restricted leaflet (Carpentier type IIIb) systolic closing motion, which often accompanies annular dilatation in patients with ischemic mitral regurgitation. METHODS: Six sheep had radiopaque markers placed on the left ventricle, mitral leaflets and annulus, and mitral subvalvular apparatus. A pericardial patch was sutured into the middle scallop of the posterior mitral valve leaflet and furled in with a reefing stitch placed in the radial axis. Posterolateral left ventricular myocardial ischemia was created by using proximal circumflex occlusion to induce acute ischemic mitral regurgitation. Under open-chest conditions, 3-dimensional marker coordinates were measured by using biplane videofluoroscopy at baseline and during acute ischemia both before and after release of the reefing stitch (leaflet extension); transesophageal echocardiography was used to grade ischemic mitral regurgitation. RESULTS: Leaflet apical systolic tethering was not improved by leaflet extension, but ischemic mitral regurgitation decreased (control, 0.9 +/- 0.3*; ischemia, 2.4 +/- 0.3; leaflet extension, 1.5 +/- 0.3; *P < 0.002). Posterior mitral valve leaflet midline length (control, 1.45 +/- 0.09*; ischemia, 1.53 +/- 0.10; leaflet extension, 1.83 +/- 0.13*; *P < 0.001) and posterior mitral valve leaflet middle scallop area (control, 1.66 +/- 0.20 cm2*; ischemia, 1.91 +/- 0.22 cm2; leaflet extension, 2.36 +/- 0.22 cm2*; *P < 0.006) increased with leaflet extension because of patch unfurling (mean +/- 1 standard error of the mean; repeated-measures analysis of variance, Dunnet post-hoc test vs ischemia). CONCLUSIONS: Posterior mitral valve leaflet extension ameliorated acute ischemic mitral regurgitation but did not correct the abnormal apically restricted systolic posterior mitral valve leaflet closing motion. This technique might be a useful adjunct repair in combination with ring annuloplasty for ischemic mitral regurgitation, but the clinical role of this adjunct remains to be defined in patients.

Animals↗
PubMed2006

Transmural left ventricular shear strain alterations adjacent to and remote from infarcted myocardium.

BACKGROUND AND AIM OF THE STUDY: In some patients, dysfunction in a localized infarct region spreads throughout the left ventricle to aggravate mitral regurgitation and produce deleterious global left ventricular (LV) remodeling. Alterations in transmural strains could be a trigger for this process, as these changes can produce apoptosis and extracellular matrix disruption. The hypothesis was tested that localized infarction perturbs transmural strain patterns not only in adjacent regions but also at remote sites. METHODS: Transmural radiopaque beadsets were inserted surgically into the anterior basal and lateral equatorial LV walls of 25 sheep; additional markers were used to silhouette the left ventricle. One week thereafter, 10 sheep had posterior wall infarction from (obtuse marginal occlusion, INFARCT) and 15 had no infarction (SHAM). Four-dimensional marker dynamics were studied with biplane videofluoroscopy eight weeks later. Fractional area shrinkage, LV volumes and transmural circumferential, longitudinal and radial systolic strains were analyzed. RESULTS: Compared to SHAM, INFARCT greatly increased longitudinal-radial shear (mid-wall: 0.07 +/- 0.07 versus 0.14 +/- 0.06; subendocardium: 0.03 +/- 0.07 versus 0.20 +/- 0.08) in the inner half of the lateral LV wall and increased circumferential-radial shear (mid-wall: 0.03 +/- 0.05 versus 0.10 +/- 0.04; subepicardium: 0.02 +/- 0.05 versus 0.12 +/- 0.10) increased in the outer half of the LATERAL wall. In the ANTERIOR wall, INFARCT also increased longitudinal-radial shear (midwall: 0.01 +/- 0.05 versus 0.12 +/- 0.04; subendocardium: 0.04 +/- 0.09 versus 0.25 +/- 0.20) in the inner layers. CONCLUSION: Increased transmural shear strains were found not only in an adjacent region, but also at a site remote from a localized infarction. This perturbation could trigger remodeling processes that promote the progression of ischemic cardiomyopathy. A better understanding of this process is important for the future development of surgical therapies to reverse destructive LV remodeling.

Animals↗
PubMed2006

Left ventricular volume shifts and aortic root expansion during isovolumic contraction.

BACKGROUND AND AIM OF THE STUDY: Aortic valve opening involves conformational changes of the aortic root, including the ventricular-aortic junction (VAJ), sinotubular junction (STJ), and cusps. Moreover, the aortic root is contiguous with the left ventricular outflow tract (LVOT), which changes diameter throughout the cardiac cycle. Aortic root expansion prior to valve opening facilitates outward displacement of aortic cusp attachments, which helps flatten the cusps, thereby reducing cusp stress and fatigue, ultimately enhancing functional valve durability. The mechanisms underlying aortic root expansion prior to valve opening, however, remain incompletely characterized. The study aim was to establish a link between such aortic root expansion and intraventricular volume shifts into the LVOT during isovolumic contraction (IVC). METHODS: Miniature radiopaque markers were implanted on the left ventricle, VAJ, STJ, and aortic cusps of six sheep. After one week, 3-D marker coordinates were obtained using biplane videofluoroscopy (60 Hz). Triangular areas at the VAJ and STJ were calculated; LV main chamber (non-LVOT) and LVOT volumes were calculated using multiple tetrahedra. End-diastole was defined as the peak of the electrocardiogram R-wave, and end-IVC when aortic cusp separation began. RESULTS: During IVC, blood within the left ventricle was redistributed to the LVOT: mean LVOT volume was increased (+0.2 +/- 0.1 ml, p = 0.009) as non-LVOT volume fell (-0.8 +/- 0.4 ml, p = 0.006). Concomitantly, the aortic root expanded as both VAJ and STJ areas increased (+0.23 +/- 0.12 cm2 (p = 0.005) and +0.25 +/- 0.14 cm2 (p = 0.007), respectively) prior to aortic cusp separation. CONCLUSION: Aortic root expansion prior to valve opening is closely related to intraventricular volume shifts into the LVOT during IVC. Such volume shifts may 'prime' the aortic valve for ejection. These findings expand our understanding of cardiac dynamics by showing that blood acts as a coupling link between various cardiac units. Preservation of these normal aortic root dynamics may enhance the efficacy and durability of aortic surgical interventions.

Animals↗
PubMed2005

Subvalvular repair: the key to repairing ischemic mitral regurgitation?

BACKGROUND: Residual or recurrent mitral regurgitation frequently occurs after mitral ring annuloplasty repair for ischemic mitral regurgitation (IMR), because annuloplasty primarily addresses annular dilatation. We describe a subvalvular repair technique addressing posterior papillary muscle (PPM) displacement. METHODS AND RESULTS: Ten sheep had radiopaque markers placed on the left ventricle (LV) and mitral apparatus. A suture was anchored at the right fibrous trigone, passed through the PPM tip and LV wall, and exteriorized through a tourniquet (STRING-1). A second suture was anchored transmurally in the high septum (anterobasal LV wall) and passed through the PPM and LV wall (STRING-2). Reversible posterolateral ischemia was induced by temporarily occluding the proximal circumflex artery. Under open chest conditions, 3D marker coordinates were obtained with biplane videofluoroscopy at baseline and during acute ischemia before and after tightening of each STRING using transesophageal echocardiography to grade IMR. IMR decreased (mean+/-SEM, 2.0+/-0.1 to 1.2+/-0.1; P<0.05) when STRING-1 was tightened, did not change after tightening STRING-2 (2.3+/-0.1 to 2.3+/-0.1), and decreased after tightening both sutures (STRING-1+2, 2.3+/-0.2 to 1.3+/-0.2; P<0.05). STRING-1 and STRING-1+2 (STRING-1, 1.7+/-0.4 mm; STRING-2, 0.7+/-0.5 mm; STRING-1+2, 1.5+/-0.3 mm; P<0.05) resulted in significant PPM basal repositioning. Tightening of any STRING sutures did not affect anterior mitral leaflet excursion. CONCLUSIONS: Basal repositioning of the PPM with STRING-1 reduced acute IMR without concomitant annular reduction. This technique may be a useful adjunct if residual IMR is likely after undersized ring annuloplasty.

Acute Disease↗
PubMed2005

Annular height-to-commissural width ratio of annulolasty rings in vivo.

BACKGROUND: A "saddle-shaped" mitral annulus with an optimal ratio between annular height and commissural diameter may reduce leaflet and chordal stress and is purported to be conserved across mammalian species. Whether annuloplasty rings maintain this relationship is unknown. METHODS AND RESULTS: Twenty-three adult sheep underwent implantation of radiopaque markers on the left ventricle and mitral annulus. Eight animals underwent implantation of a Carpentier-Edwards Physio ring, 7 underwent a Medtronic Duran flexible ring, and 8 served as controls. Animals were studied with biplane videofluoroscopy 7 to 10 days postoperatively. Annular height and commissural width (CW) were determined from 3D marker coordinates, and annular height:CW ratio (AHWCR) was calculated. Annular height was similar in Control and Duran animals but significantly lower in the Physio group at end diastole (8.4+/-3.8, 6.7+/-2.3, and 3.4+/-0.6 mm, respectively, for Control, Duran, and Physio; ANOVA=0.005) and at end systole (14.5+/-6.2, 10.5+/-5.5, and 5.8+/-2.5 mm, respectively, for Control, Duran, and Physio; ANOVA=0.004). Both ring groups reduced CW significantly relative to Control. AHCWR did not differ between Control and Duran but was lower in Physio (23+/-11%, 24+/-7%, and 12+/-2% at end diastole and 42+/-17%, 37+/-17%, and 21+/-10% at end systole, respectively, for Control, Duran, and Physio, respectively; ANOVA <0.05 for both). CONCLUSIONS: Mitral annular height and AHWCR of the native valve were unchanged by a Duran ring, whereas the Physio ring led to a lower AHWCR. Theoretically, such a flexible annuloplasty ring may provide better leaflet stress distribution by maintaining normal AHWCR.

Animals↗
PubMed2005

Transmural sheet strains in the lateral wall of the ovine left ventricle.

In an attempt to provide a better understanding of our finding that regions with contracting left ventricular myofibers need not develop a significant transmural systolic wall thickening gradient, the analytic approach of Costa et al. was applied to the four-dimensional dynamic data obtained 1 and 8 wk after surgical implantation of transmural radiopaque beads in the lateral equatorial left ventricular wall in seven ovine hearts. Quantitative histology of tissue blocks demonstrated that fiber angles varied linearly across the wall in this region from -37 degrees in the subepicardium to +18 degrees in the subendocardium. Sheet angles exhibited a pleated-sheet behavior, alternating sign from subepicardium to subendocardium. From end diastole (reference configuration) to end systole (deformed configuration), fiber strain was uniformly negative, sheet extension and sheet thickening were uniformly positive, and sheet-normal shear contributed to wall thickening at all wall depths. Subepicardial radial wall thickening increased significantly from week 1 to week 8, with significant increases in the contributions from subepicardial sheet extension and sheet-normal shear. At 1 and 8 wk, the contribution of sheet-normal shear to wall thickening was substantial at all transmural depths; the contribution of sheet extension to wall thickening was greatest in the subepicardium and least in the subendocardium, and the contribution of sheet thickening to wall thickening was greatest in the subendocardium and least in the subepicardium. A mechanistic model is proposed that provides a working hypothesis that a selective decrease in subepicardial intercellular matrix stiffness is responsible for elimination of the transmural wall thickening gradient 1-8 wk after marker implantation surgery.

Adaptation, Physiological↗
PubMed2005

Alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion.

OBJECTIVE: Helically oriented left ventricular fibers assemble into transmural sheets, which are important for wall-thickening mechanics: 15% fiber shortening results in 40% cross-fiber left ventricular wall thickening and a 60% ejection fraction through sheet extension, thickening, and shear. Normal cardiac microstructure and strains are optimized; deviations could result in apoptosis and deleterious matrix remodeling, which degenerates into global cardiomyopathy. We studied alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion. METHODS: Nine sheep had radiopaque markers implanted to measure left ventricular systolic fractional area shortening; 3 transmural bead columns were inserted into the midlateral wall for strain analysis. Three-dimensional marker coordinates were obtained with biplane videofluoroscopy before and during 70 seconds of ischemia. Systolic strains were quantified along circumferential, longitudinal, and radial axes (n = 9) and were transformed into fiber-sheet coordinates by using quantitative microstructural measurements (n = 5). RESULTS: A functional border was defined in the midlateral left ventricle; ischemia decreased posterolateral fractional area shortening, and anterolateral fractional area shortening increased. In this demarcation junction, subepicardial end-systolic radial wall thickening decreased (0.16 +/- 0.08 vs 0.11 +/- 0.06) and sheet-normal shear was abolished (0.08 +/- 0.04 vs -0.01 +/- 0.03). Longitudinal shortening decreased in the subepicardium and midwall (-0.05 +/- 0.04 vs +/- -0.01 +/- 0.06), but circumferential-radial shear increased at these depths (0.04 +/- 0.04 vs 0.11 +/- 0.05). Subendocardial fiber stretch occurred during early systole (-0.01 +/- 0.03 vs 0.02 +/- 0.03), and end-systolic fiber-sheet shear increased (0.07 +/- 0.01 vs 0.11 +/- 0.04, all P < .05). CONCLUSIONS: Increased circumferential-radial shear and altered fiber-sheet strains reflect mechanical interactions between ischemic and nonischemic myocardium, which might be important in triggering remodeling processes that evolve into global ischemic cardiomyopathy.

Animals↗
PubMed2005

Annular or subvalvular approach to chronic ischemic mitral regurgitation?

OBJECTIVE: We sought to investigate whether annular or subvalvular interventions corrected chronic ischemic mitral regurgitation differently. METHODS: Sheep underwent placement of markers on the left ventricle, mitral annulus, papillary muscles (anterior and posterior), and both leaflet edges. A transannular suture (septal-lateral annular cinching) was anchored to the midseptal mitral annulus and externalized through the midlateral mitral annulus. Another suture (papillary muscle repositioning) from the posterior papillary muscle was passed through the mitral annulus near the posterior commissure and externalized. After 7 days, 3-dimensional marker data were obtained before inducing posterolateral myocardial infarction. After 7 weeks, animals in whom chronic ischemic mitral regurgitation developed (n = 10) were restudied before and after pulling septal-lateral annular cinching or papillary muscle repositioning sutures. End-systolic septal-lateral annular diameter and 3-dimensional displacement of the papillary muscles and leaflet edges were computed. RESULTS: Infarction increased mitral regurgitation (0.6 +/- 0.5 to 2.3 +/- 1.1); mitral annular septal-lateral dilation (4 +/- 1 mm); posterior papillary muscle displacement laterally (4 +/- 2 mm), posteriorly (9 +/- 3 mm), and toward the annulus (2 +/- 1 mm); posterior mitral leaflet apical tethering (3 +/- 1 mm); and interleaflet separation (+3 +/- 1 mm, P < .05 baseline vs chronic ischemic mitral regurgitation). Septal-lateral annular cinching reduced septal-lateral dimension (-9 +/- 3 mm), corrected lateral posterior papillary muscle displacement (4 +/- 1 mm) and septal-lateral interleaflet separation (-4 +/- 2 mm), and decreased mitral regurgitation (0.6 +/- 0.6, P < .05 septal-lateral annular cinching vs chronic ischemic mitral regurgitation) without affecting posterior leaflet restriction. Papillary muscle repositioning reduced septal-lateral diameter (-4 +/- 1 mm), moved the anterior papillary muscle closer to the annulus (2 +/- 1 mm), and relieved posterior leaflet apical restriction (2 +/- 1 mm, P < .05 papillary muscle repositioning vs chronic ischemic mitral regurgitation) but did not change lateral posterior papillary muscle displacement or decrease mitral regurgitation (1.9 +/- 1.2). CONCLUSIONS: Septal-lateral annular cinching moved the lateral annulus and the posterior papillary muscle closer to the septum and reduced mitral regurgitation unlike posterior papillary muscle repositioning, and thus the key mitral subvalvular repair component must correct posterior papillary muscle lateral displacement.

Animals↗
PubMed2005

Altered mitral valve kinematics with atrioventricular and ventricular pacing.

BACKGROUND AND AIM OF THE STUDY: Pacing-induced mitral regurgitation contributes to the 'pacemaker syndrome', which usually is observed with ventricular (V) pacing, but has also been reported with atrioventricular (AV) sequential pacing. Effects of different pacing modes on 3-D kinematics of the mitral apparatus are incompletely understood. METHODS: Radio-opaque markers were placed on the left ventricular (LV) and mitral apparatus including the annulus, leaflets and papillary muscles of eight sheep. Hemodynamic and 3-D dynamic marker geometry were obtained one week later with biplane videofluoroscopy (60 Hz) during atrial (pacing site = left atrium), AV-sequential (140 ms interval) and (anterolateral LV epicardial) ventricular pacing. RESULTS: Compared with A-pacing (*p <0.05): 1) The regurgitant fraction increased with both AV- and V-pacing (A: 6 +/- 3%, AV: 13 +/- 3%*, V: 15 +/- 2%*); 2) AV and V-pacing delayed closure at the leaflet center (A: 21 +/- 10 ms, AV: 52 + 5 ms*, V: 92 +/- 6 ms*) and posterior commissure (A: 17 +/- 10 ms, AV: 46 +/- 8 ms*, V: 94 +/- 6 ms*). V-pacing delayed valve closure at the anterior commissure (A: 27 +/- 9 ms, V: 94 +/- 6 ms*); 3) The end-diastolic leaflet opening angle was greater with AV- and V-pacing (anterior mitral leaflet (AML): A: 32 +/- 2 degrees, AV: 41 +/- 4 degrees*, V: 46 +/- 4 degrees*; posterior mitral leaflet (PML): A: 56 +/- 4 degrees, AV: 62 +/- 3 degrees*, V: 68 +/- 3 degrees*); 4) 'Effective' end-diastolic PML midline length was reduced with AV- and V-pacing (A: 11.2 +/- 0.7 mm, AV: 10.0 +/- 0.4 mm*, V: 10.2 +/- 0.3 mm*), as was the distance from each papillary muscle (PM) tip to the AML edge ('effective' chordal length) close to the commissures (anterior PM-AML: A: 31.5 +/-1.8 mm, AV: 30.5 +/- 1.9 mm*, V: 29.7 +/- 1.8 mm*; posterior PM-AML: A: 33.7 +/- 1.8 mm, AV: 33.1 +/- 1.9 mm*, V: 32.8 +/- 1.9 mm*). CONCLUSION: Both ventricular and AV-sequential-pacing resulted in a more widely opened valve at end-diastole and leaflet dyssynchrony with delayed mitral valve closure and early systolic mitral regurgitation. These alterations which result in pacing-induced mitral regurgitation may be clinically important in patients with impaired LV function.

Animals↗
PubMed2005

Effect of cutting second-order chordae on in-vivo anterior mitral leaflet compound curvature.

BACKGROUND AND AIM OF THE STUDY: Leaflet curvature determines leaflet stress. In order to assess the influence of second-order chordae (2 degrees CT) on anterior mitral valve leaflet (AMVL) geometry, AMVL curvature was measured before (Baseline) and after (CUT) cutting the 2 degrees CT. METHODS: Miniature radiopaque markers were sutured onto the AMVL in eight sheep: four along the central-meridian from mid-septal annulus to the free-margin; and one each at the 2 degrees CT insertion. Biplane videofluoroscopic data were acquired (open-chest) before and after CUT. Marker-triplet 3-D coordinates were used to calculate radii-of-curvature at LVPmax along the central-meridian (ROCm) and across the AMVL belly (commissure-commissure axis, ROCc-c). RESULTS: CUT did not change LVPmax (111 +/- 12 versus 106 +/- 11 mmHg; p = 0.19). At baseline, the AMVL central-meridian had compound curvature: Convex to the left ventricle near the annulus (-ROCm) and concave near the free-margin (+ROCm). After CUT, the AMVL flattened: ROCm increased near the annulus (from -1.37 +/- 0.52 to -12.58 +/- 29.04 cm; p = 0.02), but did not change near the edge. In the commissure-commissure axis, ROCc-c was concave to the left ventricle at baseline and increased after CUT in all eight animals. In five sheep, ROCc-c was increased (from 1.93 +/- 1.01 to 2.80 +/- 1.36 cm; p = 0.03), but in three sheep ROCc-c was increased and inverted (from 3.65 +/- 2.17 to -1.72 +/- 0.53 cm; p = 0.03), becoming convex to the left ventricle. CONCLUSION: Compound curvature along the AMVL central-meridian appears to be an intrinsic leaflet property that persists even without support from second-order chordae, whereas concave curvature in the commissure-commissure axis is more dependent on intact second-order chordae. Leaflet compound curvature must be incorporated into future finite element models to characterize leaflet stresses accurately. The importance of second-order chordae in maintaining leaflet shape must be considered during mitral repair. A larger ROC increases leaflet stresses, while reversal of ROC changes tensile stress to compressive stress; this might trigger deleterious leaflet remodeling after chordal cutting.

Animals↗
PubMed2004

Transmural cardiac strains in the lateral wall of the ovine left ventricle.

The constant-volume property of contracting cardiac muscle has been invoked in models of heart wall mechanics that predict that systolic subendocardial left ventricular (LV) wall thickening must significantly exceed subepicardial thickening. To examine this prediction, we implanted arrays of radiopaque markers to measure lateral equatorial wall transmural strains and global and regional LV geometry in seven sheep and studied the four-dimensional dynamics of these arrays using biplane videofluoroscopy (60 Hz) in anesthetized intact animals 1 and 8 wk after surgery. A transmural gradient of systolic lateral wall thickening was observed at 1 wk (P = 0.009; linear regression) but was no longer present at 8 wk (P = 0.243). Referenced to end diastole, group mean (+/-SD) end-systolic radial subepicardial, midwall, and subendocardial wall thickening strains were, respectively, 0.08 +/- 0.08, 0.14 +/- 0.08, and 0.22 +/- 0.12 at 1 wk and 0.19 +/- 0.07 (P = 0.02; 1 vs. 8 wk), 0.20 +/- 0.04, and 0.23 +/- 0.07 at 8 wk. With the exception of an 8-ml (7%) increase in end-diastolic volume (P = 0.04) from 1 to 8 wk, LV shape and hemodynamics were otherwise unchanged. We conclude that equivalent hemodynamics can be generated by the left ventricle with or without a transmural gradient of systolic wall thickening in this region; thus such a gradient is unlikely to be a fundamental property of the contracting LV myocardium. We discuss some implications of these findings regarding mechanisms involved in systolic wall thickening.

Animals↗
PubMed2004

Direct measurement of transmural laminar architecture in the anterolateral wall of the ovine left ventricle: new implications for wall thickening mechanics.

Laminar, or sheet, architecture of the left ventricle (LV) is a structural basis for normal systolic and diastolic LV dynamics, but transmural sheet orientations remain incompletely characterized. We directly measured the transmural distribution of sheet angles in the ovine anterolateral LV wall. Ten Dorsett-hybrid sheep hearts were perfusion fixed in situ with 5% buffered glutaraldehyde at end diastole and stored in 10% formalin. Transmural blocks of myocardial tissue were excised, with the edges cut parallel to local circumferential, longitudinal, and radial axes, and sliced into 1-mm-thick sections parallel to the epicardial tangent plane from epicardium to endocardium. Mean fiber directions were determined in each section from five measurements of fiber angles. Each section was then cut transverse to the fiber direction, and five sheet angles (beta) were measured and averaged. Mean fiber angles progressed nearly linearly from -41 degrees (SD 11) at the epicardium to +42 degrees (SD 16) at the endocardium. Two families of sheets were identified at approximately +45 degrees (beta(+)) and -45 degrees (beta(-)). In the lateral region (n = 5), near the epicardium, sheets belonged to the beta(+) family; in the midwall, to the beta(-) family; and near the endocardium, to the beta(+) family. This pattern was reversed in the basal anterior region (n = 4). Sheets were uniformly beta(-) over the anterior papillary muscle (n = 2). These direct measurements of sheet angles reveal, for the first time, alternating transmural families of predominant sheet angles. This may have important implications in understanding wall mechanics in the normal and the failing heart.

Animals↗