Mitochondrial swelling and incipient outer membrane rupture in preapoptotic and apoptotic cells.

Outer mitochondrial membrane (OMM) rupture was first noted in isolated mitochondria in which the inner mitochondrial membrane (IMM) had lost its selective permeability. This phenomenon referred to as mitochondrial permeability transition (MPT) refers to a permeabilized inner membrane that originates a large swelling in the mitochondrial matrix, which distends the outer membrane until it ruptures. Here, we have expanded previous electron microscopic observations that in apoptotic cells, OMM rupture is not caused by a membrane stretching promoted by a markedly swollen matrix. It is shown that the widths of the ruptured regions of the OMM vary from 6 to 250 nm. Independent of the perforation size, herniation of the mitochondrial matrix appeared to have resulted in pushing the IMM through the perforation. A large, long focal herniation of the mitochondrial matrix, covered with the IMM, was associated with a rupture of the OMM that was as small as 6 nm. Contextually, the collapse of the selective permeability of the IMM may precede or follow the release of the mitochondrial proteins of the intermembrane space into the cytoplasm. When the MPT is a late event, exit of the intermembrane space proteins to the cytoplasm is unimpeded and occurs through channels that transverse the outer membrane, because so far, the inner membrane is impermeable. No channel within the outer membrane can expose to the cytoplasm a permeable inner membrane, because it would serve as a conduit for local herniation of the mitochondrial matrix.

Chronic American trypanosomiasis: parasite persistence in endomyocardial biopsies is associated with high-grade myocarditis.

Myocyte diameter, fractional area of collagen, intensity of myocarditis and parasite persistence (explored by immunohistochemistry and PCR) were evaluated in serial sections of endomyocardial biopsies from 29 outpatients with chronic chagasic cardiopathy. The patients, 25 males and four females with a mean (S.D.) age of 43 (9) years, were subsequently followed up for 3-2861 days (median=369 days). During this follow-up, 16 (55%) of the patients died. The biopsies revealed myocarditis in 25 (86%) of the patients and high-grade myocarditis in 14 (56%). Although immunohistochemistry failed to demonstrate Trypanosoma cruzi antigens in any of the samples, five (33%) of the 15 biopsies successfully tested in the PCR-based assay for T. cruzi DNA were found positive, indicating parasite persistence. There was a significant positive association between myocardial parasite persistence and high-grade myocarditis (P=0.014); five (71%) of the seven endomyocardial biopsies with high-grade myocarditis that were successfully tested in the PCR assays showed persistent T. cruzi DNA. The survival time of the patients was not, however, found to be significantly associated with myocardial parasite persistence, any of the morphometric measurements taken, or the presence or intensity of myocarditis.

Locally produced survival cytokines IL-15 and IL-7 may be associated to the predominance of CD8+ T cells at heart lesions of human chronic Chagas disease cardiomyopathy.

Human chronic Chagas disease cardiomyopathy (CCC) is an inflammatory-dilated cardiomyopathy occurring years after infection by the protozoan Trypanosoma cruzi. The heart inflammatory infiltrate in CCC shows a 2:1 predominance of CD8(+) in relation to CD4(+) T cells, with a typical Th1-type cytokine profile. However, in vitro expansion of infiltrating T cells from heart biopsy-derived fragments with interleukin-2 (IL-2) and phytohaemagglutinin leads to the outgrowth of CD4(+) over CD8(+) T cells. We hypothesized that survival cytokines, such as IL-2, IL-7 and IL-15 might be differentially involved in the growth and maintenance of heart-infiltrating and peripheral CD8(+) T cells from CCC patients. We found that IL-7 and IL-15 were superior to IL-2 in the expansion and viability of CD8(+) T cells from both PBMC and heart-infiltrating T-cell lines from CCC patients, and the combination of the three cytokines showed synergic effects. Heart-infiltrating CD8(+) T cells showed higher expression of both IL-15R alpha and gamma(c) chain than CD4(+) T cells, which may explain the improvement of CD8(+) T-cell growth in the presence of IL-2 + IL-7 + IL-15. Immunohistochemical identification of IL-15 and the higher mRNA expression of IL-15R alpha, IL-7 and gamma(c) chain in CCC heart tissues compared with control individuals indicate in situ production of survival cytokines and their receptors in CCC hearts. Together, our results suggest that local production of IL-7 and IL-15 may be associated with the maintenance and predominance of CD8(+) T cells, the cells effecting tissue damage in CCC hearts.

Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation?

An emerging clinical entity that reproduces clinical manifestations similar to those observed in Lyme disease (LD) has been recently under discussion in Brazil. Due to etiological and laboratory particularities it is named LD-like syndrome or LD imitator syndrome. The condition is considered to be a zoonosis transmitted by ticks of the genus Amblyomma, possibly caused by interaction of multiple fastidious microorganisms originating a protean clinical picture, including neurological, osteoarticular and erythema migrans-like lesions. When peripheral blood of patients with LD-like syndrome is viewed under a dark-field microscope, mobile uncultivable spirochete-like bacteria are observed. PCR carried out with specific or conservative primers to recognize Borrelia burgdorferi sensu stricto or the genus Borrelia has been negative in ticks and in biological samples. Two different procedures, respectively involving hematoxylin and eosin staining of cerebrospinal fluid and electron microscopy analysis of blood, have revealed spirochetes not belonging to the genera Borrelia, Leptospira or Treponema. Surprisingly, co-infection with microorganisms resembling Mycoplasma and Chlamydia was observed on one occasion by electron microscopy analysis. We discuss here the possible existence of a new tick-borne disease in Brazil imitating LD, except for a higher frequency of recurrence episodes observed along prolonged clinical follow-up.

Description of Lyme disease-like syndrome in Brazil: is it a new tick borne disease or Lyme disease variation?

An emerging clinical entity that reproduces clinical manifestations similar to those observed in Lyme disease (LD) has been recently under discussion in Brazil. Due to etiological and laboratory particularities it is named LD-like syndrome or LD imitator syndrome. The condition is considered to be a zoonosis transmitted by ticks of the genus Amblyomma, possibly caused by interaction of multiple fastidious microorganisms originating a protean clinical picture, including neurological, osteoarticular and erythema migrans-like lesions. When peripheral blood of patients with LD-like syndrome is viewed under a dark-field microscope, mobile uncultivable spirochete-like bacteria are observed. PCR carried out with specific or conservative primers to recognize Borrelia burgdorferi sensu stricto or the genus Borrelia has been negative in ticks and in biological samples. Two different procedures, respectively involving hematoxylin and eosin staining of cerebrospinal fluid and electron microscopy analysis of blood, have revealed spirochetes not belonging to the genera Borrelia, Leptospira or Treponema. Surprisingly, co-infection with microorganisms resembling Mycoplasma and Chlamydia was observed on one occasion by electron microscopy analysis. We discuss here the possible existence of a new tick-borne disease in Brazil imitating LD, except for a higher frequency of recurrence episodes observed along prolonged clinical follow-up.

Relevance of apoptosis and cell proliferation for survival of patients with dilated cardiomyopathy undergoing partial left ventriculectomy.

BACKGROUND: Cardiomyocyte apoptosis as well as proliferation have been described in congestive heart failure, but their clinical relevance remains unclear. In order to clarify whether apoptosis and cell proliferation occur in patients with idiopathic dilated cardiomyopathy and whether their degree in left ventricle fragments resected during partial left ventriculectomy has any influence on the outcome after this surgery, we compared their occurrence in four groups of patients: group A, short-term survivors (n = 18); group B, deaths within 6 months of the surgery (n = 13); group C, long-term survivors (n = 12); and Group D, deaths within 60 months (n = 19). DESIGN: Apoptotic cardiomyocytes and interstitial cells were quantified in left ventricle fragments from 31 patients with idiopathic-dilated cardiomyopathy using the TUNEL assay. Cell proliferation was quantified in parallel sections by KI-67 immunohistochemistry. RESULTS: Apoptotic cells were present in the majority of cases (n = 24) and proliferative cells in all cases. Whereas there was no significant difference regarding all parameters examined between Groups A and B, there was a highly significant difference between Groups C and D in the number of apoptotic cardiomyocytes (P = 0.012) and apoptotic interstitial cells (P = 0.006). There was no significant relationship between apoptotic cardiomyocytes and KI-67-positive cardiomyocytes, but a negative correlation between apoptotic interstitial cells and KI-67-positive interstitial cells (r = -0.383; P = 0.028). CONCLUSION: Cardiomyocyte apoptosis and proliferation occur in the majority of patients with idiopathic-dilated cardiomyopathy. High numbers of apoptotic cardiomyocytes and apoptotic interstitial cells are significantly related to a bad late outcome after partial left ventriculectomy.

Coenzyme Q10 exogenous administration attenuates cold stress cardiac injury.

The influence of coenzyme Q10 (CoQ10) in cold stress test (-15 degrees C for 4 hours) cardiac functional impairment was studied in isolated isovolumic heart of control rats (C; n=12) and of placebo (P; n=11) and treated rats (CoQ10; n=10). In addition, electron microscopic evaluation of left ventricular (LV) slices (n=3 in each group) allowed us to analyze the myocardial ultrastructure. Maximal values of developed pressure (DPmax) were similarly decreased in cold stressed animals (C=129+/-3.9 mmHg; P=106+/-6.7 mmHg; CoQ10=91+/-3.9 mmHg); however, volume-induced enhancement of pressure generation (slope of DP volume relations: C=0.248+/-0.0203 mmHg / microl; P=0.2831+/-0.0187 mmHg / microl; CoQ10=0.2387 ( 0.0225 mmHg / microl; p > 0.05), and the duration of systole (C=80+/-1.6 ms; P=78+/-1.3 ms; CoQ10=80+/-2.7 ms) were not altered. Myocardial relaxation, evaluated by the relaxation constant (C=39+/-1.9 ms; P=42+/-3.4 ms; CoQ10=51+/-6.0 ms), as well as resting stress / strain relations were unaffected by cold stress. Myocardial samples showed that pretreatment with CoQ10 attenuates myofibrillar and mitochondrial lesions, and prevents mitochondrial fractional area increase (P: 53.11%>CoQ10: 38.78%=C: 33.87%; p< 0.005) indicating that the exogenous administration of CoQ10 can reduce cold stress myocardial injury.

Atheromas that cause fatal thrombosis are usually large and frequently accompanied by vessel enlargement.

Several lines of clinical evidence show that AMI frequently occurs at sites with mild to moderate degree of coronary stenosis. The degree of luminal stenosis depends on plaque deposition and degree of vessel remodeling, features poorly assessed by coronary angiography. This postmortem study tested the hypothesis that the size of coronary atheroma and the type of remodeling distinguish culprit lesion responsible for fatal AMI from equi-stenotic nonculprit lesion in the same coronary tree. The main coronary branches from 36 consecutive patients with fatal AMI were studied. The culprit lesion (Group 1) and an equi-stenotic nonculprit segment (Group 2) obtained in measurements of another coronary branch from the same patient were compared. Morphometry and plaque composition was assessed in both groups. Compared to Group 2, Group 1 had larger areas of: plaque 9.6 vs. 4.7 mm(2), vessel 12.7 vs. 7.4 mm(2) and lumen 1.7 vs. 1.2 mm(2); (P< .01). Positive remodeling was more frequent in Group 1 than Group 2: 21/30 (70%) vs. 8/26 (31%). Plaque area correlated positively with lipid core and macrophages and negatively with fibrosis and smooth muscle cells. Atherosclerotic plaques that cause fatal thrombosis are more frequently positively remodeled and tend to be larger than nonculprit plaques with the same degree of cross-sectional stenosis. We tested whether arterial remodeling and plaque size vary between segments containing a fatal thrombosed plaque versus an equi-stenotic nonculprit plaque. Culprit vessel segments had higher cross-sectional areas of intimal plaque and of vessel wall than equi-stenotic nonculprit plaques. The cross-sectional area of the vessel correlated positively with both the lipid core area and CD68(+) macrophage content, and negatively with fibrosis area and smooth muscle cell content. These results add elements explaining limitations of angiography in identifying plaques and provide new insights into the role of remodeling in plaque instability.

Histopathological findings in skeletal muscle used in human dynamic cardiomyoplasty.

Patients submitted to dynamic cardiomyoplasty had an initial clinical improvement followed by a decrease in cardiac failure indices. A histopathological study of the skeletal muscle was undertaken to explain this. Latissimus dorsi fragments from 15 patients submitted to dynamic cardiomyoplasty in a 1:1 (heart beat:muscle stimulation) conditioning were analysed by light microscopy. The interval between surgery and obtaining the specimens (13 from necropsies, two from heart transplants) ranged from 37 days to 6 years. Nuclear clumps and internalization, the presence of round fibres, inflammation, and fibrosis were analysed semi-quantitatively; the thickness of muscle fibres and the percentage of tissue fat were measured by image analysis. The quantitative data were also compared, in 12 cases, with gender- and age-matched necropsy controls. The mean thickness of muscle fibres in cases and controls was 27.21+/-5.33 and 40.84+/-9.42 microm, respectively (p=0.001). The percentage of tissue fat in cases and controls was 12.04+/-12.66% and 0.93+/-0.91%, respectively (p=0.008). The duration of grafts correlated positively with the quantity of nuclear clumps (R=0.80, p<0.001) and round fibres (R=0.53, p=0.04), as well as with the percentage of tissue fat (R=0.68, p=0.005). Accordingly, a negative correlation was found between the duration of grafts and the mean diameter of fibres, characterizing muscle atrophy (R=-0.66, p=0.01). The longer the post-surgical period, the more intense the degenerative lesions. This study shows that skeletal muscle used in human dynamic cardiomyoplasty may atrophy and be replaced by fat when stimulation is synchronized to every cardiac beat. These findings could play a role in explaining the long-term results of this surgical procedure.

Cardiac rhabdomyomas exhibit a fetal pattern of atrial natriuretic peptide immunoreactivity.

Rhabdomyomas are the most common heart tumors seen in infancy. However, whether they represent hamartomas or true neoplasms derived from cardiomyocytes is still controversial. The fetal pattern of atrial natriuretic peptide (ANP) expression (predominant in the atrial and ventricular subendocardium) becomes altered during the early postnatal period to that typical of the adult (all atrial cardiomyocytes and some cells in the ventricular impulse-conducting system). To better comprehend the nature and origin of cardiac rhabdomyomas, we investigated the immunohistochemical expression of ANP in seven surgically excised ventricular specimens and two necropsy cases of multiple, atrial, and ventricular rhabdomyomas in children aged 1 to 34 days. Immunogold labeling for ANP at the ultrastructural level was also performed on three ventricular tumors. Although all atrial tumors were immunoreactive for ANP, these usually showed a variable number of faintly positive cardiomyocytes, contrasting with the diffuse and intense immunoreactivity of the surrounding atrial myocardium. ANP was detected in the ventricular tumors of five (56%) of the nine cases. The positive ventricular tumor cells predominated in the subendocardium and areas with prominent fibrous tissue, usually around blood vessels. Immunoelectron microscopy of the ventricular tumors demonstrated rare, positive cytoplasmic granules surrounded by membranes, usually located near the nuclei. We conclude that cardiac rhabdomyomas exhibit a fetal pattern of ANP immunoreactivity, which suggests delayed maturation of the tumoral cardiomyocytes, reinforcing the notion that cardiac rhabdomyomas are fetal hamartomas.

Systematic mapping of hearts from chronic chagasic patients: the association between the occurrence of histopathological lesions and Trypanosoma cruzi antigens.

To investigate the role played by Trypanosoma cruzi in the pathogenesis of chronic chagasic cardiopathy, the myocardiums of 12 hearts from individuals who had this condition were mapped in detail. Attempts were made to associate the histopathological lesions observed with the presence of parasitic antigens in the affected tissue. Samples from 26 regions of each heart were submitted to histological analysis and immunostained for the presence of T. cruzi. All cases showed at least one positive region for antigens, but the quantity of antigen detected varied greatly. The regions showing the greatest pathological changes were the inferior atrial septum, the basal and apical portions of the ventricular septum, and the posterior basal and lateral pre-apical regions of the left ventricle. The posterior wall of the right atrium and the posterior basal wall of the left ventricle presented the greatest intensities of inflammation. Fibrosis was intense in the right atrium, the posterior basal and pre-apical left ventricular free walls and the apex. The regions in which T. cruzi antigens were detected showed the most intense inflammation. However, as there was no significant correlation between the intensity of the lesions and the quantity of parasitic antigen, other mechanisms, such as auto-immunity or hypersensitivity, may stimulate the inflammation.

Detection of Mycoplasma pneumoniae and Chlamydia pneumoniae in ruptured atherosclerotic plaques.

This paper reports what is apparently the first observation of Mycoplasma pneumoniae in association with Chlamydia pneumoniae in thrombosed ruptured atheromas. We performed electron microscopy and in situ hybridization in specimens from three patients who died of acute myocardial infarction. These patients had typical symptoms of acute ischemic syndrome. Mycoplasmas were present mainly in the lipid core of the ruptured thrombosed plaque. Vulnerable atheromas are rich in cholesterol and may favor the growth of mycoplasmas, the only microorganisms that require cholesterol for survival. We suggest that the association of Mycoplasma pneumoniae and Chlamydia pneumoniae may increase the virulence of these microorganisms, favoring proliferation, plaque inflammation and possibly plaque rupture.

Detection of Mycoplasma pneumoniae and Chlamydia pneumoniae in ruptured atherosclerotic plaques

This paper reports what is apparently the first observation of Mycoplasma pneumoniae in association with Chlamydia pneumoniae in thrombosed ruptured atheromas. We performed electron microscopy and in situ hybridization in specimens from three patients who died of acute myocardial infarction. These patients had typical symptoms of acute ischemic syndrome. Mycoplasmas were present mainly in the lipid core of the ruptured thrombosed plaque. Vulnerable atheromas are rich in cholesterol and may favor the growth of mycoplasmas, the only microorganisms that require cholesterol for survival. We suggest that the association of Mycoplasma pneumoniae and Chlamydia pneumoniae may increase the virulence of these microorganisms, favoring proliferation, plaque inflammation and possibly plaque rupture

Upregulation of adhesion molecules and class I HLA in the myocardium of chronic chagasic cardiomyopathy and heart allograft rejection, but not in dilated cardiomyopathy.

The immunohistochemical expression of adhesion molecules and class I HLA in chronic chagasic cardiomyopathy were compared with heart allograft rejection and dilated cardiomyopathy, to obtain new knowledge on the occurrence of autoimmunity and inflammation in the pathogenesis of chronic chagasic cardiomyopathy. Semiquantitative immunohistochemistry was performed for CD8+ T cells, ICAM-1, VCAM-1, LFA-1, and class I HLA in frozen sections of myocardial biopsies from patients presenting chronic chagasic cardiomyopathy (group I, n = 12), heart allograft rejection (group II, n = 9) or dilated cardiomyopathy (group III, n = 9). A high mean number of CD8+ T cells/mm(2) was present in group I (18.26) and group II (28.60), but not in group III (0.83). The frequency of high expression for ICAM-1 and VCAM-1 on the endothelial and interstitial cells, and for class I HLA on the cardiomyocytes was greater in group I (100%, 33.3%, and 83.3%, respectively) and group II (100%, 66.7%, and 77.8%, respectively), compared to group III (66.7%, 0%, and 0%, respectively). ICAM-1 and VCAM-1 probably participate in the development of the lymphocytic inflammatory infiltrate present in chronic chagasic cardiomyopathy, as seen in heart allograft rejection. The overexpression of adhesion molecules and the induction of class I HLA on the cardiomyocytes are probably related to the high cytokine levels at the inflammatory sites in chronic chagasic cardiomyopathy. Although the induction of class I HLA on the cardiomyocytes is consistent with an autoimmune reaction, it should not be considered as irrefutable evidence for autoimmunity in chronic chagasic cardiomyopathy. The differential expression of adhesion molecules and class I HLA in dilated cardiomyopathy compared to chronic chagasic cardiomyopathy suggests differences in the pathogenesis of these cardiomyopathies.

Autopsy findings in early and late postoperative death after partial left ventriculectomy.

BACKGROUND: Partial left ventriculectomy (PLV) is an alternative to heart transplantation for patients with severe heart failure. However, this procedure is accompanied by high morbidity and mortality. Therefore, we studied the hearts of 12 patients who underwent this procedure to increase our understanding of the causes of bad outcome. METHODS: We analyzed the autopsy hearts of 11 of 16 patients who died after PLV, and one heart from a patient who underwent heart transplantation. RESULTS: Six patients died less than 30 days postoperatively, 4 of cardiogenic shock, 1 of arrhythmia, and 1 of coagulopathy. Five patients died from 36 to 120 days after the procedure, 4 of cardiogenic shock and 1 of arrhythmia. The patient who underwent heart transplantation had a cardiogenic shock 230 days after PLV. Ten hearts weighed more than 500 g and nine had myocardial infarction that extended to the papillary muscles. Four patients had infarction of both papillary muscles and 3 of them had episodes of arrhythmia, suggesting some relation between these events. CONCLUSIONS: We found several important morphologic clues for bad outcome: infarction of both papillary muscles, which may be associated with the development of arrhythmia, and myocardial infarction and pericardial hemorrhage, which may contribute to the outcome of heart failure.

CMV and transplant-related coronary atherosclerosis: an immunohistochemical, in situ hybridization, and polymerase chain reaction in situ study.

Accelerated graft coronary atherosclerosis is the main obstacle to long-term survival in patients who have had a heart transplant. A possible involvement of the human cytomegalovirus (HCMV) in this type of coronary atherosclerosis has been postulated by many authors but has not been definitively demonstrated. In an attempt to clarify the role of HCMV infection in the pathogenesis of this complication, we looked for in situ antigens or DNA of HCMV in 30 coronary artery segments obtained at necropsy from patients who had undergone orthotopic cardiac transplantation at the São Paulo Heart Institute. We tried to correlate these HCMV markers with the presence of inflammation and/or atherosclerosis in histologic sections. The patients were grouped as follows: GI, less than 170 days of graft survival and absent/mild atherosclerosis; GII, more than 170 days of graft survival and absent/mild atherosclerosis; GIII, more than 170 days of graft survival and severe/moderate atherosclerosis (170 days was the shortest graft survival time associated with atherosclerosis). The search for HCMV genome and antigens in the coronary artery sections was performed using immunohistochemistry, in situ hybridization, and polymerase chain reaction in situ techniques. Immunohistochemistry and in situ hybridization revealed no evidence of HCMV in all 30 cases. Polymerase chain reaction in situ revealed scarce HCMV-positive lymphocytes in two cases (one each from GI and GIII) located in the adventitial layer. These findings preclude a direct role for the HCMV in the pathogenesis of accelerated graft coronary atherosclerosis. However, the possibility of an indirect effect of the virus, such as an immune-mediated inflammatory response by the host that increases the expression of histocompatibility antigens, leading to tissue injury, cannot be excluded.

Imaging Trypanosoma cruzi within tissues from chagasic patients using confocal microscopy with monoclonal antibodies.

Confocal fluorescence microscopy combined with differential interference contrast imaging of tissues from chagasic patients enabled the unequivocal identification of the parasite Trypanosoma cruzi. Using different monoclonal antibodies that indicate the parasite form and replication stage in conjunction with DNA labelling, specimens derived from distinct clinical forms of the disease were examined. Intracellular amastigote forms of the parasite were clearly detected in heart, brain, skin, lung, and kidney. Dividing amastigotes as well as trypomastigote forms were recognized in samples obtained from patients undergoing either acute-phase or some form of reactivation caused by immunosuppression.

Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas' disease: a three dimensional confocal microscopy study.

OBJECTIVE: To analyse the morphological aspects of the extracellular matrix and microcirculation to clarify whether chronic Chagas' cardiopathy (CCC) is an accurate model to study the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). DESIGN: Thick histological myocardial sections were prepared to analyse collagen, and microcirculation was examined during confocal laser and light microscopy. SETTING: The specimens were prepared at the pathology service of the Heart Institute of São Paulo, Brazil. PATIENTS: Nine control hearts, eight IDCM hearts, and 10 CCC hearts were studied after necropsy. MAIN OUTCOME MEASURES: The number of collagen struts per 100x field, the area of fibrosis (%), and the diameters of arterioles and capillaries were measured in each heart to establish outcome. RESULTS: A smaller number (mean (SD)) of collagen struts was seen in the hearts in the IDCM group (9.1 (4.1)) than in the control (22.4 (3.2)) (p < 0.05) or CCC (15.7 (7.4)) (p > 0.05) groups. Fibrosis was greater in the CCC hearts (13.8 (10.5)%) than in the IDCM hearts (5.9 (6.6)%) (p > 0.05). Major increases in arteriole (65.4 (9.9) microm) and capillary (9.9 (1.7) microm) diameters were seen in the CCC hearts but not in the IDCM hearts (arteriole diameter 40.3 (7.9) microm; capillary diameter 7.9 (1.3) microm). CONCLUSIONS: Hearts demonstrating CCC and IDCM present different extracellular and microvessel alterations. This suggests that distinct pathogenic mechanisms are responsible for each condition and that CCC is not an effective model to study IDCM.

Histological evidence of concomitant intramyocardial and epicardial vasculitis in necropsied heart allografts: a possible relationship with graft coronary arteriosclerosis.

BACKGROUND: The significance of medial lymphocytic vasculitis in intramural coronary vessels in heart transplantation is very poorly understood. This study was designed to identify histological evidence of an association between the presence of epicardial coronary lesions and the occurrence of intramyocardial vasculitis and/or myocardial ischemia. METHODS: We analyzed the frequency of medial vasculitis and other myocardial histological alterations in a retrospective study of 24 human cardiac allografts from patients who died of ischemic heart disease and/or myocardial rejection. RESULTS: Medial lymphocytic vasculitis in the myocardium was associated with vasculitis in the vasa vasorum of the epicardial coronary arteries and the presence of microfoci of acute myocardial infarction but was independent of the occurrence of myocardial fiber rejection. Chronic graft epicardial arteriopathy revealed two patterns of lesions. One pattern was similar to that of usual atherosclerosis, compromising mainly the proximal segments of the coronary artery, and was not associated with intramural vasculitis. The other pattern demonstrated diffuse involvement of the epicardial artery associated with vasculitis of its vasa vasorum and lymphocytic vasculitis of the intramural vessels. This second type of epicardial coronary lesion seemed to evolve to fibrotic arteries with thinned walls, frequently demonstrating aneurysmal dilatation with severe fibrosis of the adventitia and poor vasa vasorum. CONCLUSION: Medial vasculitis affecting intramyocardial vessels is associated with adventitial epicardial coronary vasculitis in the transplanted heart. The process of vasculitis may be involved in the development of chronic graft arteriosclerosis and is associated with ischemic myocardial lesions, but seems independent of myocardial fiber rejection.