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Objective: Finite-element analysis demonstrates that the nonplanar shape of the mitral annulus diminishes mitral leaflet stress. It has therefore been postulated that repair with annuloplasty rings that maintain the nonplanar shape of the annulus could increase repair durability. Although the global nonplanarity of the mitral annulus has been adequately characterized, design of such a ring requires a quantitative description of regional annular geometry. By using real-time 3-dimensional echocardiography in conjunction with available image processing software, we developed a methodology for describing regional annular geometry and applied it to the characterization of the normal human mitral annulus., Methods: Five healthy volunteers underwent mitral valve imaging with real-time 3-dimensional echocardiography. Regional annular height was calculated at 36 evenly spaced intervals., Results: Maximal annular height/commissural width ratio was found to occur at the midpoint of the anterior annulus in all cases. These values averaged 26% +/- 3.1%, whereas those for the midposterior annulus averaged 18% +/- 3.0%. The average commissural width was 35.2 +/- 6.0 mm. Although substantial spatial heterogeneity was observed, regional annular height at a given rotational position was highly conserved among subjects when normalized to commissural width., Conclusions: These quantitative imaging and analytic techniques demonstrate that the normal human mitral annulus is regionally heterogeneous in its nonplanarity, and they establish a means of describing annular geometry at a regional level. With wider application, these techniques may be used both to characterize pathologic annular geometry and to optimize the design of mitral valve annuloplasty devices.

It is widely accepted that, during acute coronary occlusion, ischemic cell death progresses from the subendocardium to the subepicardium in a wavefront fashion. This concept, which implies that the subendocardium is the most susceptible myocardial region to ischemic injury, was established using a canine model with an extensive system of subepicardial coronary collaterals. In humans, particularly in those with coronary artery disease, there is a wide range in the distribution and functional capacity of the collateral circulation, which may affect the pattern of infarct evolution. Using an ovine model with a limited system of preformed subendocardial coronary collaterals, we characterized the effect of increasing lengths of ischemia on regional blood flow and infarct size in three regions of the ventricular wall: subendocardium, midmyocardium, and subepicardium. Our results demonstrate that the myocardium and microvasculature in these three regions are equally susceptible to injury after 45 min of ischemia. When ischemic time is increased to 1 h, infarct size in the midmyocardium (90 +/- 2%) is greater than in the subendocardium (76 +/- 4%, P = 0.004) and subepicardium (84 +/- 3%, P = 0.13). Microvascular dysfunction as assessed as a percentage of baseline flow is also greater in the midmyocardium (14 +/- 5%) compared with the subendocardium (20 +/- 3%, P = 0.23) and subepicardium (51 +/- 9%, P = 0.007). These findings suggest that, in subjects with a limited system of coronary collateral circulation, the midmyocardium is the most susceptible myocardial region to ischemia and the subendocardium is the most resistant. Myocardial viability during coronary occlusion appears to be primarily determined by the distribution and functional capacity of the collateral circulation.

Background: The mammalian mitral annulus is saddle shaped. Experimental studies have shown that loss of saddle shape occurs in ischemic mitral regurgitation. However, neither the temporal pattern of global annular remodeling nor the geometric pattern of regional annular remodeling has been described. We sought to characterize these changes using real-time three-dimensional echocardiography in an ovine model., Methods: Ten sheep underwent real-time three-dimensional echocardiography at baseline and 1 hour and 8 weeks after posterobasal myocardial infarction. Multiple mitral annular geometric indexes were measured at each time point to assess regional and global annular remodeling., Results: One hour after infarction, global annular height decreased from 5.8 +/- 0.5 mm to 4.0 +/- 0.4 mm (p < 0.001) while intercommissural width increased from 29.0 +/- 1.3 mm to 35.7 +/- 1.7 mm (p = 0.023), resulting in a decrease in the global annular height to commissural width ratio from 20.0% +/- 1.6% to 11.2% +/- 0.9% (p < 0.001). Eight weeks after infarction, global annular height decreased to 3.9 +/- 0.2 mm (p < 0.05) while intercommissural width increased to 40.7 +/- 1.5 mm (p < 0.001), resulting in an additional decrease in the global annular height to commissural width ratio to 9.4% +/- 0.4% (p < 0.001). Although annular remodeling involved the entire mitral annulus, there was regional heterogeneity in its extent., Conclusions: Significant global annular flattening and dilatation occur during the development of ischemic mitral regurgitation in an ovine model. Regional annular remodeling is heterogeneous and is not limited the posterior commissure or the posterior annulus.

Objective: The mechanisms contributing to ascending thoracic aortic aneurysms associated with bicuspid aortic valves may differ from ascending thoracic aortic aneurysms with tricuspid aortic valves. Matrix metalloproteinases and their endogenous inhibitors have been causally linked to ascending thoracic aortic aneurysm formation. This study tested the hypothesis that specific and different matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles would be observed in ascending thoracic aortic aneurysm samples from patients with bicuspid aortic valves versus tricuspid aortic valves., Methods: Ascending thoracic aortic aneurysm samples taken from patients with bicuspid aortic valve (n = 53) and patients with tricuspid aortic valve (n = 46) were assessed for representative subtypes of all matrix metalloproteinase classes and all 4 known tissue inhibitors of metalloproteinases. Levels were compared [optical density units, median (interquartile range)] both to reference control ascending aortic samples (n = 26) and within each valve group by aneurysm diameter (< or =3.9 cm, 4.0-5.9 cm and > or =6.0 cm)., Results: Different and specific matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles were observed in the ascending thoracic aortic aneurysm groups. In bicuspid aortic valves, matrix metalloproteinase-2 increased by 34% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-14 decreased by 59% compared with tricuspid aortic valves (P < .05). In tricuspid aortic valve samples, tissue inhibitors of metalloproteinase-2 decreased by 35% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-13 increased by 140% in the 4.0- to 5.9-cm diameter range (P < .05)., Conclusions: A unique matrix metalloproteinase and tissue inhibitor of metalloproteinase portfolio was observed in ascending thoracic aortic aneurysms from patients with bicuspid aortic valve compared with patients with tricuspid aortic valve. These differences, suggesting disparate mechanisms of extracellular matrix remodeling, may provide unique biochemical targets for ascending thoracic aortic aneurysm prognostication and treatment in these 2 groups of patients.

Background: Aortic valve stenosis is the most frequent indication for valve replacement surgery, and is commonly associated with pathologic calcification. Previous investigations by our group have shown a strong association of transforming growth factor-beta1 (TGF-beta1)-related mechanisms with calcific aortic stenosis in both cell culture and clinical pathology studies., Methods: In the present investigations we sought to investigate the sequence of events involved in TGF-beta1-initiated aortic valve interstitial cell calcification in cell culture, and to study related gene expression pattern differences comparing calcific aortic stenosis surgical specimens with normal aortic valve leaflets., Results: Sheep aortic valve interstitial cells (SAVIC) in culture progressively calcified over 14 days after the addition of TGF-beta1 to a significantly greater extent than non-TGF-beta1 controls. The TGF-beta1-induced SAVIC calcification was associated with maximal levels of alkaline phosphatase by 72 hours. Annexin V positive apoptosis was increased in TGF-beta1-treated SAVIC cultures at 14 days compared with controls. Matrix metalloproteinase 9 per gel zymography was detectable only in SAVIC cultures treated with TGF-beta1 from seven days on. Matrix metalloproteinase 2 was present in all SAVIC cultures per gel zymograms, either with or without TGF-beta1, but the active form of matrix metalloproteinase 2 significantly increased over 14 days in response to TGF-beta1. Quantitative gene expression studies (re: RNA levels) of human aortic valve cusps obtained at cardiac surgery demonstrated a number of related trends, including upregulation of the expression of TGF-beta1, alkaline phosphatase, and matrix metalloproteinase 9 in calcified human aortic valves., Conclusions: Transforming growth factor-beta1 causes SAVIC to calcify due to an early maximal increase in alkaline phosphatase activity with associated apoptotic events and increased matrix metalloproteinase 9. These TGF-beta1-related mechanistic events may be of clinical relevance based upon the gene expression pattern changes observed in calcific aortic stenosis valve cusps.

Heart valve replacements fabricated from glutaraldehyde (Glut)-crosslinked heterograft materials, porcine aortic valves or bovine pericardium, have been widely used in cardiac surgery to treat heart valve disease. However, these bioprosthetic heart valves often fail in long-term clinical implants due to pathologic calcification of the bioprosthetic leaflets, and for stentless porcine aortic valve bioprostheses, bioprosthetic aortic wall calcification also typically occurs. Previous use of the epoxide-based crosslinker, triglycidyl amine (TGA), on cardiac bioprosthetic valve materials demonstrated superior biocompatibility, mechanics, and calcification resistance for porcine aortic valve cusps (but not porcine aortic wall) and bovine pericardium, vs. Glut-prepared controls. However, TGA preparation did not completely prevent long-term calcification of cusps or pericardium. Herein we report further mechanistic investigations of an added therapeutic component to this system, 2-mercaptoethylidene-1,1-bisphosphonic acid (MABP), a custom synthesized thiol bisphosphonate, which has previously been shown in a preliminary report to prevent bioprosthetic heterograft biomaterial calcification when used in combination with initial TGA crosslinking for 7 days. In the present studies, we have further investigated the effectiveness of MABP in experiments that examined: (1) The use of MABP after optimal TGA crosslinking, in order to avoid any competitive interference of MABP-reactions with TGA during crosslinking; (2) Furthermore, recognizing the importance of alkaline phosphatase (ALP) in the formation of dystrophic calcific nodules, we have investigated the hypothesis that the mechanism by which MABP primarily functions is through the reduction of ALP activity. Results from cell-free model systems, cell culture studies, and rat subcutaneous implants, show that materials functionalized with MABP after TGA crosslinking have reduced ALP activity, and in vivo have no significant calcification in long-term implant studies. It is concluded that bioprosthetic heart valves prepared in this fashion are compelling alternatives for Glut-prepared bioprostheses.

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.

Fluorometry is used to detect intrinsic flavoprotein (FP) and nicotinamide adenine dinucleotide (NADH) signals in an open-chest rabbit model of myocardial ischemia-reperfusion injury. Myocyte apoptosis has been shown clinically to contribute to infarct size following reperfusion of ischemic myocardium. A noninvasive means of assessing apoptosis in this setting would aid in the treatment of subsequent ventricular remodeling. We show that in vivo fluorometry can be useful in apoptosis detection in open-chest surgeries. Specific changes in myocardial redox states have been shown to indicate the presence of apoptosis. Two main mitochondrial intrinsic fluorophores, NADH and FP signals, were measured during normoxia, ischemia, and reperfusion experimental protocol. Ischemia was induced by occlusion of the largest branch of the circumflex coronary artery and fluorescence signals are collected by applying two different fluorescence techniques: in vivo fluorometry and postmortem cryoimaging. The first technique was employed to detect FP and NADH signals in vivo and the latter technique uses freeze trapping and low-temperature fluorescence imaging. The heart is snap frozen while still in the chest cavity to make a "snapshot" of the metabolic state of the tissue. After freezing, the ischemic area and its surrounding border zone were excised and the sample was embedded in a frozen buffer for cryoscanning. These two data sets, in vivo fluorometry and low-temperature redox scanning, show consistent extreme oxidation of the mitochondrial redox states (higher redox ratio) suggesting the initiation of apoptosis following reperfusion. This represents the first attempt to assess myocyte apoptosis in the beating heart.

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.

Acetaminophen, the active ingredient in Tylenol, is a widely used drug that is well known for its analgesic and antipyretic properties. Acetaminophen is a commonly used alternative to nonsteroidal anti-inflammatory drugs, which have recently been demonstrated to increase mortality after acute myocardial infarction (AMI). The safety and potential cardioprotective properties of acetaminophen in the setting of AMI have recently been investigated; however, the results from these studies have been inconclusive. Using both large (ovine) and small (rabbit) collateral-deficient animal models, we studied the effects of acetaminophen in the setting of reperfused AMI. In both species we studied the effects of acetaminophen on myocardial salvage and ventricular function. Additionally, we studied the effects of acetaminophen on myocardial perfusion in sheep and on myocyte apoptosis in rabbits. Sixteen sheep and twenty-two rabbits were divided into two groups and administered acetaminophen or a vehicle before undergoing ischemia and reperfusion. The ischemic period was 60 min in sheep and 30 min in rabbits. All animals were reperfused for 3 h. There were no significant differences observed in myocardial perfusion, myocyte apoptosis, or infarct size in acetaminophen-treated animals. Acetaminophen increased cardiac output and mean arterial pressure before ischemia in sheep but had no effect on any other hemodynamic parameter. In rabbits, no effect on cardiac output or blood pressure was detected. These results support the role of acetaminophen as a safe drug in the postmyocardial infarction setting; however, no significant cardioprotective effect of the drug could be demonstrated.

Five million Americans suffer from heart failure. Despite innovative new pharmacologic and device therapy, the 5-year mortality rate for these patients remains near 50%. Conservatively, 300,000 patients with heart failure also have severe functional mitral regurgitation. Over the past decade the surgical approach to these patients has become more aggressive as the extent of the problem has become widely recognized and surgeon familiarity with annuloplasty techniques has increased. There are, however, few data to support that such interventions improve longevity, reduce heart size, or limit symptoms. In fact the best available data support the conclusion that surgery for functional mitral regurgitation has no effect on survival. We present a review of the existing data on the efficacy of mitral valve surgery in heart failure patients. These data are sobering but confirm the need for evidence-based decision-making in cardiac surgery no matter how intuitively beneficial a procedure may initially seem.

Although three-dimensional (3D) echocardiography is still in its evolution, cutting edge advances that allow quantifiable images of cardiac structures to be created in real-time will begin to increase its use drastically. One of the most promising uses of the technology is in the planning, optimization, and postoperative surveillance of mitral valve repair techniques and devices. This article reviews the development of 3D echocardiography and presents illustrations of how it may be applied to improving mitral valve repair techniques. It is conceivable in the near future that mitral repair procedures will be designed and customized for each patient preoperatively using data obtained from 3D echo images and computerized virtual surgery techniques. Such tools will allow the surgeon to design operations that thoroughly analyze valve geometry and stress distribution before ever entering the operating room.

Background: Assessment of left ventricular (LV) function with an emphasis on contractility has been a challenge in cardiac mechanics during the recent decades. The LV function is usually described by the LV pressure-volume (P-V) relationship. Based on this relationship, the ratio of instantaneous pressure to instantaneous volume is an index for LV chamber stiffness. The standard P-V diagrams are easy to interpret but difficult to obtain and require invasive instrumentation for measuring the corresponding volume and pressure data. In the present study, we introduce a technique that can estimate viscoelastic properties, not only the elastic component but also the viscous properties of the LV based on oscillatory behavior of the ventricular chamber and it can be applied non-invasively as well., Materials and Methods: The estimation technique is based on modeling the actual long axis displacement of the mitral annulus plane toward the cardiac base as a linear damped oscillator with time-varying coefficients. Elastic deformations resulting from the changes in the ventricular mechanical properties of myocardium are represented as a time-varying spring while the viscous components of the model include a time-varying viscous damper, representing relaxation and the frictional energy loss. To measure the left ventricular axial displacement ten healthy sheep underwent left thoracotomy and sonomicrometry transducers were implanted at the apex and base of the LV. The time-varying parameters of the model were estimated by a standard Recursive Linear Least Squares (RLLS) technique., Results: LV stiffness at end-systole and end-diastole was in the range of 61.86-136 dyne/gxcm and 1.25-21.02 dyne/gxcm, respectively. Univariate linear regression was performed to verify the agreement between the estimated parameters, and the measured values of stiffness. The averaged magnitude of the stiffness and damping coefficients during a complete cardiac cycle were estimated as 58.63+/-12.8 dyne/gxcm and 0 dynexs/gxcm, respectively., Conclusion: The results for the estimated elastic coefficients are consistent with the ones obtained from force-displacement diagram. The trend of change in the estimated parameters is also in harmony with the previous studies done using P-V diagram. The only input used in this model is the long axis displacement of the annulus plane, which can also be obtained non-invasively using tissue Doppler or MR imaging.

Assessment of left ventricular (LV) function with an emphasis on contractility has been a challenge in cardiac mechanics during the recent decades. The LV function is usually described by the LV pressure-volume (P-V) diagram. The standard P-V diagrams are easy to interpret but difficult to obtain and require invasive instrumentation for measuring the corresponding volume and pressure data. In the present study, we introduce a technique that can estimate the viscoelastic properties of the LV based on harmonic behavior of the ventricular chamber and it can be applied non-invasively as well. The estimation technique is based on modeling the actual long axis displacement of the mitral annulus plane toward the cardiac base as a linear damped oscillator with time-varying coefficients. The time-varying parameters of the model were estimated by a standard recursive linear least squares (RLLS) technique. LV stiffness at end-systole and end diastole was in the range of 61.86-136.00 dyne/g.cm and 1.25-21.02 dyne/g.cm, respectively. The only input used in this model was the long axis displacement of the annulus plane, which can also be obtained non-invasively using tissue Doppler or MR imaging.

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.

Background: Early infarct expansion impairs function of normally perfused borderzone myocardium (BZM), initiates adverse remodeling, and portends a poor long-term outcome. Early ventricular restraint has been demonstrated to improve global remodeling but its effect on BZM function has not been assessed. Using an ovine model of infarct induced remodeling and MRI, we tested the hypothesis that ventricular restraint early after MI preserves BZM function and reduces remodeling., Methods: Six sheep had a large anterior infarction after ligation of all diagonal branches. One week after infarction 3 sheep had placement of a cardiac support device (CSD) to restrain infarct expansion. Global remodeling and borderzone wall thickening strain were assessed using tagged MRI before and 8 weeks after infarction., Results: Global remodeling was greatly reduced in the CSD group compared with control. The BZM systolic wall thickening was similar in both groups at baseline (13.5% +/- 2.0%, control; 12.8% +/- 2.0%, CSD, p = 0.8). After 8 weeks of infarction-induced remodeling, systolic wall thickening strain decreased significantly to 4.9% +/- 0.7% in the control group (p = 0.03). In contrast, systolic wall thickening was preserved in the CSD group at 8 weeks (11.0% +/- 1.6%, p = 0.3). In the control group all thickening occurred during isovolemic contraction, plateauing during ejection. The CSD improved late systolic borderzone wall thickening, although dynamics remained perturbed., Conclusions: Ventricular restraint early after MI improves both contractile function of the BZM and global ventricular remodeling. The dynamics of BZM wall thickening are impaired during remodeling. The CSD significantly improves but does not completely maintain baseline BZM wall thickening dynamics.

Background: Whether mechanical restraint of the left ventricle (LV) can influence remodeling following myocardial infarction (MI) remains poorly understood. The following discussion details three studies examining the effects of surgically placing a cardiac support device (CSD) over the entire epicardial surface, on infarct expansion, global cardiac function and myocyte geometry and function post-MI., Methods: The effects of passive constraint on infarct expansion and global cardiac function/myocardial energetics were investigated in 10 sheep (5 MI only; 5 MI + CSD) using pressure-volume analysis and magnetic resonance imaging (MRI). Additionally, 11 sheep (5 MI only; 6 MI + CSD) were used to study the effects of passive restraint on myocyte geometry and function post-MI, with 10 additional uninstrumented sheep serving as controls. Baseline data was collected followed by the creation of an anterior infarct. 1 week post-infarct the animals underwent a second set of data collection studies followed by placement of the CSD in the experimental groups. Additional data was collected at 2 and 3 months post-MI. The animals in the myocyte function group underwent additional studies immediately following the 3 month time point., Results: Infarct expansion was diminished as a result of the CSD. At 1 week post-MI the akinetic area was similar in both groups. At the terminal time-point, the akinetic area in the control group was similar to the 1-week time-point whereas, in the CSD group, the area of akinesis decreased (P = 0.001). A comparison of the two groups at the terminal time-point demonstrates a significantly diminished area of akinesis in the CSD group (P = 0.004). The relative area of akinesis followed a similar pattern. The CSD group also exhibited a decrease in end-diastolic volume (control 110.3 +/- 19.8 mL vs. CSD 67.6 +/- 4.7 mL, P = .006) and an improved ejection fraction (control 15.5% +/- 5.7% vs. CSD 29.46% +/- 4.42%, P = .008) relative to the control group. Myocardial energetics were also enhanced in the CSD group as evidenced by significant improvements in potential energy (control 2,015 +/- 503 mL x mm Hg/beat vs. CSD 885 +/- 220 mL x Hg/beat, P = .006), efficiency (control 39.4% +/- 13.6% vs. CSD 59.8% +/- 8.5%, P = .044), and oxygen consumption (control 0.072 +/- 0.013 mL O(2)/beat vs. CSD 0.052 +/- 0.007 mL O(2)/beat, P = .034). Isolated LV myocyte shortening velocity was reduced by 35% from control values (P < 0.05) in both MI groups. LV myocyte beta-adrenergic response was reduced with MI, but normalized in the MI + CSD group. Relative collagen content was increased and matrix metalloproteinase-9 was decreased within the MI border region of the CSD group., Conclusions: The CorCap cardiac support device retarded infarct expansion, improved global and regional cardiac function and beneficially modified LV and myocyte remodeling post-MI. These findings provide evidence that non-pharmacological strategies can interrupt adverse LV remodeling post-MI.

Infarcted segments of myocardium demonstrate functional impairment ranging in severity from hypokinesis to dyskinesis. We sought to better define the contributions of passive material properties (stiffness) and active properties (contracting myocytes) to infarct thickening. Using a finite-element (FE) model, we tested the hypothesis that infarcted myocardium must contain contracting myocytes to be akinetic and not dyskinetic. A three-dimensional FE mesh of the left ventricle was developed with echocardiographs from a reperfused ovine anteroapical infarct. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction, and an elastance model for active fiber stress was incorporated. The diastolic stiffness (C) and systolic material property (isometric tension at longest sarcomere length and peak intracellular calcium concentration, T(max)) of the uninfarcted remote myocardium were assumed to be normal (C = 0.876 kPa, T(max) = 135.7 kPa). Diastolic and systolic properties of the infarct necessary to produce akinesis, defined as an average radial strain between -0.01 and 0.01, were determined by assigning a range of diastolic stiffnesses and scaling infarct T(max) to represent the percentage of contracting myocytes between 0% and 100%. As C was increased to 11 times normal (C = 10 kPa) the percentage of T(max) necessary for akinesis increased from 20% to 50%. Without contracting myocytes, C = 250 kPa was necessary to achieve akinesis. If infarct stiffness is <285 times normal, contracting myocytes are required to prevent dyskinetic infarct wall motion.

Background: Myofibrillarlytic (MFL) cells are commonly observed in subendocardial myocardium in myocardial infarction. Because ischemic damage to myocytes is also known to induce apoptosis, we evaluated the prevalence of apoptosis in MFL cells in nine ischemic cardiomyopathic hearts explanted during transplantation., Methods: Myocytes with partial or complete clearing of cytoplasm, observed commonly in the subendocardium, were recognized as MFL cells. Prevalence of apoptosis was defined by TUNEL and ISOL staining and further characterized by immunohistochemical staining for caspase-3, Bcl2, BCL-X(L), Bax, proliferating cell nuclear antigen (PCNA), and Ki67., Results: Of 4131 MFL cells examined, 1305 (32%) possessed nuclei in a given histologic section; 1140 (88%) of the nucleated myocardial cells were TUNEL positive. Of 842 cells with normal appearance, 257 (31%) cells demonstrated nuclei in the given histologic section. TUNEL staining was observed in 5 (1.9%) in these control areas. All MFL cells stained positive for caspase 3. The antiapoptotic proteins, Bcl2 and BCL-X(L), demonstrated intense upregulation within and surrounding MFL cells, whereas pro-apoptotic protein Bax expression was only seen at control level. The MFL cells had Ki67 negative and PCNA positive nuclei., Conclusions: The present study demonstrates that the majority of MFL cells are apoptotic and are associated with upregulation of caspase 3. Simultaneous upregulation of Bcl2 represents a survival effort in these myocytes. This is consistent with the review of the literature that MFL cells are viable, persist in myocardium for long time and may be functionally reversible. Evidence for concurrent apoptosis and survival instinct represent a conceptual paradox and suggests that myocytes undergoing apoptosis should be amenable to reconstitution of function.

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.

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.

Background: Surgical anterior ventricular restoration (SAVER) has been proposed for dilated ischemic cardiomyopathy with an akinetic distal anterior left ventricular wall. We tested the hypothesis that SAVER increases stroke volume, reduces mean myofiber stress and achieves optimal results without a patch., Methods: A finite element model of the left ventricle (LV) with an akinetic but contractile anteroapical LV wall segment was used. Separate versions of the model with normal and dilated LV sizes were developed and used to simulate the SAVER operation with and without a patch of varying stiffness from 10 to 100 kilopascals., Results: The SAVER operation reduced myofiber stress in the akinetic infarct and infarct borderzone, but caused a reduction in the Starling relationship. In all cases, stroke volume decreased while ejection fraction increased after SAVER. The SAVER operation was more beneficial in dilated ventricles, and the reduction in stroke volume after SAVER without patch was minimal. The effect of patch stiffness was mixed as stiffer material causes a greater reduction in stress yet has the greatest negative effect on stroke volume., Conclusions: These simulations support the use of SAVER in dilated hearts without a patch.

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.

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.

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.

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.

Background: Unlike myxomatous degeneration in Marfan syndrome, which has been reported to result from a mutation in the gene that codes for the extracellular structural protein fibrillin, no specific molecular abnormality has been documented to be the underlying cause of myxomatous degeneration in mitral valve prolapse syndrome (MVPS). The present study examined the distribution of fibrillin and other extracellular matrix proteins in patients with isolated MVPS., Methods: Mitral valve leaflets from 7 MVPS patients and 5 rheumatic heart disease (RHD) patients were characterized immunohistochemically for fibrillin, elastin, collagen I, and collagen III distribution, and compared with five normal mitral valves., Results: In normal mitral valve leaflets immunostaining for fibrillin, elastin, collagen I, and collagen III revealed a fibrillary and laminar pattern in the atrialis and the spongiosa. In addition, both the collagens were present in the ventricularis, and the coarse bundles in the fibrosa exhibited alternating bandlike collagen I immunoreactivity. The staining patterns of fibrillin, elastin, and collagens I and III revealed distinctly different distribution in MVPS relative to the normal and RHD leaflets. MVPS leaflets in areas of myxoid degeneration displayed a more diffuse, weaker, and nonlaminar pattern of staining for fibrillin. Similar, but less severe abnormality of elastin, collagen I, and collagen III was also observed. Unlike diffuse abnormality in MVPS, the disruption of extracellular proteins in RHD only occurred at the site of the inflammatory damage, but the overall architecture was preserved., Conclusions: The results of the current study suggest a primary role for abnormal fibrillin and other matrix proteins in producing myxoid degeneration of mitral valve leaflets in MVPS.

Early infarct expansion is associated with progressive ventricular dilatation and contractile dysfunction, and heralds a poor long-term prognosis. The pathophysiology of ventricular remodeling leading to CHF is hypothesized to begin with infarct expansion, which causes increased stress in the myocardium adjacent to the infarct. Increased stress in normally perfused border zone myocardium results in the production of cytokines and ROS, which in turn stimulate myocyte apoptosis, disruption of the ECM, and fibrosis. The value of ventricular compressive therapy in established CHF with the Acorn CSD is unclear. Early clinical and laboratory studies indicate that the device can be placed safely using standard surgical techniques, and that constrictive physiology is surprisingly rare. In the few patients who have received the device, however, the clinical benefit has not been dramatic. A final assessment awaits a well-designed clinical trial comparing isolated CSD placement with optimal medical management, the primary end points being death or the need for organ replacement. In contrast, the value of early ventricular compressive therapy (ie, the prophylactic prevention of infarct expansion) has been demonstrated experimentally: early ventricular restraint dramatically ameliorates remodeling. This strategy probably represents the best application of ventricular compressive therapy. Future work must ascertain the best timing for such an intervention.

The course of cardiac remodeling after an acute cardiac MI, might affect the orientation of the cardiac muscle fibers as well as their contraction behavior. This may result in alteration of the untwisting during isovolumic relaxation phase, which might have effects on rapid early filling phase. In the present article, the variation of the time constant of isovolumic pressure drop (tau) has been studied during the course of cardiac remodeling after different types of induced myocardial infarction (MI) in sheep. The results for each group show different patterns of change in tau. The normalized tau curve in all three groups of anteroapical, anterobasal and posterobasal MI group show a rise 30 minutes after infarction. Two weeks later, the pressure drop constants decline to a lower level than baseline and by eight weeks after infarction, the time constant reached around the baseline level.

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.

Gastric necrosis after esophagectomy is a difficult clinical problem. Remedial operations to reestablish gut continuity usually rely on the use of the left colon as the neo-esophagus. Previous resection of the necrotic stomach, adhesions associated with a multiple redo-laparotomy and the need to use a substernal route to reach the cervical esophagus all conspire to produce a requirement for increased conduit length. We present a case in which the "arterial supercharge technique" was used to provide a colonic interposition with extended length in such a clinical situation.

Donor-derived melanoma is easily transmitted through organ transplants and is highly aggressive in transplant recipients. The best treatment-withdrawal or reduction of immunosuppression-permits tumor rejection but risks allograft rejection. In recipients of nonrenal allografts, the prognosis is particularly grim, with transmission rates and mortality approaching 100%. Retransplantation has been proposed as a possible strategy but has never been performed for a cardiac allograft. This is the first report of cardiac retransplantation and only the second case of retransplantation of any nonrenal organ. Our patient received a heart transplant from a donor found to have occult metastatic melanoma at autopsy. He underwent retransplantation 17 days later. Close clinical and radiographic follow-up reveal no evidence of melanoma 22 months after transplantation. Based on the rapid development of donor-derived melanoma in previous reports, our patient is likely to remain free of donor cancer. Retransplantation and low-dose immunosuppression may have been lifesaving.

Acute mitral regurgitation secondary to a ruptured papillary muscle or primary chord, in the setting of profound cardiogenic shock, is one of the more challenging cases in adult cardiac surgery. Some would consider such a clinical situation in an octogenarian futile and, in the current era of health care cost containment, a potential waste of resources. We present two such cases with successful outcomes.

Background: Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region- and type-specific distribution of MMPs occurs within the post-MI myocardium remained unknown., Methods and Results: Ten sheep were instrumented with a sonomicrometry array to measure dimensions in 7 distinct regions corresponding to the remote, transition, and MI regions. Eight sheep served as reference controls. The relative abundance of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was quantified by immunoblotting. Segment length increased from baseline in the remote (24.9+/-5.4%), transition (18.0+/-2.9%), and MI (53.8+/-11.0%) regions at 8 weeks after MI (P<0.05) and was greatest in the MI region (P<0.05). Region- and type-specific changes in MMPs occurred after MI. For example, MMP-1 and MMP-9 abundance was unchanged in the remote, fell to 3+/-2% in the transition, and was undetectable in the MI region (P<0.05). MMP-13, MMP-8, and MT1-MMP increased by >300% in the transition and MI regions (P<0.05). TIMP abundance decreased significantly in the transition region after MI and fell to undetectable levels within the MI region., Conclusions: The unique findings of this study were 2-fold. First, changes in regional geometry after MI were associated with changes in MMP levels. Second, a region-specific portfolio of MMPs was induced after MI and was accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory control. Targeting the regional imbalance between specific MMPs and TIMPs within the post-MI myocardium holds therapeutic potential.

After myocardial infarction (MI), the border zone expands chronically, causing ventricular dilatation and congestive heart failure (CHF). In an ovine model (n = 4) of anteroapical MI that results in CHF, contrast echocardiography was used to image short-axis left ventricular (LV) cross sections and identify border zone myocardium before and after coronary artery ligation. In the border zone at end systole, the LV endocardial curvature (K) decreased from 0.86 +/- 0.33 cm(-1) at baseline to 0.35 +/- 0.19 cm(-1) at 1 h (P < 0.05), corresponding to a mean decrease of 55%. Also in the border zone, the wall thickness (h) decreased from 1.14 +/- 0.26 cm at baseline to 1.01 +/- 0.25 cm at 1 h (P < 0.05), corresponding to a mean decrease of 11%. By Laplace's law, wall stress is inversely proportional to the product K. h. Therefore, a 55% decrease in K results in a 122% increase in circumferential stress; a 11% decrease in h results in a 12% increase in circumferential stress. These findings indicate that after MI, geometric changes cause increased dynamic wall stress, which likely contributes to border zone expansion and remodeling.

Endomyocardial injection of adenoviral gene vectors enables localized delivery to comprised myocardial tissue. However, many materials used in endomyocardial delivery catheters may not be compatible with adenoviral gene vectors. In this study, a series of catheter-based endocardial and epicardial (direct visualization) procedures were performed to assess catheter-adenovirus compatibility in an in vivo model. A standard Nitinol-stainless steel (Ni-SS) catheter was compared with a novel Stiletto catheter designed for improved biocompatibility. In 4 animals 40 endocardial injections of adenovirus encoding beta-galactosidase (beta-Gal) were performed with the 2 catheters. After sectioning of the hearts only 8 of 20 Ni-SS beta-Gal+ sites could be identified (40% retrieval) whereas 16 of the 20 Stiletto injection sites were identified (80%). Within these areas successful transfection was observed (12.2 +/- 4.0 beta-Gal+ cells/high-power field [HPF] in the Ni-SS group vs. 30.1 +/- 6.8 beta-Gal+ cells/HPF in the Stiletto group; p = 0.03). After epicardial delivery to distinct areas of the myocardium adenoviral delivery as assayed by beta-galactosidase protein activity was >21 +/- 16-fold (range, 5 to >43-fold) greater than after Stiletto delivery. In conclusion, this study highlights the importance of adenovirus-material compatibility in gene delivery to the myocardium. Efficiency was greater when using the catheter designed to enhance biocompatibility.

Background: Acute type A dissections require surgery to prevent death from proximal aortic rupture or malperfusion. Most series over the past decade have reported a death rate in the range of 15% to 30%. The objective of this study is to examine the effect of an integrated surgical approach on the treatment of acute type A dissections., Methods: From January 1994 to April 2002, 163 consecutive patients underwent repair of acute type A dissection. All had an integrated operative management as follows: intraoperative transesophageal echocardiography; hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion to replace the aortic arch; HCA established after 3 minutes of electroencephalographic silence in neuromonitored patients (60%) or after 45 minutes of cooling in patients who were not neuromonitored (40%); reinforcement of the residual arch tissue with a Teflon felt "neo-media;" cannulation of the arch graft to reestablish cardiopulmonary bypass at the completion of HCA (antegrade graft perfusion); and remodeling of the sinus of Valsalva segments with Teflon felt "neo-media" and aortic valve resuspension or replacement with a biological or mechanical valved conduit. When HCA times were greater than 50 minutes, antegrade cerebral perfusion is used. Since Februay 1999, BioGlue has been used as an anastomotic adjunct in the repair of type A dissections., Results: Mean age was 62 +/- 14 years, with 68% men and 15% with previous cardiac surgery. Seven percent of patients presented with a preoperative neurologic deficit, and 3% developed a new cerebrovascular accident after dissection repair. The in-hospital death rate was 9.8%. Excluding the patients with preoperative strokes (7%) and those with postoperative stroke (3%), the in-hospital death rate was 6.6%. In 6 patients, prompt changes in circulatory management consisting of switching cannulation sites or cross-clamp release with direct temporary aortic arch fenestration occurred when there were sudden changes in electroencephalogram during cooling., Conclusions: A standardized approach to the treatment of acute type A dissections has improved outcomes. Our 55% mortality in patients with preoperative cerebral vascular accident (CVA) suggests that this group may be candidates for medical or delayed surgical treatment. Conversely, our 6.6% mortality rate for neurologically intact patients warrants aggressive and expeditious surgical intervention.

Background: Left ventricular remodeling secondary to acute myocardial infarction (AMI) is characterized by ventricular dilatation and regional akinesis. In this study, we investigated the effect of passive constraint on akinetic area development., Methods and Results: The effect of passive constraint on akinetic area was investigated in 10 sheep using tissue-tagging magnetic resonance imaging (MRI). A baseline MRI study was followed by the creation of an anterior infarct. After 1 week, the animals received a second MRI study. A cardiac support device (CSD) was then placed over the epicardium in 5 sheep whereas the remaining animals served as controls. A terminal study was performed at the 2-month postinfarct in both groups. The akinetic area at 1-week postinfarct was similar in both groups. At the terminal time-point, the akinetic area in the control group was similar to the 1-week time-point whereas in the CSD group, the area of akinesis decreased (P=0.001). A comparison of the 2 groups at the terminal time-point demonstrates a significantly diminished area of akinesis in the CSD group (P=0.004). The relative area of akinesis followed a similar pattern. End-systolic and end-diastolic wall thickness was significantly greater in the CSD group at terminal (P=0.001). In addition, the minimum wall thickness was greater in the CSD group compared with the controls (P=0.04)., Conclusions: Passive constraint reduced akinetic area development secondary to AMI. The attenuation of regional wall stress may prevent the incorporation of the border zone into the infarct, decreasing infarct size and providing a promising new therapy for patients after an AMI.

This study tests the hypothesis that hypocontractile, borderzone myocardium adjacent to an expanding infarct becomes progressively larger and more hypocontractile as remodeling continues. Early infarct expansion following anteroapical myocardial infarction (MI) is associated with progressive ventricular dilation and heart failure. The contribution of perfused, hypocontractile, borderzone myocardium to this process is unknown. Using a sheep model of anteroapical infarction, sonomicrometry array localization and serial microsphere injections were used to track changes in regional myocardial contractility, geometry, and perfusion. Eight sheep were studied before and after infarction and two, five, and eight weeks later. Thirty intertransducer chord lengths were analyzed to measure regional contractility and serial changes in regional geometry at end systole. Beginning as a narrow band of fully perfused hypocontractile myocardium adjacent to the infarction, borderzone myocardium extends to involve additional contiguous myocardium that progressively loses contractile function as the heart remodels. Three distinct myocardial zones develop as a result of transmural MI: infarct, borderzone (perfused but hypocontractile), and remote (perfused and normally functioning).This study demonstrates that hypocontractile, fully perfused borderzone myocardium extends to involve contiguous normal myocardium during postinfarction remodeling. This borderzone myocardium is a unique type of perfused, hypocontractile myocardium, which is distinct from hibernating or stunned myocardium. Preventing extension of borderzone myocardium by medical or surgical means offers the prospect of preventing late-onset heart failure following transmural expanding MIs.

Right (systemic) ventricular dysfunction is well described after Senning operations for transposition of the great arteries, and patients with congenitally corrected transposition of the great arteries. Transplantation remains the only definitive therapy for refractory heart failure, however patients may deteriorate clinically prior to the availability of a donor heart. This report details the implantation of a TCI Heartmate (Thoratec Corp., Pleaston, CA) as a morphologic right ventricular assist device to bridge these patients to transplantation.

Background: Coronary arterial disease is the major cause of congestive heart failure, but suitable animal models of postinfarction, dilated cardiomyopathy do not exist. This article describes an ovine model that develops after an anterobasal infarction., Methods: The distribution of ovine myocardium supplied by the first two diagonal branches of the left homonymous artery were determined in 20 slaughterhouse hearts and eight live sheep using methylene blue and tetrazolium injections, respectively. Seven additional animals had the infarction and underwent serial hemodynamic, microsphere and echocardiographic studies more than 8 weeks and histologic studies at the eighth week. Infarcts represented 24.6% +/- 4.7% and 23.9% +/- 2.2% of the left ventricular mass in slaughterhouse and live hearts, respectively., Results: During remodeling, left ventricular end-systolic and end-diastolic volumes increased 115% and 73%, respectively, ejection fraction decreased from 41.2% +/- 6.7% to 29.1% +/- 5.7%, systolic wall thickening remote from the infarct decreased by 68%, sphericity index increased from 0.465 +/- 0.088 to 0.524 +/- 0.038, and left ventricular end-diastolic pressure increased from 1.7 +/- 1.0 to 8.2 +/- 3.5 mm Hg. Serial microsphere measurements documented normal blood flow (1.34 mL/g per minute) to all uninfarcted myocardium and 22% of normal to the infarct. Viable myocardium showed mild interstitial fibrosis., Conclusions: This ovine model meets all criteria for postinfarction, dilated cardiomyopathy and has the advantages of controlling for variations in coronary arterial anatomy, collateral vascularity, and differences in the numbers, location, and severity of atherosclerotic lesions that confound human studies of the pathogenesis of this disease. This simple model contains only infarcted and fully perfused, hypocontractile myocardium produced by a moderate-sized, regional infarction.

Background: Leaflet curvature is known to reduce mechanical stress. There are 2 major components that contribute to this curvature. Leaflet billowing introduces the most obvious form of leaflet curvature. The saddle shape of the mitral annulus imparts a more subtle form of leaflet curvature. This study explores the relative contributions of leaflet billowing and annular shape on leaflet curvature and stress distribution., Methods and Results: Both numerical simulation and experimental data were used. The simulation consisted of an array of numerically generated mitral annular phantoms encompassing flat to markedly saddle-shaped annular heights. Highest peak leaflet stresses occurred for the flat annulus. As saddle height increased, peak stresses decreased. The minimum peak leaflet stress occurred at an annular height to commissural width ratio of 15% to 25%. The second phase involved data acquisition for the annulus from 3 humans by 3D echocardiography, 3 sheep by sonomicrometry array localization, 2 sheep by 3D echocardiography, and 2 baboons by 3D echocardiography. All 3 species imaged had annuli of a similar shape, with an annular height to commissural width ratio of 10% to 15%., Conclusion: The saddle shape of the mitral annulus confers a mechanical advantage to the leaflets by adding curvature. This may be valuable when leaflet curvature becomes reduced due to diminished leaflet billowing caused by annular dilatation. The fact that the saddle shape is conserved across mammalian species provides indirect evidence of the advantages it confers. This analysis of mitral annular contour may prove applicable in developing the next generation of mitral annular prostheses.

Background: Chronic ischemic mitral regurgitation (IMR) is produced by adverse postinfarction ventricular remodeling. We hypothesize that restraining infarct expansion reduces left-ventricular (LV) dilatation and the severity of mitral regurgitation., Methods: Two groups of 6 sheep had coronary snares placed around the second and third obtuse marginal coronary arteries and four piezoelectric transducers sutured within myocardium across the mid short axis of the LV. In one group, a patch of Marlex mesh was precisely fitted and lightly sutured to myocardium destined for infarction (determined by temporary snare occlusion). Two weeks after instrumentation, coronary snares were tied tight to infarct approximately 24% of the posterolateral LV mass. Transdiaphragmatic echocardiograms were obtained in all animals at baseline, and 30 minutes, and 2, 5, and 8 weeks after infarction., Results: Echocardiograms confirmed similar infarct sizes and locations in both groups. Eight weeks after infarction, IMR grade averaged 3.6+ (scale: 0, no MR; 4, severe MR) in control sheep and 1.9+ in mesh-restrained animals (p = 0.0001). LV end-diastolic and end-systolic volumes at the eighth week were less in mesh-treated sheep (87 +/- 11.3 vs 113 +/- 18.3; 61 +/- 10.6 vs 77 +/- 14.1, respectively), but differences were not significant. Data from mid short axis piezoelectric transducers indicated significantly less strain in the infarcted myocardium in mesh-restrained sheep than in control., Conclusions: Early restraint of postero-lateral infarct expansion attenuates the severity of ischemic mitral regurgitation and slows ventricular dilatation. However, the remodeling process is not arrested 8 weeks after infarction.