Cardiovascular Pathology

Histological correlate of a cardiac magnetic resonance imaged microvascular obstruction in a porcine model of ischemia–reperfusion

2011-09-23

Abstract: Background: Microvascular obstruction after reperfusion therapy of acute myocardial infarction is reported as an adverse promoter of left ventricular remodeling and is an important target to prevent deterioration into heart failure. In this study, we illustrate the early onset of a magnetic resonance imaged microvascular obstruction in a porcine model of acute myocardial infarction with the exact histological correlate.Methods: Occlusion of the left anterior descending coronary artery followed by 3-h reperfusion was performed in 10 pigs. Microvascular obstruction was assessed by contrast-enhanced magnetic resonance imaging (MRI). After sacrifice, serial sectioned slices of the hearts matching the MRI were stained with Triphenyl tetrazolium chloride (TTC). Biopsies were fixed, embedded in paraffin, and stained for hematoxylin–eosin.Results: Microvascular obstruction was defined with MRI as a hypoenhanced no-reflow area within the hyperenhanced infarct region. Erythrocyte plugging was consistently observed in the no-reflow area and was completely absent in the adjacent hyperenhanced infarct region.Conclusion: This model of acute ischemia–reperfusion contributes to the histological comprehension of contrast-enhanced MRI during the early stages of myocardial infarction.

Granulation tissue is altered after intramyocardial and intracoronary bone marrow-derived cell transfer for experimental acute myocardial infarction

2011-08-12

Abstract: Background: Bone marrow-derived mononuclear cell (BMMC) treatment in acute myocardial infarction (AMI) has been shown to have a beneficial effect. Our objective was to study in detail the histopathological process after the cell therapy after intramyocardial (IM) or intracoronary (IC) administration of BMMCs following experimental AMI.Methods: Twenty-fours pigs were randomized to the IM group (n=8), the IC group (n=8), and the control group (n=8).After 90 min of transient occlusion of the circumflex coronary artery, BMMCs were injected either intramyocardially or by a transfemoral catheter into the circumflex coronary artery. Echocardiography was performed preoperatively, postoperatively, and after a 21-day recovery period. The heart biopsies were examined histopathologically. Volumetric ex vivo CT scan was performed to evaluate calcification of the infarcted myocardium.Results: The ejection fraction (EF) showed significant recovery in the IM group compared to the control group at Day 21 (P=.05). Despite beneficial histological changes in the infarction site in the IC group, compared to the control group, EF failed to recover. Reduction of collagen density that depicts scar formation was seen in both cell therapy groups compared to the control (P<.001). The number of mitotic cells was higher in the control group compared to the cell therapy groups (P<.001). The IC and IM groups differed significantly from each other in muscle-specific actin staining (P<.001) and smooth muscle actin staining (P<.004). The IM therapy group showed higher density for both stainings. Additionally, macrophage density was higher in the IC group compared to the IM and control groups (P<.002). Both cell therapy regimens substantially diminished tissue calcification; due to the large variation, the effect was not statistically significant.Conclusion: BMMC therapy launches cellular changes that affect mostly the repair process in the granulation tissue. The cell transplantation method might have some effect on the magnitude of the effect.

Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits

2011-10-17

Abstract: Introduction: Myocardial infarction (MI) results in cardiac nerve sprouting in the myocardium. Whether or not similar neural remodeling occurs in the stellate ganglia (SGs) is unknown. We aimed to test the hypothesis that MI induces bilateral SG nerve sprouting.Methods: Acute MI was created by coronary artery ligation in rabbits (n=12). Serum nerve growth factor (NGF) level was measured by enzyme-linked immunosorbent assay. The hearts and bilateral SGs were harvested for immunohistochemistry after 1 week in six rabbits and after 1 month in six rabbits. Immunostaining for tyrosine hydroxylase (TH), growth-associated protein 43 (GAP43), choline acetyltransferase (ChAT), and synaptophysin (SYN) was performed to determine the magnitude of nerve sprouting. Tissues from six normal rabbits were used as controls. Nerve density was determined by computerized morphometry.Results: Myocardial infarction results in increased serum NGF levels at 1 week (1519.8±632.2 ng/ml) that persist up to 1 month (1361.2±176.3 ng/ml) as compared to controls (89.6±34.9 ng/ml) (P=.0002 and P=.0001, respectively). Immunostaining demonstrated nerve sprouting and hyperinnervation in both SGs after MI. The nerve densities (μm2/ganglion cell) in SG 1 week after MI and 1 month after MI and those in control groups, respectively, were as follows: GAP43: 278±96, 225±39, and 149±57 (P=.01); SYN: 244±152, 268±115, and 102±60 (P=.02); TH: 233±71, 180±50, and 135±68 (P=.047); ChAT: 244±100, 208±46, and 130±41 μm2/cell (P=.01).Conclusions: Myocardial infarction increases serum NGF levels and induces nerve sprouting and hyperinnervation in bilateral SGs for at least 1 month after MI. The hyperinnervation includes both adrenergic axons and cholinergic axons in the SG.

Degeneration of sensory afferent nerves enhances pulmonary inflammatory alterations in acute myocardial infarction in rats

Jie Wu, Zheng Guo, Li-Li Wang, Rui-Lin Zhang — 2011-06-13

Abstract: Background: Evidence suggests proinflammatory changes in the lungs during acute myocardial infarction and a participation of neural mechanisms and substance P in the pathology. This study was undertaken to investigate the role and the mechanisms by which sensory afferent degeneration at neonatal stages exacerbates the pulmonary inflammatory responses to acute myocardial infarction in the adult rats.Methods: The degeneration of capsaicin-sensitive afferent nerves was induced by administration of capsaicin to neonatal rats. The pulmonary inflammatory changes following coronary artery occlusion (CAO) were assessed by the analysis of the infiltration of neutrophils and tissue morphology in the lungs.Results: Significant increases in the pulmonary infiltration of neutrophils, up to 240% and 218% of the sham controls at 3 and 6 h, respectively, after CAO (P<.05) and marked pulmonary edema were observed. Degeneration of capsaicin-sensitive afferent nerves or antagonism of endogenous neurokinin (NK)-1 receptor exacerbated the pulmonary infiltration of neutrophils (up to 214% and 254% of the controls, respectively) and pulmonary tissue edema following the CAO.Conclusion: The findings indicate that degeneration of sensory afferent nerves enhances the pulmonary inflammatory changes in acute myocardial infarction, in which the endogenous NK may play a role.

Characterizing the inflammatory reaction in explanted Medtronic Freestyle stentless porcine aortic bioprosthesis over a 6-year period

2011-08-04

Abstract: Background: The Medtronic Freestyle valve is a stentless porcine valve with reportedly excellent clinical and hemodynamic results, but little has been reported about its long-term pathology.Methods: Seventeen Freestyle valves were explanted (from 2003 to 2009) and reviewed to assess reasons for bioprosthesis failure. All valves were examined in detail, using histochemistry and immunohistochemistry to identify morphological changes, as well as cellular and humoral responses.Results: One Freestyle valve, explanted for mitral valve endocarditis on the fifth postoperative day, was excluded from analysis. The average implant duration was 71.1±35.2 months. Six valves were explanted for infective endocarditis, six for aortic insufficiency, and four for aortic stenosis. Calcification was seen in 11 explants, pannus in 15, thrombus in 12, cusp tears in 9, and 10 explants showed needle tract-like injuries. A chronic inflammatory reaction involving the xenograft arterial wall was seen in 15 of 16 valves. The cells were composed of macrophages and lymphocytes, including T cells (CD8 positive) and B cells. Significant damage to the porcine aortic wall was seen in 15 cases, and cusp myocardial shelf damage in 7 cases. All cases stained positively for IgG and C4dpar.Conclusions: The porcine aortic tissue showed T cell-mediated rejection and significant aortic medial damage, consistent with dilatation of the porcine aortic root. The demonstration of IgG suggests the likelihood of humoral rejection, in addition to cellular rejection. One of the underlying possibilities is that the porcine aortic tissues are inadequately fixed, hence the retained antigenicity.

Juxtaposition of the atrial appendages

Carla Frescura, Gaetano Thiene — 2011-04-13

Abstract: Juxtaposition of the atrial appendages is a rare congenital cardiac malformation, with the appendages both located on the left or right side of the great arteries. It is usually associated with cyanotic congenital heart disease.The aim of this report is to illustrate the anatomical features of normal and juxtaposed atrial appendages, with a review of the associated anomalies.In the Anatomical Collection of Congenital Heart Disease of the University of Padua, consisting in 1,526 specimens, we found 17 (1.1%) cases of atrial appendages juxtaposition with left juxtaposition in 15 (88%) and right juxtaposition in 2 (12%). Complete form was present in 11 cases and partial form in 6.In left juxtaposition, the situs was solitus in all, and the most frequent anomalies were complete transposition of great arteries in 9 (60%) and tricuspid atresia in 5 (33%); anomalies of position of the heart in the thorax (dextro-mesocardia) were present in 46% of cases, hypoplastic right ventricle in 73%, abnormal relation of the great arteries and subaortic or bilateral infundibulum in all.In right atrial juxtaposition, the atrial situs was solitus with mitral and pulmonary atresia in one case and left isomerism with aortic atresia and double-inlet right ventricle in the other.In describing this malformation, we propose to maintain the use of a positional definition using the terms right and left juxtaposition to describe the presence of both the appendages on the right or on the left side of the great arteries, respectively. The use of a morphological definition should be added in cases of situs inversus or isomerism, with description of the morphology of the appendage located in the wrong position.

Atypical cardiac myxomas: a clinicopathologic analysis and their comparison to 64 typical myxomas

Pradeep Vaideeswar, Rajib Gupta, Prashant Mishra, Charan Lanjewar, Abhijit Raut — 2011-08-12

Abstract: Introduction: Myxomas are the most common among the primary cardiac neoplasms, seen mainly in adult population, and are typically attached to the interatrial septum, on the left side. Myxomas arising from other sites are designated as “atypical myxomas.” In this article, we describe the clinicopathologic features of 28 such lesions, resected in 20 patients.Methods: A 15-year study (1995–2009) of all cardiac myxomas, received as surgical excisions in our institution, was performed. Atypical myxomas were selected on the basis of their atypical sites of origin, and a systematic review and comparison of their clinicopathologic features with all typical myxomas excised during the same period were done.Results: Among a total of 84 patients who had undergone cardiac myxoma excisions in this 15-year duration, 64 patients had typical myxomas, while atypical myxomas (30 tumors) were diagnosed in 20 patients (23.8%). None of them had a family history of similar symptoms. There were six children. In the atypical subset, there were 12 males and eight females; the mean age of diagnosis was 33.7 years. This demography differed from the typical myxoma group where there were more females than males and the mean age of diagnosis being 40.8 years. The symptoms of dyspnea, episodic chest pain, and palpitation were common in both cohorts of patients, and all showed a mass lesion with varying degrees of valvular regurgitation and obstruction on echocardiography. Five of the 20 patients with atypical myxomas had multifocal or multicentric tumors. Grossly, like typical myxomas, the atypical ones also exhibited solid and papillary patterns with the usual histological features. Four patients had recurrence of the disease.Conclusions: Atypical myxomas are rare lesions having clinical and pathological features, not entirely different from those of typical myxomas. With the advent of modern diagnostics, it is now imperative to do genetic studies and screen the relatives of patients having atypical myxomas to rule out additional occult familial cases as they are now known to occur more in this “atypical” group.

Variable phenotype in murine transverse aortic constriction

2011-07-18

Abstract: Background: In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload-induced hypertrophy (left ventricular [LV] hypertrophy, or LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, noninvasive method of prospectively identifying mice with HF versus compensated LVH after TAC.Methods: Eight-week-old male C57BL/6J mice underwent TAC or sham and then echocardiography at 3 weeks post-TAC. A group of sham and TAC mice were euthanized after the 3-week echocardiogram, while the remainder underwent repeat echocardiography and were euthanized at 9 weeks post-TAC. The presence of TAC was assessed with two-dimensional echocardiography, anatomic aortic m-mode and color flow, and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset of mice. HF was defined as lung/body weight>upper limit in sham-operated mice.Results: As compared with sham, TAC mice had higher TA velocity, LVP and LV weight, and lower ejection fraction (EF) at 3 or 9 weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared with compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening, and more fibrosis. Both EF and LV mass measured by echocardiography at 3 weeks post-TAC were predictive of the presence of HF at 3 or 9 weeks post-TAC.Conclusions: In wild-type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echocardiography 3 weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies.

Age is a risk factor for maladaptive changes of the pulmonary root in rats exposed to increased pressure loading

2011-08-18

Abstract: Introduction: Pulmonary artery root does not adapt properly when exposed to increased pressure stress, with progressive dilatation. The aim of this study was to evaluate, in an animal model, the histologic changes of the pulmonary root wall under increased pressure load.Methods and Results: To increase the systolic pressure in the pulmonary root, a banding of the pulmonary artery (PAB) was performed in 10 adult Sprague–Dawley rats and in 10 weanlings, using 7 adults and 8 weanlings as controls. We analyzed the structural changes of the pulmonary artery root after 30 days of increased pressure load.The mean pressure gradient across the banded pulmonary trunk was 53.57 ± 10 mmHg in the adult rats and 86.73 ± 15 mmHg in the weanlings. The pulmonary artery wall was significantly thicker in both age groups of PAB rats when compared to age-matched controls, showing also architectural structural changes, as a higher degree of mucoid degeneration, medionecrosis, and fibrosis as well as elastic fibers fragmentation. The apoptotic index was also increased in both PAB age groups. We also confirmed the physiologic higher degree of elastic fibers disarray in adult rats when compared to weanlings.Conclusions: The pulmonary artery wall seems to present maladaptive architectural changes in the media when exposed to systemic pressure. The PAB-related increase of the apoptotic index seems to reflect an accelerated involution of the pulmonary root's media. The physiologic higher degree of elastic fibers disarray in adult rats can possibly influence the worst adaptation of the pulmonary arterial wall to a systemic pressure load.

Elevated cyclic stretch and serotonin result in altered aortic valve remodeling via a mechanosensitive 5-HT2A receptor-dependent pathway

2011-08-24

Abstract: Introduction: Serotonin/5-hydroxytryptamine (5-HT) has been implicated in valve disease and in the modulation of valve mechanical properties. Several 5-HT receptor subtypes are also known to be mechanosensitive in other cell types, but this has not been studied in the context of the valve. In this study, we sought to understand the effects of elevated 5-HT levels and stretch overload on aortic valve remodeling and the dominant 5-HT receptor subtype that regulates these processes.Methods and results: Collagen biosynthesis and tissue mechanical properties of porcine aortic valve cusps were evaluated after 10% (physiologic) and 15% (pathologic) dynamic stretch. These studies were performed in normal medium or medium supplemented with 5-HT (1, 10, 100 μM) in the absence and presence of 5-HT2A or 5-HT2B receptor antagonists. Fresh valves served as controls. Valve collagen content was maximal at the 10-μM 5-HT concentration for both 10% and 15% stretch. The 5-HT2A receptor antagonist reduced collagen synthesis, cell proliferation, and hsp47 expression under elevated and normal stretch, whereas the 5-HT2B receptor antagonist was effective only at normal stretch. The pretransition stiffness of the valve cusps was also increased in response to 5-HT via a stretch-sensitive 5-HT2A mechanism, with the post-transition stiffness unaltered.Conclusions: Combined elevated stretch and 5-HT resulted in increased valve collagen biosynthesis, cell proliferation, and tissue stiffness. These responses were inhibited by a 5-HT2A antagonist. This strongly suggests that the 5-HT2A receptor subtype is sensitive to elevated stretch.

Deletion of discoidin domain receptor 2 does not affect smooth muscle cell adhesion, migration, or proliferation in response to type I collagen

Guangpei Hou, David Wang, Michelle P. Bendeck — 2011-08-24

Abstract: Collagen receptors expressed on vascular smooth muscle cells include the discoidin domain receptors (DDR1 and DDR2). DDR1 is known to play important roles in mediating smooth muscle cell responses to vascular injury, including neointimal hyperplasia, but much less is known about the function of DDR2. In this study, we harvested smooth muscle cells from DDR2 wild-type and knockout mice and studied the cells using in vitro models of migration and growth. There were no significant differences in the ability of Ddr2+/+ or Ddr2−/− smooth muscle cells to attach to, migrate, or proliferate on type I collagen. Furthermore, neither matrix metalloproteinase (MMP) 2 nor MMP-9 activity nor type I collagen expression was different between the cell types. We conclude that in vitro, endogenous DDR2 is not required for smooth muscle cell hyperplastic responses to collagen.

Development of a mathematical model to describe the transport of monocyte chemoattractant protein-1 through a three-dimensional collagen matrix

Krisada Leemasawatdigul, Heather Gappa-Fahlenkamp — 2011-11-21

Abstract: Introduction: Monocyte chemoattractant protein-1 is a bioactive molecule that is expressed in significant amounts in all stages of atherosclerosis. The role of monocyte chemoattractant protein-1 in this disease is to recruit monocytes across the endothelium and into the arterial tissue. Eventually, the monocytes differentiate into cholesterol-engorged macrophages called “foam cells” that result in atherosclerotic plaque formation. The mechanism that monocyte chemoattractant protein-1 uses to mediate monocyte transendothelial migration is believed to be via its concentration gradient. However, the formation of the monocyte chemoattractant protein-1 concentration gradient in the extracellular matrix is still poorly understood.Methods: A three-dimensional in vitro vascular tissue model has been developed to study the cellular mechanisms involved in the early stages of atherosclerosis. In the present study, a mathematical model is used to determine the gradient of monocyte chemoattractant protein-1 in the collagen matrix of the three-dimensional in vitro vascular tissue model. Experiments were performed to investigate the stability of monocyte chemoattractant protein-1 and the interaction between monocyte chemoattractant protein-1 and the collagen matrix.Results and conclusions: Monocyte chemoattractant protein-1 is stable for at least 24 h under experimental conditions and monocyte chemoattractant protein-1 interacts with the collagen matrix. The diffusion coefficient for the transport of monocyte chemoattractant protein-1 in the collagen matrix and the rate constant for the binding of monocyte chemoattractant protein-1 to collagen were determined to be 0.108 mm2 h−1 and 0.858 h−1, respectively. Numerical results from the model indicate that the concentration gradients of both soluble and matrix-bound (or static) monocyte chemoattractant protein-1 are formed inside the collagen matrix.

Onchocerca armillata contamination of a bovine pericardial xenograft in a human patient with repaired tetralogy of Fallot

Cheryl Mather, Piper Treuting — 2011-08-10

Abstract: Background: Bovine pericardial patches are used for many purposes, including facilitating right ventricular outflow tract reconstruction in patients with congenital heart disease. Here we present a case of parasitic contamination of a bovine pericardium used as a transannular patch during repair of tetralogy of Fallot 28 years prior at a hospital in China.Methods: The patient presented to the University of Washington Medical Center for congestive heart failure and pulmonic regurgitation, and heart tissues including the xenograft pericardial patch were submitted to the Pathology Department and subsequently to the Comparative Pathology Program.Results: The pericardial parasitic nodules with intralesional adult nematodes and microfilaria in the bovine tissues were preserved at harvest by (presumed) glutaraldehyde fixation.Conclusion: Onchocerca armillata parasitic pericardiopathy was diagnosed in the xenograft tissue based on the characteristic nematode morphology and the presumed geographic location of the donor bovine. This resulted in O. armillata contamination of the pericardial xenograft in a human patient with repaired tetralogy of Fallot.

Congenital left main coronary artery aneurysm

Roberto Andrés Guerri-Guttenberg, Gabriela Celeste Francos, José Milei — 2011-08-01

Abstract: We report a rare case of a congenital left main coronary artery aneurysm in a 2-year-old patient with concomitant intimal hyperplasia and strong intimal apolipoprotein B expression.

Editorial Board

2012-05-01