Biomedical subjects

Yoshiharu Enomoto

Publications and source records attributed to Yoshiharu Enomoto.

13 recordsLinked to original sources

PubMed2006

In-vivo dynamic deformation of the mitral valve anterior leaflet.

BACKGROUND: Surgical techniques have been developed for mitral valve repair for a wide range of pathologies. However, excessive tissue stress and damage have been identified as etiologic factors limiting long-term durability. Before computational models to optimize valve repair can be realistically developed, in-vivo dynamic mitral valve leaflet strain data are required. However, these data do not presently exist. In the present study, a sheep model and sonomicrometry were used to compute the in-surface Eulerian strain tensor of the anterior leaflet over the cardiac cycle at varying afterloads. METHODS: The anterior leaflet of nine Dorsett sheep (35 kg to 45 kg) was instrumented with nine 1-mm hemispherical piezoelectric transducers in a 15-mm square array. Three-dimensional crystal spatial positions were recorded at 250 Hz over several cardiac cycles, with peak left ventricular pressures varying from 90 mm Hg to 200 mm Hg. The in-surface Eulerian strain tensor was computed from the crystal displacements. RESULTS: The mitral valve anterior leaflet experiences large anisotropic strains and peak strain rates of 400%/s, followed by an absolute cessation of any deformation during systole. Increasing left ventricular pressure also increased the effective leaflet stiffness but not the peak strains. CONCLUSIONS: We report the first data on the dynamic in-vivo strain tensor of a functioning mitral valve anterior leaflet, which indicated large anisotropic strains and very high strain rates. Our observations also suggest that changes in left ventricular pressure and annular geometry result in altered effective leaflet stiffness, and may be an important factor in reducing leaflet stress and as such potentially affect mitral valve repair longevity.

Animals↗

PubMed2006

Effects of hemodynamic alterations on anterior mitral leaflet curvature during systole.

OBJECTIVES: The application of repair techniques to treat mitral valve incompetence has increased progressively during the past 20 years. Unfortunately, recent reports have demonstrated the longevity of these repairs to be less than previously believed. Most repair failures are stress related. Computational models to optimize valve repair are in development, but to be brought to fruition, a better understanding of dynamic leaflet geometry is necessary. In this study, sonomicrometry was used in an ovine model to compute systolic leaflet curvature at varying afterloads and states of contractility. METHODS: The anterior leaflet of 12 sheep was instrumented with 5 piezoelectric transducers in a cruciate array. Systolic blood pressure ranged from 90 to 200 mm Hg with increasing phenylephrine hydrochloride infusion. Epinephrine was used to vary contractile state. Leaflet curvature was calculated continuously (200 Hz) during systole. RESULTS: Anterior leaflet curvature in the septolateral direction was double that in the intercommisural direction. There were also significant changes in leaflet curvature during systole. Curvature in neither direction was affected by afterload. Epinephrine augmented intercommisural curvature in a dose-independent fashion, whereas it had no effect on curvature in the septolateral direction. CONCLUSIONS: Dynamic mitral anterior leaflet geometry was found to be amazingly constant over a wide range of hemodynamic conditions. These data provide information about leaflet geometry that will aid in the construction of realistic computational models. Such models may facilitate the design of annuloplasty rings and surgical techniques that minimize leaflet stress and increase mitral valve repair longevity.

Animals↗

PubMed2005

Early ventricular restraint after myocardial infarction: extent of the wrap determines the outcome of remodeling.

BACKGROUND: Early infarct expansion initiates adverse remodeling, leads to left ventricular dilatation and portends a poor long-term outcome. Early mechanical prevention of infarct expansion has been proposed as a method to improve remodeling, but the extent of ventricular restraint necessary to optimize the salutary effect is not known. We tested the hypothesis that left ventricular restraint (wrap) is superior to infarct stiffening (patch). METHODS: Infarction of 20% to 25% of the left ventricle was induced by coronary ligation in 69 sheep. Infarcts were either anteroapical (n = 33) or posterobasal (n = 36). Animals with each infarct received either no treatment (anteroapical, n = 26; posterobasal, n = 17), infarct stiffening with a localized Marlex mesh patch (posterobasal, n = 9) or left ventricular wrapping with Merseline mesh (anteroapical, n = 7; posterobasal, n = 10). End-systolic volume, end-diastolic volume, end-systolic muscle to cavity area ratio, left ventricular sphericity, ejection fraction, and degree of mitral regurgitation as determined by quantitative echocardiography were assessed before infarction and at 2, 5, and 8 weeks after infarction to evaluate the extent of left ventricular remodeling. RESULTS: Control animals in both groups experienced adverse remodeling. Anteroapical infarct animals developed large left ventricular aneurysms and the posterobasal infarct animals developed severe mitral regurgitation. Early infarct stiffening did not significantly improve any aspect of remodeling due to the posterobasal infarct. Early left ventricular wrapping significantly improved remodeling after both types of infarctions. CONCLUSIONS: Early left ventricular wrapping attenuates infarct expansion and has a salutary effect on remodeling. Simple infarct stiffening alone is not effective.

Animals↗

PubMed2005

Borderzone geometry after acute myocardial infarction: a three-dimensional contrast enhanced echocardiographic study.

BACKGROUND: Regional myocardial geometry, function, and perfusion status are critical variables for understanding infarction-induced left ventricle (LV) remodeling. Three-dimensional contrast echocardiography (3DCE) is uniquely suited to measure these parameters. We evaluate the ability of 3DCE to assess geometric changes in the normally perfused but hypocontractile borderzone myocardium (BZM) immediately after a myocardial infarction (MI) in an ovine model, and we compare 3DCE with two-dimensional contrast echocardiography (2DCE) in the long and short axis. METHODS: Four sheep were studied with 3DCE and 4 were studied using 2DCE, before and 30 minutes after an anteroapical MI. Each 3DCE data set was acquired over 18 consecutive cardiac cycles. The LV geometry was reconstructed and perfusion data spatially correlated, thereby constituting a 3D model of ventricular geometry and perfusion. The borderzone was defined as the contrast-perfused myocardium adjacent to the infarct. RESULTS: The 2DCE short-axis analysis demonstrated decreased curvature and decreased wall thickness in the borderzone after MI. These findings are consistent with increased BZM wall stress. However, the long-axis 2DCE analysis demonstrated increased BZM wall thickness and a surprising change in BZM concavity acutely after infarction. The 3DCE analysis confirmed these findings and added additional information regarding regional variability in BZM geometry that was not evident in the two orthogonal 2D views. CONCLUSIONS: This study provides evidence that regional changes in BZM geometry are more complex than previously believed and are not necessarily indicative of increased regional stress. The superiority of 3DCE over 2DCE for assessing these changes is strongly supported.

Animals↗

PubMed2005

Surgical treatment of ischemic mitral regurgitation might not influence ventricular remodeling.

OBJECTIVES: Surgical treatment for ischemic mitral regurgitation has become more aggressive. However, no clinical study has demonstrated that surgical correction of chronic ischemic mitral regurgitation improves survival. We used 4 well-developed ovine models of postinfarction left ventricular remodeling to test the hypothesis that ischemic mitral regurgitation does not significantly contribute to postinfarction left ventricular remodeling. METHODS: Infarction of 21% to 24% of the left ventricular mass was induced by means of coronary ligation in 77 sheep. Infarctions varied only by anatomic location in the left ventricle: anteroapical, n = 26; anterobasal, n = 16; laterobasal, n = 9; and posterobasal, n = 20. Six additional sheep had ring annuloplasty before posterobasal infarction. End-systolic and end-diastolic left ventricular volume, end-systolic muscle-to-cavity area ratio, left ventricular sphericity, ejection fraction, and degree of ischemic mitral regurgitation, as determined by means of quantitative echocardiography, were assessed before infarction and at 2, 5, and 8 weeks after infarction. RESULTS: All infarcts resulted in significant postinfarction remodeling and decreased ejection fraction. Anteroapical infarcts lead to left ventricular aneurysms. Only posterobasal infarcts caused severe and progressive ischemic mitral regurgitation. Remodeling because of posterobasal infarcts was not more severe than that caused by infarcts at other locations. Furthermore, prophylactic annuloplasty prevented the development of mitral regurgitation after posterobasal infarction but had no effect on remodeling. CONCLUSION: The extent of postinfarction remodeling is determined on the basis of infarct size and location. The development of ischemic mitral regurgitation might not contribute significantly to adverse remodeling. Ischemic mitral regurgitation is likely a manifestation rather than an important impetus for postinfarction remodeling.

Animals↗

PubMed2004

Prevention of ischemic mitral regurgitation does not influence the outcome of remodeling after posterolateral myocardial infarction.

OBJECTIVES: This study was designed to test the hypothesis that ischemic mitral regurgitation (IMR) results from, but does not influence, the progression of left ventricular (LV) remodeling after posterolateral infarction. BACKGROUND: Surgical correction of chronic IMR is being increasingly recommended. METHODS: Three groups of sheep had coronary snares placed around the second and third obtuse marginal coronary arteries. Occlusion of these vessels in the control group resulted in progressive IMR over eight weeks. In a second group, Merseline mesh was fitted to cover the exposed LV before infarction. In a third group, a ring annuloplasty was placed before infarction to prevent IMR. Remodeling and degree of IMR were assessed with echocardiography at baseline and at 30 min and two, five, and eight weeks after infarction. RESULTS: Eight weeks after infarction, mean IMR grade was significantly higher in control animals than mesh and annuloplasty animals. At eight weeks, LV end-systolic volume and end-systolic muscle-to-cavity-area ratio (ESMCAR) were significantly better in mesh-treated sheep than in control sheep; also, at eight weeks, ESMCAR and akinetic segment length were significantly better in mesh-treated sheep than in annuloplasty sheep. Ejection fraction was significantly higher in the mesh than the annuloplasty group. There was no significant difference in any measure of remodeling between the annuloplasty and control groups. CONCLUSIONS: Prophylactic ventricular restraint reduces infarct expansion, attenuates adverse remodeling, and reduces IMR severity. Prevention of IMR by prophylactic ring annuloplasty does not influence remodeling. Ischemic mitral regurgitation is a consequence, not a cause, of postinfarction remodeling; infarct expansion is the more important therapeutic target.

Animals↗

PubMed2004

Influence of inotropy and chronotropy on the mitral valve sphincter mechanism.

BACKGROUND: This study was designed to isolate and quantify the effects of ventricular inotropic and chronotropic state on the normal mitral valve annular sphincter mechanism. METHODS: Sonomicrometry tansducers were placed around the mitral annulus in six sheep; atrial pacing wires were also placed. One week later, esmolol was titrated to produce a baseline hemodynamic state with a heart rate of 90 bpm; hemodynamic and sonomicrometry data were recorded. Then animals were paced at 120 bpm and 150 bpm; data were recorded at each heart rate. Isoproterenol infusion was titrated to achieve a heart rate, without pacing, of 120 and 150 bpm; again, data were recorded. Annular area was calculated at end diastole (ED) and end systole (ES) for all experiments using sonomicrometry array localization. Analysis of variance was used to assess the independent effects of heart rate and inotropic state on annular area. RESULTS: Atrial pacing at 120 bpm produced ES and ED annular areas of 777 +/- 150 mm(2) and 748.8 +/- 140.1 mm(2), respectively. At the same heart rate, isoproterenol-treatment resulted in significantly smaller ES and ED areas: 699 +/- 160 mm(2) and 641.9 +/- 156.5 mm(2), respectively. Atrial pacing at 150 bpm produced ES and ED annular areas of 745.2 +/- 131.3 mm(2) and 723.7 +/- 141.3 mm(2), respectively. At the same heart rate, isoproterenol-treatment resulted in significantly smaller ES and ED areas: 652.8 +/- 146.4 mm(2) and 569.7 +/- 155.9 mm(2), respectively. CONCLUSIONS: The inotropic state of the left ventricle directly affects the mitral valve annular orifice area, independent of heart rate. This inotropic effect on valve size is more pronounced at ED than at ES in the sheep.

Adrenergic beta-Agonists↗

PubMed2004

The dynamic anterior mitral annulus.

BACKGROUND: The anterior mitral annulus is considered a fixed structure. Recent data suggest otherwise. This study tested the hypothesis that the size of the anterior annulus varies with hemodynamic loading and ventricular contractility. METHODS: Sonomicrometry array localization measured annular area, total annular circumference, anterior circumference, and posterior circumference in 6 sheep before and after neosynephrine increased systolic blood pressure by at least 150% during atrial pacing at 120 beats/min. In 6 additional animals the same dimensions were measured during atrial pacing (at 120 and 150 beats/min) and during isoproteronol infusions to increase heart rate to 120 and 150 beats/min. RESULTS: Neosynephrine increased systolic total annular circumference from 99.7 +/- 5.5 mm to 106.9 +/- 9.6 mm. Anterior circumference increased from 40.8 +/- 4.0 mm to 45.3 +/- 5.7 mm whereas posterior circumference only increased from 59.0 +/- 5.5 mm to 61.6 +/- 7.0 mm. Low isoproteronol infusion decreased systolic total annular circumference from 107.5 +/- 8.3 mm to 101.9 +/- 10.6 mm. Most of this change occurred in the posterior circumference. Higher infusions of isoproteronol decreased total annular circumference from 106.8 +/- 8.3 mm to 98.3 +/- 9.7 mm. At this higher inotropic state the decrease in annular size was similar in the anterior and posterior annulus. CONCLUSIONS: In sheep, the anterior annulus is a dynamic structure that varies in size in response to changes in hemodynamic loading and ventricular contractility.

Adrenergic beta-Agonists↗

PubMed2004

The effect of regional ischemia on mitral valve annular saddle shape.

BACKGROUND: The mitral valve annulus has a distinctive saddle shape. Recent finite element analysis indicates this shape may contribute to normal valve function by increasing leaflet curvature and reducing leaflet stress. This study tests the hypothesis that acute ischemic mitral regurgitation (AIMR) is associated with loss of annular saddle shape. METHODS: Sonomicrometry array localization (SAL) measured the three-dimensional geometry of the mitral annulus in 6 sheep before and after 30 min of posterior ischemia that produced severe AIMR. Using this SAL data the annular height to commissural width ratio (AHCWR), a measure of annular saddle shape, was calculated throughout the cardiac cycle and reported as a percentage. RESULTS: The normal mitral annulus accentuated its saddle shape rapidly during isovolemic contraction: AHCWR increased from 11.6% +/- 1.1%-13.9% +/- 1.6% (p < 0.001). During ejection AHCWR remained relatively constant ranging from a minimum of 14.1% +/- 1.5% to a maximum of 14.9% +/- 1.3%. During ischemia AHCWR was found to be significantly smaller (p < 0.05) during isovolemic contraction, ejection, and isovolemic relaxation, but not during diastolic filling. Whereas ischemia did not affect AHCWR at end diastole (11.6% +/- 2.8%), the isovolemic accentuation of the saddle shape was lost. CONCLUSIONS: The normal mitral annulus accentuates its saddle shape during systole. This accentuation is eliminated during ischemia that causes AIMR. These data suggest an association between annular saddle shape and valve competency.

Animals↗

PubMed2004

[Observation of the right atrial wall suture line after tricuspid valve supra-annular implantation].

Strength of the right atrial wall suture line after tricuspid valve supra-annular implantation (TVSI) is controversial. We observed the right atrial supra-annular position of a 63-year-old male during his third mitral operation who underwent mitral valve replacement (MVR) and TVSI 15 years ago. Eight years later, he received the second MVR and removal of the bioprosthetic valve from the tricuspid position due to primary tissue failures. The annular size of the tricuspid valve had decreased enough to be fixed by tricuspid annuloplasty (TAP) and re-TVSI was not needed at that time. In this operation, 7 years following bioprosthetic valve removal, the circularly bulging atrial wall still remained and seemed to have enough strength for holding the prosthetic valve. This finding may support the conclusion that the right atrial wall has enouth strength for holding a prosthetic valve in position.

Bioprosthesis↗

PubMed2003

Activated neutrophils and platelet microaggregates impede blood filterability through microchannels during simulated extracorporeal circulation.

BACKGROUND: Neutrophil sequestration and platelet microaggregates in organ capillaries have been implicated in the inflammatory response associated with cardiopulmonary bypass. We examined the filterability of neutrophils and platelet microaggregates through silicon microchannels during simulated extracorporeal circulation. We hypothesize that blood contact with artificial surfaces over time decreases the ability of neutrophils, platelets, and their aggregates to pass through microchannels. METHODS: Fresh human blood from donors (n = 9) was recirculated for 120 minutes in a simulated extracorporeal circuit. Blood samples were obtained from a donor at 0, 30, 60, and 120 minutes of recirculation. The microchannel transit time and the flow behavior of blood cells were evaluated by a silicon microchannel array flow analyzer. CD11b, L-selectin, and F-actin of neutrophils were measured by flow cytometry. Neutrophil and platelet counts and platelet aggregation to adenosine diphosphate were measured. RESULTS: The microchannel transit time was prolonged during recirculation, reaching 185.9% +/- 25.6% of baseline at 120 minutes. The video microscope showed that neutrophils and platelet microaggregates plugged the microchannels. CD11b, L-selectin, and F-actin levels changed significantly by 120 minutes. Platelet counts decreased and platelet aggregability was attenuated. CONCLUSIONS: Simulated extracorporeal circulation caused a progressive loss in the ability of neutrophils, platelets, and their aggregates to pass through the microchannels independent of neutrophil adhesion molecule expression.

Actins↗

PubMed2003

ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation.

BACKGROUND: Among the serine proteases, neutrophil elastase is a powerful cytotoxic enzyme and plays a pivotal role in the inflammatory response associated with cardiopulmonary bypass. This study assesses the effects of the specific inhibition of neutrophil elastase by a novel, potent, low-molecular-weight neutrophil elastase inhibitor, ONO-6818. We hypothesized that ONO-6818 reduces inflammatory mediators and modulates adhesion molecules and the deformability of neutrophils during simulated extracorporeal circulation. METHODS: Simulated extracorporeal circulation was established by recirculating fresh heparinized (3.75 U/mL) human blood for 120 minutes in a membrane oxygenator and a roller pump with and without 1.0 micromol/L of ONO-6818 (n = 9 for control group, n = 7 for ONO-6818 group). The neutrophil adhesion molecules, CD11b and L-selectin, and the cytoplasmic F-actin of neutrophils were measured by flow cytometry. Neutrophil deformability was evaluated using simulated silicon microcapillaries. Neutrophil elastase, interleukin 8, and C5b-9 were measured using enzyme immunoassay. RESULTS: Neutrophil elastase levels were significantly lower in the ONO-6818 group. ONO-6818 significantly reduced interleukin 8 and C5b-9 production. ONO-6818 did not modulate changes of CD11b and L-selectin during recirculation. Cytoplasmic F-actin content and changes of neutrophil deformability did not significantly differ between the groups. CONCLUSIONS: Inhibition of neutrophil elastase activity with ONO-6818 reduces further interleukin 8 production and the formation of the complement membrane attack complex, and this results in a reduction of neutrophil elastase levels during simulated extracorporeal circulation. This study suggests that specific neutrophil elastase inhibition with ONO-6818 is a feasible therapeutic option to attenuate the exaggerated inflammatory response associated with cardiopulmonary bypass.

Actins↗

PubMed2003

Annuloplasty ring selection for chronic ischemic mitral regurgitation: lessons from the ovine model.

BACKGROUND: Chronic ischemic mitral regurgitation (CIMR) is poorly understood and repair operations are often unsatisfactory. This study elucidates the mechanism of CIMR in an ovine model. METHODS: Sonomicrometry array localization measured the three-dimensional geometry of the mitral annulus and subvalvular apparatus in five sheep before and 8 weeks after a posterior infarction of the left ventricle that produced progressive severe CIMR. RESULTS: End systolic annular area increased from 647 +/- 44 mm(2) to 1,094 +/- 173 mm(2) (p = 0.01). Annular dilatation occurred equally along the anterior (47.0 +/- 5.6 mm to 60.2 +/- 4.9 mm, p = 0.001) and posterior (53.8 +/- 3.1 mm to 68.5 +/- 8.4 mm, p = 0.005) portions of the annulus. The tip of the anterior papillary muscle moved away from both the anterior and posterior commissures by 5.2 +/- 3.2 mm (p = 0.021) and 7.3 +/- 2.2 mm (p = 0.002), respectively. The distance from the tip of the posterior papillary muscle to the anterior commissure increased by 11.0 +/- 5.7 mm (p = 0.032) while the distance from the tip of the posterior papillary muscle to the posterior commissure remained constant. CONCLUSIONS: Progressive dilatation of both the anterior and posterior mitral annuli, increased annular area, and asymmetric ventricular dilatation combine to cause CIMR by distortion of mitral valve geometry and tethering of leaflet coaptation. Therefore complete ring annuloplasty may be superior to partial annuloplasty in the treatment of CIMR.

Animals↗