Myocardial disarray: an architectural disorganization linked with adrenergic stress?

BACKGROUND: Myocardial disarray is a structural abnormality found in specific zones of the normal heart. In some conditions, such as hypertrophic cardiomyopathy (HCM), its occurrence represents a pathological process leading to myocardial asynergy. The incidence of "pathological" myocardial disarray in humans is still not known. It has been suggested that a link exists between adrenergic overactivity and myocardial disarray. The aim of the present study is to compare heart findings in conditions with and without chronic sympathetic overtone for evidence of possible linkage in humans. MATERIALS AND METHODS: A total of 340 hearts were studied. They were divided into seven groups: sudden/unexpected coronary death; sudden/unexpected death in silent Chagas' disease; brain haemorrhage following berry aneurysm rupture; transplanted hearts; congestive heart failure, AIDS and cocaine abuse. Findings in these hearts were compared with anatomic changes in 92 control hearts, where the decedent had died from head trauma, electrocution, or carbon monoxide intoxication. The frequency and presence of myocardial disarray were recorded and correlated to heart weight, extent of myocardial fibrosis, and contraction band necrosis (CBN). RESULTS: Hearts from patients with conditions that increased sympathetic tone showed an association of myocardial disarray and contraction band necrosis without any relationship to heart weight. CONCLUSIONS: Myocardial disarray was observed in cardiac areas where it is not found normally. It was associated with adrenergic myocardial stress morphologically expressed by a higher number of foci (p<0.01) and myocells (p<0.001) with CBN versus findings in normal subjects. The condition deserves further study as a possible myocardial asynergic and arrhythmogenic factor especially in sudden/unexpected death.

A systematic study of a myocardial lesion: colliquative myocytolysis.

BACKGROUND: The term "myocytolysis" was first used to define the repair process of contraction band necrosis associated with an acute myocardial infarction. On the other hand, in the latter condition a "myofibrillolysis," presenting edematous myocardial cells not involved by infarct necrosis, and without evidence of repair process was reported. The objective of this study is to establish the frequency, extent and meaning of this myocardial lesion. MATERIALS AND METHODS: In 12 groups of patients for a total of 432 cases with and without coronary heart disease, "colliquative myocytolysis"--i.e., progressive vacuolization by loss of myofibrils until their total or subtotal disappearance associated with intramyocellular edema in absence of any cellular reaction--was graded in 16 histological slides of the different cardiac regions in each pathological case. RESULTS: Colliquative myocytolysis (CM) was present in more than 90% with a maximal extent in cases of irreversible congestive heart failure followed by transplanted heart cases (67%) with a survival greater than 1 week. In all other groups, the lesion was absent or minimal. CONCLUSIONS: No correlation was found between CM and contraction band necrosis, gender, age, heart weight, myocardial fibrosis, coronary artery stenosis, clinical data. Colliquative myocytolysis is a specific histological marker of congestive heart failure, without relation to coronary blood flow, heart weight and myocardial fibrosis. Vacuolization of myocardial cells may be due to other causes (e.g., storage disease, etc.) or may be an artifact. There is no support for the belief that coronary ischemia or myocardial hypoxia is its causes.

Region-of-interest cone beam computed tomography (ROI CBCT) with a high resolution CMOS detector.

Cone beam computed tomography (CBCT) systems with rotational gantries that have standard flat panel detectors (FPD) are widely used for the 3D rendering of vascular structures using Feldkamp cone beam reconstruction algorithms. One of the inherent limitations of these systems is limited resolution (<3 lp/mm). There are systems available with higher resolution but their small FOV limits them to small animal imaging only. In this work, we report on region-of-interest (ROI) CBCT with a high resolution CMOS detector (75 µm pixels, 600 µm HR-CsI) mounted with motorized detector changer on a commercial FPD-based C-arm angiography gantry (194 µm pixels, 600 µm HL-CsI). A cylindrical CT phantom and neuro stents were imaged with both detectors. For each detector a total of 209 images were acquired in a rotational protocol. The technique parameters chosen for the FPD by the imaging system were used for the CMOS detector. The anti-scatter grid was removed and the incident scatter was kept the same for both detectors with identical collimator settings. The FPD images were reconstructed for the 10 cm x10 cm FOV and the CMOS images were reconstructed for a 3.84 cm × 3.84 cm FOV. Although the reconstructed images from the CMOS detector demonstrated comparable contrast to the FPD images, the reconstructed 3D images of the neuro stent clearly showed that the CMOS detector improved delineation of smaller objects such as the stent struts (~70 µm) compared to the FPD. Further development and the potential for substantial clinical impact are suggested.

Nemaline myopathy with associated cardiomyopathy. Report of clinical and detailed autopsy findings.

We describe the clinical features and autopsy findings of an adult patient who had nemaline myopathy and an associated progressive cardiomyopathy. The spinal cord and the results of morphometric analysis of multiple peripheral nerves were normal. There was probable intrafusal fiber involvement, in addition to the typical histopathologic features of extrafusal fibers. Cardiac dysfunction was a prominent clinical and autopsy feature, but it has been infrequently recognized in this entity. Our findings suggest that there is a poor correlation between clinical and pathologic features in this disorder, and they support the need for careful cardiac evaluation of affected patients. Furthermore, the constellation of features favors a myopathic basis for the disease, in contradistinction to some previously expressed views.

Calcification in porcine xenograft valves in children.

Calcification developed in the degenerating collagen of the cusps of three porcine xenograft heart valves implanted in children for less than 4 years. The morphologic features and effects of this calcification are presented. Calcification of porcine xenografts seems to occur more frequently and at an earlier stage after insertion in children than in adults. Host factors, possibly related to calcium homeostasis, may promote calcification; hence, these valves may not be appropriate for use in children.

Morphologic findings and causes of failure in 24 explanted Ionescu-Shiley low-profile pericardial heart valves.

From 1981 to 1987 just over 608 Ionescu-Shiley low-profile bovine pericardial bioprostheses were implanted at the Toronto Hospital. Twenty-four prostheses (11 aortic and 13 mitral) were surgically explanted from 1988 to 1990 from 20 adults (10 men and 10 women). Prosthesis failure was caused by primary tissue failure in 17 valves or by other mechanisms in seven valves. Variable degrees of tissue failure were also seen in four of the seven valves from the latter group. Primary tissue failure was characterized by fluid insudation between collagen bundles, para stent post tears (alignment stitch related, 20 valves), cusp perforation with prolapse, and calcification. The earliest cusp tears occurred at 28 months. Calcification (10 of 24 cases) was minimal in seven of 10 valves (occurring primarily at the margins of the torn cusp), moderate in two, and severe in one. Tissue overgrowth (pannus) was seen in all but three prostheses. Like its predecessor, the Ionescu-Shiley standard pericardial valve, this prosthesis failed at 2 to 5 years largely due to design-related (alignment stitch) causes and tissue degeneration. Calcification was less prominent, while tissue overgrowth (pannus) was more marked.

Acquired coronary arterial aneurysms: an autopsy study of 52 patients.

In the past decade most studies of coronary arterial aneurysms have been clinical; few have focused on morphology and etiopathogenesis. The subjects of the present autopsy study were 52 patients, 5 months to 80 years of age, with coronary arterial aneurysms. Patients were divided into two groups: 38 with atherosclerotic coronary aneurysms and 14 with aneurysms secondary to inflammation. Of the 38 patients with atherosclerotic aneurysms, 20 (53 per cent) had histories of ischemic heart disease; the aneurysms were in the right coronary artery in 18 (47 per cent), the left coronary artery in 13 (35 per cent), and in the right and left coronary arteries in seven (18 per cent). Of the four major coronary arteries, the average number of severely narrowed arteries (reduction of more than 75 per cent) in cross-sectional luminal area) was 1.8/patient; aortic aneurysms were present in eight of these patients (24 per cent). Of the 14 patients with coronary aneurysms secondary to inflammation, four had histories of ischemic heart disease; 10 had histories of an influenza-like syndrome. Isolated left coronary arterial aneurysms were seen in six of these patients (43 per cent), while eight (51 per cent) had multiple right and left coronary arterial aneurysms. The average number of severely narrowed coronary arteries in this group was 1.5/patient, and only one patient had an aortic aneurysm. Therefore, patients with atherosclerotic aneurysms are more often symptomatic; they have increased heart weights and equal numbers of coronary arterial aneurysms in the right and left vessels, and the majority (89 per cent) have single aneurysms with thrombi in the lumen. Patients with coronary arterial aneurysms secondary to inflammation are younger; the majority of these patients have a prodromal influenza-like syndrome, a low incidence of ischemic heart disease, and multiple coronary arterial aneurysms.

The pattern of desmin filaments in myocardial disarray.

"Myofiber disarray" defines a nonparallel arrangement of cardiac myocytes. The presence of a sufficient quantity of myocardial fibers showing this change is considered to be a specific histological feature of hypertrophic cardiomyopathy (HCM). However, small zones of myofiber disarray are found in both cardiac hypertrophy and other pathological conditions. Recently, we demonstrated an altered pattern of desmin intermediate filaments in disarrayed myofibers from specimens of HCM. To test the hypothesis that desmin alterations might be specific for cardiomyopathy, we performed an immunohistochemical study on myocardial surgical samples from 11 patients with HCM and from 12 patients with tetralogy of Fallot (toF) on 14 endomyocardial biopsy specimens (EMBs) from transplant recipients with myofiber disarray surrounding areas of scarring (previous biopsy site) and on specimens of four autoptic hearts with severe acquired left ventricular hypertrophy. Disarrayed myofibers from all specimens of HCM showed the following abnormalities in the pattern of desmin intermediate filament distribution: (1) decrease or loss of labeling of intercalated discs and Z bands, (2) longitudinal arrangement of desmin intermediate filaments, and (3) intense, granular staining of several myocytes. This spectrum of desmin alterations was never observed in disarrayed myofibers in specimens of toF or acquired myocardial hypertrophy or in EMBs. Altered distribution of desmin intermediate filaments seems to be specific to myofiber disarray in HCM and it may play a role in the altered myocyte arrangement in HCM.

The morphology of the human newborn ductus arteriosus: a reappraisal of its structure and closure with special reference to prostaglandin E1 therapy.

The ductus arteriosus was examined in 103 fetuses and infants to define the normal structure, development, and morphologic features of the functional and anatomic phases of ductal closure. New contributions include ultrastructural observations and the light microscopic definition of the junctional regions of the ductus with the pulmonary artery and aorta. Observations relating to ductal closure include hyperemia of the ductal vasa vasorum, the presence of longitudinal muscle bands in the inner media, necrosis of the inner ductal wall, and organization of intraluminal thrombi. We found that a ductus arteriosus that fails to close normally is liable to show morphologic lesions, including intimal fibrinous deposits, medial hemorrhages, and dissecting aneurysms. The findings were used comparatively to investigate whether prostaglandin E1 infusion, given to maintain ductal patency in 7 infants with ductus dependent congenital heart disease, was associated with specific morphologic features. We could not delineate specific changes attributable to its use.

Morphologic and morphometric analyses of muscle in the neonatal myotonic dystrophy syndrome.

Autopsy studies of three premature siblings who died soon after birth with the neonatal myotonic dystrophy syndrome revealed pulmonary hypoplasia and congenital pleural effusions. Neither of these findings has been described previously in this condition. New ultrastructural findings include focal diaphragmatic myofiber degeneration and necrosis, which were attributed to over-stretching of the fetal diaphragm. In addition, abnormally small stores of free and intravesicular glycogen were observed in skeletal muscle fibers. The morphometric features of control fetal and neonatal skeletal muscle were recorded for comparison with muscle fiber measurements in the three infants. Fiber diameters in the latter were much smaller than expected for body weights. The morphologic and morphometric findings support the concept that fetal muscle maturation is severely retarded in this syndrome.

Malignant hyperthermia susceptibility. A light and electron microscopic study of endomyocardial biopsy specimens from nine patients.

Cardiomyopathy develops in some individuals who have a susceptibility to malignant hyperthermia. We studied right ventricular endomyocardial biopsy specimens from nine patients defined as having this disorder because of positive caffeine contracture tests on skeletal muscle biopsy specimens. Three patients had clinical evidence of cardiomyopathy and six did not. Light microscopy showed cytoplasmic contraction bands, perinuclear clearing, and a mild to moderate variation in myocyte and nuclear size. Ultrastructurally cytoplasmic contraction bands were associated with cardiac villi, myofiberlysis, and myofibrillolysis. These changes and occasional breaks in the sarcolemma were regarded as artefacts of the biopsy procedure. Megamitochondriosis with accompanying degenerative changes in the mitochondria were also seen and probably indicate increased cell metabolism; vacuolation of the cytoplasm was regarded as an "aging" phenomenon. Thus, the biopsy specimens were abnormal, but the changes were artefactual or nonspecific and were not unique to this group of patients. Biopsy did not provide a morphological explanation for abnormal cardiac function.

Wear in Björk-Shiley heart valve prostheses recovered at necropsy or operation.

Thirteen Björk-Shiley prostheses, in situ for up to 27 months, were examined for wear. The discs showed "burnish marks" which did not erode the surface or "wear marks" which did. The metal cages were worn on the "arms" of the inlet strut or at the "hook" of the outlet strut, with metal wear presenting as scored areas or as beveling. This wear is minor and comparable to that seen following accelerated cycle testing in vitro. It is unlikely to seriously affect prosthesis function in the normal lifetime of an individual, but metal wear might cause disc flutter and change auscultatory findings associated with a prosthesis.

Late strut fracture of the Beall model 105 disc valve prosthesis.

Strut fracture, with embolization of the disc occluder, caused the death of a 64-year-old man who had a Beall model 105 heart valve prosthesis in the mitral position for 13 years. Scanning electron microscopy of the fractured surface revealed evidence of a fatigue failure mechanism in the metal wire. The case is unique in that strut fractures affecting this prosthesis had only been observed previously in the range of 141 to 342 days after implantation. Morphological changes in this valve prompted reexamination of three other model 105 prostheses that had been recovered from the mitral area at necropsy or surgery 9 to 10 years after insertion in 1972 or 1973. All had been kept in dry storage. The three prostheses and the valve described above showed previously unrecognized cracks in the pyrolytic carbon coating of the struts, which form the cage that limits occluder movement. The defects were located at or near the base of struts, where they entered the sewing ring and were bent to pass into the strut supporting ring. We believe that the cracks in the carbon coating precede total strut fracture and postulate that they are needed for the metal wire to be subject to a fatigue failure mechanism.

The porous-surfaced electrode: a new concept in pacemaker lead design.

Three major problems which may be encountered with endocardial pacemaker electrodes are a lack of stable position, a chronic increase in stimulation threshold, and a diminishing magnitude of the sensed endocardial signal. These problems are particularly manifest in the atrium. Having previously shown that porous metal surfaces can support stable tissue ingrowth in both bloodstream and soft tissue environments, we set out todetermine the performance of porous-surfaced endocardial pacing electrodes in the atrial position. In two groups of six dogs each, J-shaped atrial leads with Elgiloy electrode tips (2.3 mm. in diameter, 2.3 mm. in length), having either conventional smooth surfaces (control) or porous surfaces (20 to 50 micron particle size) produced by powder metallurgy techniques, were positioned in the right atrial a-pendage. Stimulation thresholds and P-wave amplitude were repeatedly measured until the dogs were put to death 30 w-eks following implantation. The presence or absence of electrode fixation was observed and the atrial tissue reaction was examined grossly and by both light and scanning electron microscopy (SEM). The porous-surfaced electrodes demonstrated superior long-term stimulation thresholds which, at 30 weeks, averaged less then one third of those in the control group. In addition, the porous group showed a small but significant improvement in the amplitude of the sensed P wave. None of the smooth-surfaced electrodes showed fixation, and the tissue reaction consisted of a thick layer of granulation and fibrous tissue on the underlying endocardium, widely separating the electrode from the myocardium. In contrast, all of the porous-surfaced electrodes were fexed to the endocardium by fibrous tissue ingrowth into the surface pores. This tissue fixation of the electrode tip in close proximity to underlying myocytes explains their superior performance.

Ischemic contracture of the left ventricle. Production and prevention.

Ischemic contracture of the left ventricle ("stone heart") is a recognized complication of prolonged periods of interruption of the coronary circulation during open-heart surgery. We have examined the effects of moderate hypothermia (28 degrees C.) and preoperative beta-adrenergic blockade (propranolol, 0.5 mg. per kilogram; 1.0 mg. per kilogram) on contracture development during ischemic arrest of the heart. Four groups of 8 dogs each were placed on total cardiopulmonary bypass, and ischemic arrest of the heart was produced by cross-clamping the ascending aorta and venting the left ventricle. Intramyocardial carbon dioxide tension was continuously monitored by mass spectrometry. When anaerobic energy production ceased, as indicated by a final plateau in the intramyocardial carbon dioxide accumulation curve, the ischemic arrest was terminated and the contractile state of the heart observed. These results are given in the text. We conclude that beta-adrenergic blockade delays, but does not prevent, the onset of ischemic contracture of the left ventricle under normothermic conditions. Moderate hypothermia appears to prevent this complication completely.

Type and extent of myocardial injury related to brain damage and its significance in heart transplantation: a morphometric study.

BACKGROUND: Focal myocardial necrosis reported in patients who died of brain lesions and in donor hearts soon after insertion has been attributed to catecholamine-related injury induced before operation, or in the perioperative period. Interpretation of the morphofunctional type of myocardial injury observed and its quantification may help understand both its pathophysiology and clinical relevance. METHODS: In 27 patients without heart disease who died of intracranial brain hemorrhage after berry aneurysm rupture, terminal clinical signs were correlated with the presence of absence of myocardial injury. All hearts were systematically examined, and the total histologic area was measured in square millimeters, with both the number of foci and myocardial cells showing necrosis, normalized to 100 mm2. Forty-five cases of fatal head trauma (26 "instantaneous" and 19 "rapid" deaths) in normal subjects and 38 cases of acquired immunodeficiency syndrome with (14 cases) or without (24 cases) severe brain damage were used as control subjects. RESULTS: Contraction band necrosis was the only form of myocardial necrosis found in 89% of patients with acute brain hemorrhage. Its extent was 26 +/- 34 foci and 67 +/- 104 necrotic myocardial cells x 100 mm2. In patients with acquired immunodeficiency syndrome, its frequency was 58% in those without and 78.5% with severe brain lesions, with foci and myocardial cell values of 1 +/- 1.5 and 10 +/- 22 and 7 +/- 16 and 17 +/- 32, respectively. In head trauma cases with instantaneous death, the frequency was 4% (one case only with foci 0.5 and myocardial cells 35), whereas with a rapid death it was 40% (foci 12 +/- 18 and myocardial cells 21 +/- 33). CONCLUSIONS: The observed myocardial injury was present in all groups examined, being maximal in patients with intracranial brain hemorrhage with longer survival and minimal in patients with head trauma who died instantaneously. In this setting, this lesion is typical of catecholamine myotoxicity and may express a sympathetic overstimulation either in the agonal period and independent of therapy or be caused by brain injury, especially intracranial brain hemorrhage. However, the extent of myocardial injury observed was minimal and should not jeopardize cardiac function if hearts from such subjects are transplanted.

The healed and sealed aortic intimomedial tear.

A retrospective study of surgical pathology and autopsy material revealed eight examples of intimomedial tears that had healed with the tear sealed or obliterated by fibromuscular tissue; four were the result of iatrogenic trauma related to application of aortic cross clamps during surgery and four developed spontaneously. The former were single lesions, the latter all associated with other intimomedial tears. Iatrogenic/traumatic tears occurred in ascending aortas that had histologically normal medias, spontaneous ones were located at sites where intimal tears are found and affected aortas with diseased medias. Observations in these cases suggest a triphasic process in the pathogenesis of dissecting aneurysms involving an intimal tear, hemorrhage into the resultant defect, and a hemorrhagic dissection of the media. These processes do not necessarily follow in sequence so the mechanism of each must be understood. The size and morphology of healed and sealed intimomedial tears indicate some might be detectable by ultrasonography and/or other imaging techniques. They seem uncommon but could be missed by both imagers and pathologists.

Autonomic and myocardial changes in middle cerebral artery occlusion: stroke models in the rat.

Stroke models in larger animals such as the cat, dog and monkey are becoming increasingly more expensive and less readily available. However, the rat is an excellent model for focal cerebral ischemia. Rats are readily available, inexpensive and their neuroanatomy and brain function have been studied extensively. Increases in plasma catecholamines and myocardial damage have been observed in clinical stroke. We examined autonomic and myocardial changes in two rat stroke models. In one model only the middle cerebral artery was occluded (MCAO) while the other model involved occlusion of both the MCA and the common carotid artery (MCAO/CCAO). Arterial blood pressure and heart rate were monitored continuously in 25 male rats (326-430 g) that underwent one of the following procedures: (1) MCAO only; (2) MCAO/CCAO; (3) CCAO only; and (4) sham occlusions (SHAM). Arterial blood samples (0.5 ml) for radioenzymatic assay of norepinephrine (NE) and epinephrine (E) were taken twice before the occlusions and at 90 and 180 min after the occlusions. The animals were perfused at the end of the experiment and the heart removed and examined histologically. Tetrazolium salts were reacted with oxidative enzymes to delineate the region of inadequate perfusion. The mean blood pressure and pulse pressure of the SHAM, MCAO/CCAO and CCAO groups significantly declined from initial values (from an average of 78 to 53 mm Hg) during the course of the experiment. However, the mean blood pressure and pulse pressure of the MCAO rats did not change during the experiment, so that the final mean blood pressure and pulse pressure were significantly higher than in the other 3 groups. The levels of both NE and E increased significantly (NE, 1443 +/- 285.9 to 4095 +/- 929 pg/ml; E, 2402 +/- 623 to 3741 +/- 1166 pg/ml) following occlusion in the MCAO group only while the other 3 groups did not change. Four of 6 hearts in the MCAO group were abnormal, showing evidence of subendocardial hemorrhage, ischemic damage or subendocardial congestion. MCAO also resulted in a consistent region of the brain with inadequate perfusion including the insular cortex. These autonomic and myocardial changes appear to mimic some of the changes seen clinically in stroke patients and provide the first acute stroke model for studying autonomic dysfunction in the rat.

A method for including redundant data in computed tomography.

A method for including redundant data in fan-beam computed tomography (CT) is presented. It is a natural extension of the Parker [Med. Phys. 9, 254-257 (1982)] short-scan approach applied to divergent fan-beam (or cone-beam) data when the data set covers between the minimally complete set of 180 degrees plus fan angle and 360 degrees. A virtual fan angle is introduced whose value is the difference between the angular range of the data collected and 180 degrees. Parker-weights are then applied as if the field-of-view is spanned by the virtual fan angle.

Coexistence of Fabry's disease and systemic lupus erythematosus.

This report describes a case of a female with systemic lupus erythematosus, who was subsequently diagnosed with Fabry's disease. Due to similarities in the organs involved by these two multisystem disorders, difficulties were encountered in establishing a prompt diagnosis of Fabry's disease. That and subsequent management of this patient are discussed. A literature review of the coexistence of the two disorders along with the potential pathogenic mechanisms explaining this association are explored.