Cardiovascular Pathology

Looking forward for Cardiovascular Pathology

L. Maximilian Buja — 2012-01-01

I am honored to have been selected by the leadership of the Society for Cardiovascular Pathology to be the new Editor-in-Chief of Cardiovascular Pathology for a 5-year term beginning with this issue of the journal. I am enthusiastic about the opportunity to build on the pioneering effort of the founding editor, Dr. Stephen Factor, and the excellent work of Dr. Jagdish Butany and Dr. Avrum Gotlieb, who have served as Editors-in-Chief for the last 10 years. I am being joined in the stewardship of the journal by a reconstituted Editorial Board composed of a multidisciplinary group of experts and scholars in the areas of cardiovascular pathology, vascular and myocardial biology, and cardiovascular medicine and surgery.

Recommendations for processing cardiovascular surgical pathology specimens: a consensus statement from the Standards and Definitions Committee of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology

2011-02-25

Abstract: With the advent of molecular subclassification of diseases, much consideration should be given to the proper processing of cardiovascular surgical pathology specimens to maximize patient care. Such specimens include endomyocardial biopsies, cardiac myectomy specimens, cardiac apical core segments, resected cardiac valves, pericardial biopsies, resected segments of aorta, cardiac tumors, vascular stents, vascular grafts, cardiac devices, resected veins, arterial biopsies including temporal artery biopsies and hearts removed during cardiac transplantation. In this report, the Standards and Definitions Committee of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology present consensus guidelines for the gross description, sectioning, processing, and staining of these specimens. This report is presented to aid pathologists, pathology assistants, and clinicians in maximizing the diagnostic utility of cardiovascular surgical pathology specimens for enhanced patient care.

Insulin-like growth factor-1 overexpression in cardiomyocytes diminishes ex vivo heart functional recovery after acute ischemia

2011-01-27

Abstract: Background: Acute insulin-like growth factor-1 administration has been shown to have beneficial effects in cardiac pathological conditions. The aim of the present study was to assess the structural and ex vivo functional impacts of long-term cardiomyocyte-specific insulin-like growth factor-1 overexpression in hearts of transgenic αMHC-IGF-1 Ea mice.Methods: Performance of isolated transgenic αMHC-IGF-1 Ea and littermate wild-type control hearts was compared under baseline conditions and in response to 20-min ischemic insult. Cardiac desmin and laminin expression patterns were determined histologically, and myocardial hydroxyproline was measured to assess collagen content.Results: Overexpression of insulin-like growth factor-1 did not modify expression patterns of desmin or laminin but was associated with a pronounced increase (∼30%) in cardiac collagen content (from ∼3.7 to 4.8 μg/mg). Baseline myocardial contractile function and coronary flow were unaltered by insulin-like growth factor-1 overexpression. In contrast to prior evidence of acute cardiac protection, insulin-like growth factor-1 overexpression was associated with significant impairment of acute functional response to ischemia–reperfusion. Insulin-like growth factor-1 overexpression did not modify ischemic contracture development, but postischemic diastolic dysfunction was aggravated (51±5 vs. 22±6 mmHg in nontransgenic littermates). Compared with wild-type control, recovery of pressure development and relaxation indices relative to baseline performance were significantly reduced in transgenic αMHC-IGF-1 Ea after 60-min reperfusion (34±7% vs. 62±7% recovery of +dP/dt; 35±11% vs. 57±8% recovery of −dP/dt).Conclusions: Chronic insulin-like growth factor-1 overexpression is associated with reduced functional recovery after acute ischemic insult. Collagen deposition is elevated in transgenic αMHC-IGF-1 Ea hearts, but there is no change in expression of the myocardial structural proteins desmin and laminin. These findings suggest that sustained cardiac elevation of insulin-like growth factor-1 may not be beneficial in the setting of an acute ischemic insult.

Proteinase inhibitor 9 is reduced in human atherosclerotic lesion development

2011-02-08

Abstract: Background: Granzyme B, a proapoptotic serine protease, is abundant in advanced, unstable atherosclerotic plaques, and it is suggested to contribute to plaque instability by inducing vascular smooth muscle cells apoptosis and by degrading plaque extracellular matrix. Proteinase inhibitor 9, the only known endogenous inhibitor of granzyme B in humans, confers protection against granzyme-B-induced apoptosis. However, the role of proteinase inhibitor 9 in atherosclerotic lesion development has yet to be determined. We hypothesized that atherosclerotic lesions have lower proteinase inhibitor 9 expression levels that will increase their susceptibility to granzyme-B-induced apoptosis.Methods: Serial sections of human coronary arteries exhibiting different stages of lesion development were assessed by immunohistochemistry for proteinase inhibitor 9, α-smooth muscle cells actin, granzyme B, CD8, and active caspase-3. Frozen samples were analyzed by Western blot to evaluate total proteinase inhibitor 9 levels.Results: Vascular smooth muscle cells express less proteinase inhibitor 9 as disease severity increases, and a significant difference in proteinase inhibitor 9 expression is observed between medial and intimal smooth muscle cells. High granzyme B levels colocalize with CD8+ cells and foam cells in the shoulder region and necrotic core area of advanced lesions. In advanced lesions, increased expression of activated caspase-3 in intimal SMC was associated with reduced proteinase inhibitor 9 expression in the presence of granzyme B.Conclusion: Reduced proteinase inhibitor 9 expression in human vascular smooth muscle cells is associated with atherosclerotic disease progression and is inversely related to the extent of apoptosis within the intima. Reduced proteinase inhibitor 9 expression may contribute to increased smooth muscle cell susceptibility to granzyme-B-induced apoptosis within the plaque.

Parasympathetic and substance P-immunoreactive nerve denervation in atrial fibrillation models

Yang Yu, Li Liu, Jiu Yang Jiang, Xiu Fen Qu, Guang Yu — 2011-02-25

Abstract: Background: Recent studies demonstrated that atrial fibrillation (AF) induced heterogeneous sympathetic hyperinnervation and baroreflex impartation, but the changes of vagal and afferent nerve are not clear.Methods: Six dogs underwent atrial pacing at 600 beats/min (AF group). All paced dogs developed sustained AF by 5 weeks of pacing. Tissues from six healthy dogs were used as controls. Immunohistochemistry staining of cardiac nerves was performed using anti-growth-associated protein 43 (anti-GAP43), anti-tyrosine hydroxylase, antiacetylcholine (anti-ACh), and anti-substance P (anti-SP) antibodies.Results: In AF group, the density of GAP43-positive in the right atrium (RA), atrial septum (AS), and left atrium (LA) was 5590.24±1417.51, 8083.22±1271.39, and 10854.56±1877.56 μm2/mm2, respectively, which was significantly (P<.01) higher than the control group. Most of the newly sprouting nerves are sympathetic nerve. Sympathetic nerve density in AF group was significantly higher than that of control group (P<.001). Whereas denervation of parasympathetic and SP-immunoreactive nerve occurred in AF group. In the dogs with AF, the density of ACh-positive nerve in the RA, AS, and LA was 506.04±104.44, 317.72±84.10, and 114.9±29. 62 μm2/mm2, respectively, which was lower than the control group (P<.01). At the same time, the density of SP-positive nerve in the atria of AF dogs was also significantly lower than the control tissues (P<.01).Conclusion: AF led to significant nerve sprouting and sympathetic hyperinnervation in the canine models, but the newly sprouting nerve did not include parasympathetic and SP-immunoreactive nerve. Heterogeneous parasympathetic and SP-immunoreactive nerve denervation occurred in the AF dogs.

Insight into pathologic abnormalities in congenital semilunar valve disease based on advances in understanding normal valve microstructure and extracellular matrix

Elizabeth H. Stephens, Debra L. Kearney, K. Jane Grande-Allen — 2011-02-24

Abstract: Congenitally diseased valves are relatively frequent causes of significant morbidity and mortality. Pathology descriptions of such valves have primarily focused on gross structural features including the number of leaflets or commissures (bicuspid/bicommissural valve) and alterations in the contour, thickness, and consistency of the leaflets (dysplastic valve). Functional correlates of these pathologic alterations are valvar stenosis, insufficiency, or both. Further characterization of the microstructural abnormalities seen in these malformed valves may not only provide insight into the correlation of distinct pathologies with their respective pathogenesis and clinical sequelae but also prove pivotal in uncovering new avenues for therapeutic interventions and prevention regimens. This review summarizes microstructural findings in congenital semilunar valve disease (CSVD) and discusses their relevance in light of recent advances in knowledge of normal valve microstructure, biology, and function. Specifically, the biological and mechanical roles of various matrix components and their interactions are discussed in the context of CSVD. Indeed, recent research in normal valves adds significant insight into CSVD and raises many hypotheses that will need to be addressed by future studies.

Autopsy demonstration of intramyocardial polymer gel emboli associated with a giant-cell reaction following cardiac catheterization: a case report

Vicky El-Najjar, Morton Robinson — 2011-07-08

Abstract: Background: Foreign body type granulomatous vasculitis has been reported in blood vessels of the brain, lungs, and skin of the foot following intravascular instrumentation with devices coated with hydrophilic polymer gel. We report a case of intramyocardial polymer gel emboli associated with granulomatous vasculitis following cardiac catheterization.Method: Autopsy observations in a 77-year-old woman are presented. The patient experienced an acute myocardial infarction requiring catheterization and coronary stenting. The patient returned with a pseudoaneurysm at the site of catheterization and shortly after suffered a fatal arrhythmia.Results: Microscopically, multiple small vessels within the myocardium were noted to contain a basophilic, amorphous, focally lamellated, focally granular material. A granulomatous inflammatory response was noted in the vessels containing the foreign material.Conclusions: Our case is the first to our knowledge to document intramyocardial vessel gel emboli following a cardiac catheterization with stenting. Although the microscopic finding of emboli within vessels does not seem to be the immediate cause of death in our case, it is highly possible that it contributed to the patient's demise.

In memoriam: Jack L. Titus, M.D., Ph.D., 1926–2011

Frederick J. Schoen — 2011-10-17

Jack L. Titus, M.D., Ph.D., passed away in North Oaks, MN, after a long illness on June 15, 2011, at the age of 84 (). I will miss Jack as a friend and as a highly respected colleague and collaborator, who had a long and distinguished career. He was for me the ideal mentor at an extremely pivotal stage of my career, and we continued to be close, sharing many professional and other interests as my career continued to develop. He trained and collaborated with numerous other cardiovascular pathologists, many of whom themselves have made important contributions to the field. I and the many others he touched have lost an important leader in academic medicine and pathology, nationally and internationally, and a giant in the world of cardiovascular pathology.

Editorial Board

2012-01-01