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.

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.

Markers of cardiac oxidative stress and altered morphology after intraperitoneal cocaine injection in a rat model.

This study was designed to assess the parameters of myocardial oxidative stress and related cardiac morphological changes following intraperitoneal cocaine exposure in rats. The cardiac levels of reduced glutathione(GSH), oxidised glutathione(GSSG), ascorbic acid (AA), and the production of malondialdehyde (MDA) were measured, as well as the variations of activity in the enzyme systems involved in cell antioxidant defence, glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). After chronic cocaine administration for 30 days GSH was significantly depleted in the heart from 30 min (P < 0.001) to 24 h (P < 0.001) after exposure, and GSSG was increased for a similar time (P < 0.05 at 30 min and P < 0.01 at 24 h). SOD increased during the first hour (P < 0.001), GR and GSH-Px both increased from 30 min to 24 h, and these increases were statistically significant (P < 0.01 and P < 0.001 at 30 min and P < 0.01 and P < 0.001 at 24 h, respectively). The AA levels increased after 1 h (P < 0.01), remaining significantly so for 24 h (P < 0.001) and MDA increased from 30 min to 24 h, all values being highly significant (P < 0.001). The body weight was significantly (P < 0.001) reduced in both cocaine groups (40 mg/kg x 30 days and 40 mg/kg x 10 days + 60 mg/kg x 20 days). The heart weight (P < 0.01) and its percentage of the body weight (P < 0.001) were significantly higher in these two groups than in the controls. Similarly, in the noradrenaline 4 mg/ kg x 30 days group, the body weight was significantly (P < 0.001) reduced and the heart weight (P < 0.01) and its percentage of body weight (P < 0.001) were significantly higher than in the controls. In comparing the cocaine and noradrenaline experiments, the frequency and extent of cardiac lesions obtained with 40 mg/kg x 10 days + 60 mg/kg x 20 days of cocaine were similar to those with 8 mg/kg of noradrenaline at 24 h. In this experimental model, cocaine administration compromised the antioxidant defence system of the heart associated with a significant increase of heart weight and the percentage of body weight.

Anabolic steroid abuse and cardiac sudden death: a pathologic study.

CONTEXT: Androgenic anabolic steroids (AAS) used for improving physical performance have been considered responsible for acute myocardial infarction and sudden cardiac death. OBJECTIVE: To establish the relationship between AAS and cardiac death. DESIGN: Case report. PATIENTS: Two young, healthy, male bodybuilders using AAS. MAIN OUTCOME MEASURES: Pathologic cardiac findings associated with AAS ingestion. RESULTS: The autopsy revealed normal coronary arteries. In one case, we documented a typical infarct with a histologic age of 2 weeks. A segmentation of myocardial cells at the intercalated disc level was observed in the noninfarcted region. This segmentation was the only anomaly detected in the second case. No other pathologic findings in the heart or other organs were found. Urine in both subjects contained the metabolites of nortestosterone and stanozolol. COMMENT: A myocardial infarct without vascular lesions is rare. To our knowledge, its association with AAS use, bodybuilding, or both lacks any evidence of a cause-effect relationship. The histologic findings in our 2 cases and in the few others reported in medical literature are nonspecific and do not prove the cardiac toxicity of AAS. A better understanding of AAS action on the neurogenic control of the cardiac function in relation to regional myocardial contraction and vascular regulation is required.

Myocardial contraction bands. Definition, quantification and significance in forensic pathology.

Pathological contraction bands affecting myocardial cells are observed in many different human conditions and in different experimental models. Their morphology was defined long ago but we need to understand the pathogenesis and functional meaning. A distinction between different histological forms of contraction bands and their quantification in a large spectrum of human diseases (262 cases) and a normal population sample where death was due to various types of accidental death (170 cases) produced the following conclusions: 1) The term "contraction band necrosis", as used presently, is ambiguous and should be reserved for a specific morpho-functional entity induced experimentally by intravenous catecholamine infusion and seen in equivalent human cases with pheochromocytoma. 2) In human pathology it may represent a sign of adrenergic stress linked with malignant arrhythmia/ventricular fibrillation. 3) Beyond a histological threshold of 37+/-7 foci and 322+/-99 myocells/100 mm2, the lesion may indicate sympathetic overdrive in the natural history of a disease and associated arrhythmogenic supersensitivity. 4) The detection of few pathological contraction bands in normal subjects in some types of accidental death correlates with the survival time, suggesting an agonal adrenergic stimulation to promote the cardiac pump.

Myocardial findings in fatal carbon monoxide poisoning: a human and experimental morphometric study.

The aim of this study was to define the status of the myocardium in selected human cases of acute, fatal carbon monoxide intoxication and the myocardial changes in rats exposed to carbon monoxide in relation to the type of cardiac arrest and the effects of reoxygenation following pre-fatal CO intoxication. The human study consisted of 26 cases (17 accidental and 9 suicide) of acute, fatal CO intoxication, without evidence of obstructive coronary atherosclerosis or history of ischemic heart disease which were compared with 45 cases of fatal head trauma in subjects who died instantaneously (26 cases) or within 1-12 h (19 cases). Inhalation of a lethal dose of CO in rats was compared with sub-lethal doses plus reoxygenation with and without pre-treatment by a betablocker. In all human and experimental histological sections, changes were normalised per mm2 area. In the human cases the myocardium did not show any ischemic types of changes or other lesions. Only in "three accidental" cases a few, small foci of coagulative myocytolysis were detected. In the case of spontaneous death in 31 rats following CO intoxication, no pathological myocardial changes were seen. Of the 15 "reoxygenated" rats, 2 of the 7 spontaneous deaths presented coagulative myocytolysis with 15 +/- 6 foci and 381 +/- 255 necrotic myocells. All the eight rats sacrificed at 3 h had coagulative myocytolysis with 5 +/- 4 foci and 60 +/- 47 myocells. Of the 24 reoxygenated rats pre-treated with a betablocker, 5 died spontaneously after a short survival and 2 of these showed 11 +/- 9 foci and 21 +/- 20 myocells. The 19 rats sacrificed after 3 h all presented coagulative myocytolysis with figures of 75 +/- 43 and 356 +/- 301 with 0.5 mg/kg of propranolol hydrochloride and 55 +/- 45 and 253 +/- 216 with 2 mg/kg, respectively.

[What I have learned by monitoring my own ischemia]. / Cosa ho imoarato monitorando la mia ischemia.

Twenty years ago, I became an "unstable patient", starting with a short episode of precordial discomfort and tiredness, ischemic ECG without enzymes, hypokinetic apex and no other signs. Following a week in bed and a lot of sleep, I went back to my usual lifestyle, refusing to undergo cineangiography or any hydraulic intervention. For ten years, the periodic controls showed no changes and I continued my intense activity under adequate therapy until another more severe episode occurred. Again, during a stressful and psychologically negative period, I experienced more severe precordial discomfort that was accentuated after minor psychological tension, whereas long and intense physical exercise was instead asymptomatic. The hypokinetic area was more extensive--no enzymes again--with a more severe ischemic ECG. My inability to face my psychological stress suggested surgical bypass, given the fact that since the Fifties, any type of intervention--even if nothing is vascularized--would nevertheless block pain and allow me to return to a normal lifestyle (denervation). At that time, cineangiography showed the occlusion of all three main coronary arteries. These occlusions had been there for years without an infarct and were obviously already compensated by adequate collateral circulation, as demonstrated by the normal lifestyle I had led with intense and long-lasting physical exercise. I returned to my regular activity, again mainly under anti-adrenergic stress therapy, and now, another ten years after surgery, I am still waiting for a third episode or something else. What have I learned from studying myself? I've learned that every ischemic patient has his own history and must learn how to face his own risks, the different patterns of so-called ischemic heart disease can not be theorized in a unique etiopathogenesis, the adrenergic system plays a major role in this disease, the "plumbing" vision is supported by reasons which have little to do with the knowledge--as yet incomplete--of the natural history of this disease, and the data obtained in years of research have been confirmed.

Coronary artery aneurysms in a young adult: a case of sudden death. A late sequelae of Kawasaki disease?

The case concerns the sudden death of a 21-year-old male during a soccer game. The autopsy revealed large, calcified saccular aneurysms at the origins of both the left anterior descending and the right coronary arteries. Histologically, the wall of the aneurysms was thin and composed of an internal fibro-calcified layer and an external thin tunica media. There was no evidence of active inflammation. The autopsy findings and a detailed medical history support the diagnosis of a late fatal sequela of Kawasaki disease.

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.

Sudden and unexpected death in clinically 'silent' Chagas' disease. A hypothesis.

BACKGROUND: Chagas' heart disease presents an interesting model of cardiac autonomic nerve dysfunction associated with morphologic lesions. A lack of quantitative evaluation of the latter suggested this study in which hearts from 34 subjects who were serum-positive for Chagas' disease but had no clinical evidence of it and who died suddenly and unexpectedly, out-of-hospital, were examined. METHODS AND RESULTS: By systematic myocardial sampling the histologic area was measured to establish: (a) the number of focal lymphocytic infiltrates x 100 mm2 and average number of lymphocytes per focus; (b) number of foci of, and myocells with, coagulative myocytolysis (contraction band necrosis) x 100 mm2; and (c) the percentage of substitutive myocardial fibrosis. In all cases findings were: (a) intermyocellular lymphocytic infiltrates (6 +/- 6 foci x 100 mm2); (b) coagulative myocytolysis (3 +/- 5 foci and 26 +/- 56 myocells x 100 mm2). CONCLUSIONS: In all 34 subjects quantitative analysis showed extensive lymphocytic infiltrates and myocardial damage typical of catecholamine cardiotoxicity. These two acute or active histological changes may explain their sudden demise produced by focal denervation with regional asynergy and consequent compensatory adrenergic stimulus with myotoxicity and malignant arrhythmia.

Myocardial necrosis and cocaine. A quantitative morphologic study in 26 cocaine-associated deaths.

A quantification of different forms of acute myocardial necrosis, myocardial leukocytic infiltrates and myocardial fibrosis was accomplished in 26 chronic cocaine abusers who died of cocaine intoxication and compared to 45 normal subjects who died from head trauma and 38 who died of acquired immunodeficiency syndrome. The findings were: absence of infarct necrosis, a similar frequency and extent of coagulative myocytolysis (contraction band necrosis) and leukocytic infiltrates in cocaine abusers and normal controls, and an absence of myocardial fibrosis in cocaine abusers. These findings question both the acute and chronic cardiotoxicity of cocaine. The infarct-like pattern in some predisposed subjects may be due to an excess of catecholamine release induced by the drug resulting in coagulative myocytolysis and platelet thrombi.

Lipomatous metaplasia in left ventricular scar.

BACKGROUND AND OBJECTIVE: Substitution of interstitial tissue by fat may be observed in the right ventricle of hearts but is less common in the left ventricle. Fat was noted in myocardial scars of patients undergoing heart transplantation, prompting this retrospective study to determine the frequency of left ventricular myocardial scar being replaced by fat and its significance METHODS AND RESULTS: The left and right ventricles and coronary arteries were sampled systematically and lesions quantified histologically in 97 normal subjects dying accidentally; 116 consecutive failing hearts excised at transplantation from patients with ischemic heart disease, idiopathic dilated cardiomyopathy or chronic valvulopathy; and 34 autopsy hearts of apparently normal subjects with "silent' Chagas' heart disease who died suddenly and unexpectedly. Twenty-two left ventricular aneurysmectomy specimens from ischemic patients with heart failure were also studied. Among excised hearts lipomatous metaplasia of myocardial scar was observed in 68% of ischemic heart disease, in 37% of chronic valvulopathy and in 26% of idiopathic dilated cardiomyopathy patients; it was seen in 15% of Chagasic patients and in 55% of aneurysm walls. CONCLUSIONS: Lipomatous metaplasia of scar is often associated with severe heart failure and is more frequent and extensive in ischemic heart disease. Transformation of a compact scar into compressible and "sliding' adipose tissue may worsen ventricular wall function, thus facilitating and/or aggravating aneurysm formation. This phenomenon must be considered in the evaluation of myocardial repair, cardiac imaging of viable myocardium, quantitative morphology of autopsy specimens, and qualitative and quantitative biochemical analysis of myocardial tissue.