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M B Gravanis

Publications and source records attributed to M B Gravanis.

At least 19 recordsLinked to original sources
PubMed1992

Coronary intimal proliferation after balloon injury and stenting in swine: an animal model of restenosis.

OBJECTIVES: This study was designed to compare the proliferative response in coronary arteries after tantalum stent placement or balloon injury in a normolipemic swine model of restenosis. BACKGROUND: Restenosis remains a significant complication of percutaneous transluminal coronary angioplasty. Efforts to study restenosis have been hampered by the lack of a suitable animal model. METHODS: In an attempt to create lesions resembling those of human restenosis, normolipemic swine underwent injury of either the left anterior descending or the left circumflex coronary artery with either balloon inflation or deployment of a tantalum stent. At 4 weeks, they were killed and the injured vessels processed for histopathologic analysis. Intimal area, lumen area and maximal intimal thickness were measured. The degree of stenosis was expressed as residual lumen area (lumen area/intimal area ratio). RESULTS: Vessels injured by either method demonstrated significant intimal smooth muscle proliferation leading to reduction in lumen area. In the 18 stented vessels residual lumen area measured 0.64 +/- 0.18 and maximal intimal thickness measured 0.6 +/- 0.3 mm; in the 15 balloon-injured vessels these values were 0.75 +/- 0.18 and 0.4 +/- 0.3 mm, respectively (p less than 0.05). In addition, most stented vessels had reactive inflammatory infiltrates surrounding the stent wires composed of lymphocytes, histiocytes and many eosinophils. CONCLUSIONS: These data indicate that coronary artery injury in swine with either balloon inflation or stenting leads to intimal smooth muscle cell proliferation similar to that seen in human restenosis. The degree of intimal proliferation appears to be greater after stenting than after balloon injury. Intracoronary stenting in swine is associated with a marked inflammatory reaction around the stent wires. These models may be helpful in planning systemic and local antirestenosis strategies.

Angioplasty, Balloon, Coronary↗
PubMed1991

Restenosis following coronary angioplasty.

Restenosis is the most important problem limiting the success of coronary angioplasty. Clinically, restenosis is seen in approximately one-third of patients undergoing percutaneous transluminal coronary angioplasty. Several clinical and angiographic risk factors have been identified which may contribute to the development of restenosis. Histopathologic studies indicate that restenosis is characterized by intimal proliferation of smooth muscle cells in a loose connective tissue matrix. These intimal lesions are associated predominantly with the nonatheromatous portion of the vessel wall. Thinning of the media of the plaque-free wall and marked fragmentation of the internal elastic lamina are also seen. Traumatic injury of the vessel wall during angioplasty probably triggers a series of cellular and subcellular events which may ultimately lead to myointimal proliferation and restenosis. Although the exact mechanism by which this occurs is unknown, several factors may enhance smooth muscle cell growth and therefore may play a role in the development of restenosis. These include platelet deposition, mechanical stretching of the media, inflammation of the vessel wall, the activity of growth factors, and alterations in vessel geometry. These possible mechanisms of restenosis suggest several potential ways to limit the proliferative response to vascular injury. Anticoagulants and platelet antagonists, direct inhibitors of smooth muscle proliferation, anti-inflammatory agents, growth factor inhibitors, and new devices which improve final vessel geometry are currently being tested as methods to curb restenosis. Unfortunately, no treatment has yet been shown to reduce significantly the rate of restenosis following angioplasty. The problem of restenosis will most likely be solved by better understanding of the basic molecular and biologic phenomena involved in vascular injury and repair.

Angioplasty, Balloon, Coronary↗
PubMed1991

Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy.

Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin-specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM.

Adult↗
PubMed1991

Incidence of myocarditis. A 10-year autopsy study from Malmö, Sweden.

Although myocarditis has been known for almost two centuries, data in regard to its incidence have varied widely. Autopsy studies have reported an incidence of 3.5% to as high as 10%. The main reason for such diversity of data appears to be the lack of unanimity as to what constitutes myocarditis. Recently, definitions of myocarditis have been proposed and precise criteria for the morphologic recognition of myocarditis have been published. In this study an analysis of 12,747 consecutive autopsies performed from 1975 to 1984 at Malmö (Sweden) General Hospital was carried out. Applying the newly proposed histologic criteria, the diagnosis of myocarditis was made in 136 cases, which constitute 1.06% of the autopsy population studied. This rate of myocarditis incidence at postmortem is lower by far than rates previously published.

Adult↗
PubMed1990

Hypertrophic cardiomyopathy evolving into a hypokinetic and dilated left ventricle: coronary embolization as a probable pathogenetic mechanism.

A long-term follow-up (9 years) in a patient with hypertrophic cardiomyopathy revealed an evolution to a hypokinetic and dilated left ventricle. The patient underwent heart transplantation, and therefore the native heart was available for morphologic studies. Gross and microscopic stigmata of hypertrophic cardiomyopathy were present, as well as evidence of left ventricular dilatation. Multiple myocardial scars in both ventricles indicated past ischemic episodes, most probably due to coronary embolization from left ventricular mural thrombi. Other possible pathogenetic mechanisms for the progression of hypertrophic cardiomyopathy to a dilated one are discussed.

Cardiomyopathy, Dilated↗
PubMed1989

Histopathologic phenomena at the site of percutaneous transluminal coronary angioplasty: the problem of restenosis.

Seventeen postangioplasty cases were morphologically studied at postmortem. Four of the eleven, early and intermediate cases (few hours to 1 month from angioplasty to death), revealed intraluminal thrombi, although in only two cases were those thrombi occlusive. Almost all of the nine early cases (eight of nine) exhibited intimal disruptions. Except for two of these cases in which circumferential and/or longitudinal dissections were present, the remainder of the intimal cracks were superficial and of limited extent. Limited dissection between intima and media is not considered a serious or detrimental local event. The early cases showed an aneurysmal dilatation of the plaque-free segment of the arterial wall in eccentric plaques. This finding was interpreted as the result of uneven distribution of the dilating force (circumferential stress) on the aterial wall. Late cases (survival over 1 month) revealed characteristic medial and intimal lesions indicative of the initial dilatation injury. It is hypothesized that intrinsic arterial wall changes (medial disruption) at the plaque-free segment and the resulting altered arterial geometry at the site of dilatation have a significant hemodynamic effect on the vascular conduit and may enhance and sustain the myoproliferative intimal response.

Adult↗
PubMed1989

Potential risks in retrovenous revascularization of the myocardium.

Retrovenous perfusion of the myocardium via the coronary sinus and cardiac veins was one of the earliest attempted forms of myocardial revascularization. Although coronary artery revascularization has almost completely replaced venous revascularization as the procedure of choice, the latter approach is still occasionally performed. We present two cases of hemorrhage within viable and nonviable myocardium noted at autopsy in patients who had undergone retrovenous revascularization hours before death. The two cases illustrate a complication of this procedure that has not previously been emphasized.

Aged↗
PubMed1989

Allograft heart accelerated atherosclerosis: evidence for cell-mediated immunity in pathogenesis.

The problem of accelerated atherosclerosis in the allograft heart continues to adversely effect the long term survival of transplant patients. Most traditional risk factors influencing atherogenesis do not appear to play an important role in accelerated atherosclerosis. Additional causative factors proposed in recent years are not without controversy. An immune-mediated endothelial damage by cytotoxic B-cell antibodies as the initial injury in the induction of accelerated atherosclerosis has not been confirmed on morphologic grounds. This study is based on six cases (four autopsies and two explanted hearts) from transplant patients whose hearts were examined at different post-transplantation intervals (24 h to 14 mo). Our morphologic findings of a segmental coronary vasculitis involving primarily the outer two-thirds of the media and adventitia suggest that the early vascular manifestations may reflect tissue rejection similar to that seen in the myocardium. Furthermore, our findings from the medium size coronary arteries are suggestive of a cell-mediated immune injury probably directed against the smooth muscle cells of the media. Although the end result (occlusive coronary lesion) may reveal some morphologic similarities in both naturally occurring atherosclerosis and accelerated atherosclerosis, the pathogenetic mechanisms involved in these two conditions may differ.

Adult↗
PubMed1988

Characterization of human cardiac infiltrating cells post transplantation. 1. Phenotypic and functional alloreactivity.

Sequential cardiac biopsies from patients post transplantation were studied for histological evidence of grades of rejection, the immunophenotype of the mononuclear cell infiltrate if present and, in addition, aliquots of the same biopsy were cultured in vitro with medium containing interleukin-2. The exuding mononuclear cells were expanded and bulk cultures and T cell lines resulting from this were evaluated phenotypically and functionally for donor specific alloreactivity. Results of these studies demonstrate: (1) No strict correlation of histological rejection grades with immunophenotype or degree of mononuclear cell infiltrate. (2) The mononuclear cell cultured from 102 biopsies yielded 47 relatively pure CD4+ T cell cultures and 12 cultures enriched for CD4+ T cells, 16 relatively pure CD8+ T cell cultures and 15 cultures enriched for CD8+ T cells, 7 cultures which consisted of dual marked CD4+ CD8+ T cells and 5 which were negative for both CD4 and CD8 but expressed CD3. (3) Of the 59 total CD4+ T cells, 6 demonstrated donor specific CTL reactivity and of the 31 CD8+ T cells, 26 demonstrated donor specific CTL activity. (4) None of the CD4+ CD8+ T cell cultures demonstrated CTL reactivity and all 5 of the CD3+ CD4- CD8- T cell cultures demonstrated potent donor specific CTL activity. (5) Of the 102 cultures, 89 showed donor specific PLT function. (6) High MHC-Class I expression by cardiac myocytes correlated with high frequency of CTL cultures. These data provide a summary of the phenotype and functional analysis of T cells in cardiac biopsy specimens and provide valuable reagents for further studies on the mechanisms involved in human cardiac allograft rejection.

Antibodies, Monoclonal↗
PubMed1987

Idiopathic cardiomyopathies. A review of pathologic studies and mechanisms of pathogenesis.

The purpose of this article is to provide a critical review of our current knowledge of the pathogenic mechanisms of human cardiomyopathy in the context of accepted morphologic findings (gross, microscopic, ultrastructural) and the clinical presentation of this disease. It is our intent to emphasize the numerous difficulties encountered in categorizing patients with cardiomyopathy to pursue investigations in the pathogenesis and origins of this puzzling cardiac condition. It is our belief that such difficulties stem primarily from the existing classification of cardiomyopathies, which is mostly empirical and somewhat vague. This is particularly true in regard to the dilated cardiomyopathies that probably encompass multiple entities grouped under the umbrella of cardiomegaly and dilation. The article's objective is to summarize clinical symptoms and signs, modalities of diagnostic investigations, and prognosis for each category of cardiomyopathy. However, the main purpose of this article is to present recent findings on the origins, possible autoimmune basis of the disease, and results of immunologic studies in patients with cardiomyopathy.

Antibody Formation↗
PubMed1976

Myxoma of the heart: clinical and experimental observations.

During the past 12 years, 13 patients with atrial (10 left and 3 right) myxoma have been treated. The tumors of the left atrium produced signs and symptoms of mitral valve obstruction and/or subacute bacterial endocarditis and those of the right atrium manifestations of tricuspid valve disease or of pulmonary embolus or hypertension. The diagnosis was established by angiocardiography in 8 patients, at surgery performed for suspected mitral stenosis in 3 patients, and at autopsy in 2 patients. Resection of the atrial myxoma alone in 5 patients or with atrial septum where the atrial myxoma was attached in 4 or with the whole right atrial wall where the atrial myxoma was attached in one patient was performed and all are doing well without evidence of recurrence. Studies of experimentally produced 1.5-3 cm in diameter left atrial thrombus in 30 dogs divided into 5 groups and followed cineangiocardiographically and sacrificed from 14 days to 6 months indicated that the implanted thrombus is absorbed over a 3 to 6 month period. These experimental and human left atrial thrombi were found to be histologically and histochemically different from human atrial myxomas. The electron microscopic studies performed on some of the resected atrial myxomas suggested that the atrial myxoma cells are active cells of endotheilial origin. These observations suggest that atrial myxoma is a primary tumor of the heart which can mimic other clinical entities, and the results of its surgical treatment are gratifying and long lasting.

Angiocardiography↗