Increased adventitial mast cells in a patient with coronary spasm.
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Biomedical subjects
Publications and source records attributed to R Virmani.
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Previous studies of saphenous vein (SV) bypass grafts have been either angiographic or morphologic, and few have correlated angiograms with histology. Nine necropsy patients who had received 21 SV implants 12 to 120 months (mean 67 +/- 42) before death were studied. All patients had severe coronary artery disease. Three types of histologic changes were found: atherosclerosis in 9 grafts, fibrointimal proliferation in 8 and total occlusion with fibrosis in 4. All patients had premortem angiograms 0 to 3 months (mean 0.7 +/- 1.1) before death. In 14 of 21 grafts, premortem angiograms accurately reflected the postmortem findings. In 7 grafts, the premortem angiograms either overestimated (4 grafts) or underestimated (3 grafts) the extent of luminal narrowing. Six of the 7 SV implants incorrectly assessed by angiography had fibrointimal proliferation and 1 had atherosclerosis. The presence of smooth muscle in SV implants with fibrointimal proliferation may be a mechanism of spasm or relaxation during angiography, which could cause errors in estimating the degree of stenosis. Nitrates or calcium antagonists may be useful in both assessing the degree of underlying vasomotion in SV grafts and as a therapeutic modality.
To assess the effect of Fluosol-DA treatment on infarct morphology, detailed histologic examination was performed in 17 dogs with permanent proximal left anterior descending coronary artery occlusion. Two of the three groups of dogs received an equal blood volume exchange (40 ml/kg i.v.) with either Fluosol-DA (F) or heparinized autologous blood (H) 30 min post occlusion while being ventilated with 100% oxygen. A third group received no therapy (C). Animals were sacrificed 3 days post occlusion and sections were obtained for light and electron microscopy. Histologic studies showed that infarct size was statistically smaller in dogs treated with F 54 +/- 7% versus heparin 64 +/- 10% treatment or no therapy 79 +/- 6%. Fluosol-DA animals demonstrated decreased inflammatory infiltrate, larger viable subepicardial zones and greater endocardial sparing in the area surrounding the central zone of necrosis. By electron microscopy, perfluorochemical particles were found within endothelial and inflammatory cells in subepicardial zones of infarction. In midmyocardial zones, Fluosol-DA particles were present in capillaries, extracellular spaces and necrotic myocytes. In the normal myocardium Fluosol-DA particles were rarely seen within endothelial cells and never within the interstitium or myocytes. Thus, Fluosol-DA reduces infarct size and alters infarct morphology in the 3 day post permanent coronary occlusion model.
Cardiac rupture occurs in 10 per cent of patients who die with acute myocardial infarction, but the pathogenesis remains unclear. Twenty randomly selected patients with cardiac rupture were reviewed retrospectively at autopsy, and the findings were compared with those of 20 age- and sex-matched control subjects who had died of acute transmural myocardial infarction without rupture. The times from the onset of chest pain to death were similar in the two groups (5.7 +/- 5.8 days for patients with rupture versus 4.2 +/- 4.9 days for control subjects), and there were no differences in the incidences of systemic hypertension, diabetes mellitus, hypercholesterolemia, history of myocardial infarction, or angina pectoris. The severity of coronary atherosclerosis was different in the two groups, with 55 per cent of the patients with cardiac rupture having single-vessel disease and 70 per cent of the patients without cardiac rupture having disease in three vessels. Additionally, the incidence of thrombosis was greater in patients with cardiac rupture than in those without. The inflammatory cell response in each patient was quantitated microscopically (number and type of leukocytes) in ten high-power fields. The inflammatory response was greater in patients with cardiac rupture. The number of eosinophils in the inflammatory response was significantly (P less than 0.01) greater in hearts associated with cardiac rupture (29.5 +/- 4 per cent) than in control hearts (11.7 +/- 3.1 per cent). It is postulated that eosinophils rich in arylsulfatase B, peroxidase, glucuronidase, beta-glycerophosphatase, major basic protein, and eosinophilic cationic protein may further weaken the necrotic myocardium and, in part, determine whether acute myocardial infarction will eventually result in cardiac rupture.
Two-dimensional echocardiographic findings in porcine valve dysfunction were compared with pathologic findings in 10 patients (12 valves). Three specific echocardiographic findings were identified in patients with regurgitant lesions: prolapse, fracture and flail leaflets. Prolapse was associated pathologically with thinning of the leaflets, longitudinal tears close to the ring margin and acid mucopolysaccharide accumulation. Valve fracture was seen with and without prolapse and was accompanied pathologically by small pinpoint perforations or tears of the leaflet. A flail leaflet was seen with a linear tear of the free margin and was associated with calcific deposits. Mild degrees of fracture seen pathologically were missed on the echocardiographic study in five patients. Thickening or calcification, when present in moderate or severe amounts, was correctly identified by echocardiography. When all abnormal features were considered collectively, two-dimensional echocardiography correctly identified at least one of them in all patients. Therefore, two-dimensional echocardiography may prove useful in assessing the source of valvular regurgitation in patients with bioprosthetic valves.
To determine the relation between right ventricular hypertrophy and right ventricular myocardial infarction in patients with chronic lung disease, the records of 28 patients with chronic lung disease, inferior myocardial infarction and significant coronary artery disease (group I) and 20 patients with right ventricular hypertrophy, chronic lung disease without inferior myocardial infarction or significant coronary artery disease (group II) were reviewed. Chronic lung disease was diagnosed by clinical criteria, chest radiographs and pulmonary function tests. All patients had postmortem examinations. Patients in group I were classified into two subgroups: group Ia (without right ventricular hypertrophy) and group Ib (with right ventricular hypertrophy). Right ventricular wall thickness was 3.3 mm +/- 0.5 in group Ia, 6.0 mm +/- 1.1 in group Ib and 8.8 mm +/- 2.4 in group II (group Ia versus Ib, p less than 0.001; group Ia versus II, p less than 0.001; group Ib versus II, p less than 0.001). Eleven patients (78.6%) in group Ib (chronic lung disease with both right ventricular hypertrophy and inferior myocardial infarction) had right ventricular myocardial infarction compared with only 3 patients (21.9%) in group Ia (chronic lung disease without right ventricular hypertrophy and with inferior myocardial infarction) (p less than 0.008). Isolated right ventricular myocardial infarction occurred in four patients (20%) in group II (chronic lung disease with right ventricular hypertrophy, but without evidence of infarction of the left ventricle or significant coronary artery disease). There was no significant difference in the extent of anatomic coronary disease in groups Ia and Ib.(ABSTRACT TRUNCATED AT 250 WORDS)
A 46-year-old woman died from massive bowel infarction. At autopsy, a primary sarcoma was found growing along the intimal surface of the aorta at the level of the celiac axis. Tumor emboli were found in distal aortic branches and most abdominal organs. Immunoperoxidase for Factor VIII and electron microscopy (EM) did not support an endothelial origin. EM showed myofibroblastic differentiation. Review of the literature yields an array of diagnostic histologic terms for these tumors, hampering case comparison. The literature does suggest, however, that the clinical presentation of these rare neoplasms correlates nicely with the location and gross morphology of the lesion. We therefore propose a clinicopathologic classification, categorizing the lesions as intimal (obstructive and nonobstructive) and mural. The former are typically pleomorphic sarcomas and are probably of myofibroblastic origin, whereas the latter are usually leiomyosarcomas or fibrosarcomas that probably originate in the media or adventitia.
The effect of low-dose (15 ml/kg) intracoronary perfluorochemical (Fluosol-DA) on infarct size, regional myocardial blood flow, and ventricular function was studied in 20 anesthetized closed-chest dogs subjected to 11/2 hr of proximal left anterior descending occlusion. In this preparation reperfusion was simulated with fibrinolytic therapy. The animals were randomly assigned one of two treatment groups and given 15 ml/kg of either oxygenated intracoronary perfluorochemical (n = 9) or saline (n = 11). Contrast ventriculograms were obtained at baseline, 1 hr after occlusion, and at 24 hr after reperfusion and were analyzed with a radial fractional shortening method. Regional myocardial blood flow was measured with radioactive microspheres. At 24 hr the area at risk was defined in vivo with monastryl blue staining and the area of necrosis was estimated after incubation of left ventricular slices with triphenyltetrazolium chloride. No significant changes were noted in heart rate, blood pressure, pulmonary capillary wedge pressure, or dP/dt during the experimental protocol. Infarct size was significantly reduced (p less than .02) in the perfluorochemical-treated group, both when expressed as a percentage of the total left ventricular mass (7.9 +/- 1.7% vs 14.7 +/- 2.5%) and as a percentage of the area at risk (20.1 +/- 5.0% vs 46.8 +/- 8.5%). This was associated with significant improvement in fractional shortening in the jeopardized zone at 24 hr after reperfusion. Although endocardial blood flow was significantly greater in the central ischemic zone and lateral region at risk immediately after reperfusion in the perfluorochemical-treated group, no difference was found 1 hr after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
We made continuous electrocardiographic recordings on magnetic tape during 15 episodes of ischemia in five patients with variant angina to determine the characteristics of the QRS changes. Orthogonal leads were used and the electrocardiograms were analyzed visually and by digital computer. Changes were quantified by subtracting baseline electrocardiograms from those obtained during ischemia. Large changes in the QRS occurred during ischemia but the waveform quickly returned to baseline when the episode subsided. In all patients there was prolongation of the QRS duration and an increase in QRS voltage during the terminal 40 msec of the waveform in the lead(s) showing the most marked ST displacement. The increase in the terminal QRS could be represented by a vector directed toward the ischemic zone. In a given patient the amplitude of ST displacement varied between episodes, presumably because of variation in the intensity of ischemia, but the QRS changes were directionally similar in each episode. In two patients there was also a smaller change involving the initial 40 msec of the QRS that could be represented by a vector directed away from the ischemic zone. To determine the possible mechanism for the electrocardiographic changes, ischemic episodes of 120 to 150 sec were produced in seven dogs and electrocardiographic recording and analysis techniques similar to those used in patients were employed. Myocardial conduction velocity was measured in three directions in the ischemic zone and was correlated with simultaneous electrocardiographic recordings from the body surface. The electrocardiographic changes in the dog preparation were virtually identical to those in the patients and strongly correlated with a fall in myocardial conduction velocity. We conclude that the QRS changes during variant angina result from the altered excitation pattern produced by conduction delay in the ischemic zone. The probable cause for the increase in terminal QRS voltage is delayed (and uncancelled) activation of the ischemic zone.
A retrospective autopsy study was performed in 56 patients who had undergone saphenous vein bypass graft (SVBG) surgery 12 to 168 months prior to death. Twenty-five grafts had atherosclerosis, 66 grafts had fibrointimal proliferation, and 26 grafts were fibrotic with total occlusion. No significant differences were noted among the three morphologic groups with regard to age of the patient or number of native coronary arteries severely narrowed. Vein grafts with fibrointimal proliferation occurred with greater frequency in patients with systemic hypertension (p less than 0.001), and atherosclerotic grafts were more prevalent in patients with hypercholesterolemia (p less than 0.02). Therefore, the presence of risk factors may determine the type of change that occurs in saphenous vein bypass grafts: systemic hypertension leads to fibrointimal proliferation, whereas hypercholesterolemia leads to atherosclerotic change.
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We describe two patients with primary sarcoma of the heart in whom metastatic lesions were the first evidence of disease. One patient had a fibrosarcoma of the tricuspid valve with only pulmonary metastases. The second had a pleomorphic sarcoma of the mitral valve with renal and bony metastases. The possibility of a primary cardiac tumor should be considered in patients with occult metastatic sarcoma.
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An autopsy study of 60 patients with fungal infections of the heart was undertaken. The patients ranged in age from 2 months to 79 years. Fifteen of the patients had undergone cardiac surgery; neoplasms were found in 13, renal failure in eight, bacterial infections in five, liver disease in five, gastrointestinal disorders in five, and immune disease in four; two had been intravenous drug abusers; other miscellaneous disorders were observed in three. The fungal infection was limited to the myocardium in 27 patients and to the endocardium in 17 patients. Myocardium and endocardium were involved in nine patients and pericardium and myocardium in five; two patients had pericarditis alone. The most frequent organism was Candida (62 per cent). Aspergillus (12 per cent) and Phycomycetes (12 per cent) were also found frequently. In 51 patients (85 per cent) other deep organs, usually lung, kidney, brain, or spleen were involved. Cultures for fungus had been positive in 26 patients prior to death, and postmortem cultures were positive in 29 patients. Patients who had undergone cardiac surgery had a higher incidence of endocarditis (93 per cent), with Candida (53 per cent) being the most frequent cause. Patients who had received antineoplastic drugs, antibiotics, or corticosteroids had a higher incidence of myocarditis (79 per cent), again most often due to Candida (60 per cent).
Isolated infarction of the right ventricle is an extremely rare entity. A patient is described with diffuse interstitial lung disease who developed ST segment elevation in inferior and anterior leads on a routine electrocardiogram and at autopsy was found to have an isolated right ventricular infarct involving approximately 70% of the right ventricular circumference without involvement of the left ventricle and septum. This case illustrates that isolated right ventricular infarction in the presence of cor pulmonale and right ventricular hypertrophy can produce an injury current in the limb and precordial leads of the electrocardiogram which mimics that seen in typical transmural infarction of the left ventricle.
Congenital coronary artery anomalies have been associated with sudden death. Twenty-two patients who were victims of sudden death (mean age 46) and who had no significant anatomic cause of death were examined at autopsy and compared with 19 patients who died of known causes (control group). The hearts of these 41 patients were examined for abnormalities of acute angle takeoff of the coronary artery and presence of ostial valve-like ridges. Of the 22 patients who died suddenly, 13 (59%) had acute angle takeoff of the coronary artery and 9 (41%) had ostial valve-like ridges. Of the 19 control subjects, 4 (21%) had acute angle takeoff and only 2 (11%) had an ostial valve-like ridge. The difference was statistically significant (p = 0.015 and 0.031, respectively). It is suggested that aortic root dilation may compress coronary arteries with acute angle takeoff and that ostial valve-like ridges may act as occlusion valves. Thus, either may cause acute obstruction of the proximal coronary artery and lead to sudden death. A very lethal combination for sudden death would be the presence of severe coronary artery disease, an acute angle takeoff and an ostial valve-like ridge.