Coagulative Myocytolysis Research Articles

Colloid cyst of the third ventricle, hypothalamus, and heart: a dangerous link for sudden death

Colloid cysts are rare congenital, intracranial neoplasms, commonly located in the third ventricle. Colloid cysts are endodermal congenital malformations. The cysts commonly range in size from 1–2 cm in diameter, although large cysts >3 cm in size have been reported. The components of the cyst include an outer fibrous capsule over an inner epithelium. The epithelium is usually a single layer of mucin-producing or ciliated cells. Such cysts contain mucoid and gelatinous material, which is positive for both Periodic acid Schiff (PAS) and mucicarmen staining. Although colloid cysts usually represent histopathologically benign neoplasms, they can result in sudden, unexpected and potentially lethal complications. The mechanism(s) of death is still a controversial subject and several mechanisms have been postulated to explain the sudden onset of severe symptoms and of fatal rapid deterioration in patients with colloid cysts. In this case, macroscopic and histological findings addressed the diagnosis of colloid cyst of the third ventricle with diffuse myocardial injury (coagulative myocytolysis or contraction band necrosis, CBN) and led us to conclude that acute cardiac arrest due to hypothalamus stimulation in the context of colloid cyst of the third ventricle was the cause of death. As the hypothalamic structures which are involved in neuroendocrine and autonomic regulation playing a key role in cardiovascular control are located close to the walls of the third ventricle which is the most frequent anatomical site of colloid cyst, this may suggest that reflex cardiac effects due to the compression of the hypothalamic cardiovascular regulatory centers by the cyst explain the sudden death in patients harboring a colloid cyst when signs of hydrocephalus or brain herniation are lacking.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4915842848034158

Sudden Infant Death in an 8-Month-Old Baby With Dengue Virus Infection

Sudden infant death due to dengue virus infection is very rare. An 8-month-old male infant was found unresponsive during a nap in his nursery school. We emphasize the usefulness of dengue viral antigens as a postmortem diagnostic technique to demonstrate the presence of virus in human tissue specimens by immunohistochemistry and Western blotting.

Early cardiac damage after subarachnoid hemorrhage in rats

Detection of the myocardial damage in the early stage of subarachnoid hemorrhage (SAH) is impossible without a good animal model. We investigated the feasibility of using immunohistochemical cardiac troponin I (cTnI) staining to detect the early myocardial damage in rats subject to SAH by endovascular perforation. SAH induced increases in mean blood pressure, heart rate, intracranial pressure, plasma norepinephrine and cTnI accompanied with electrocardiogram abnormalities. The heart was dilated. The myocardium revealed coagulative myocytolysis and remarkable loss of myocardial tissue cTnI in myocytolytic areas within 3 h after SAH. Thus, we create a rat SAH model that can be applied in studying the mechanisms of the early myocardial damage following SAH and for evaluating therapeutic strategies in SAH patients.

Comparison of Heart Failure in Children with Enterovirus 71 Rhombencephalitis and Cats with Norepinephrine Cardiotoxicity

The mechanism of heart failure in patients with enterovirus 71 rhombencephalitis (brain stem encephalitis) remains unknown. Our previous reports hypothesized that a catecholamine storm induced by rhombencephalitis may account for the heart failure. The aim of this study was to develop a novel feline model of norepinephrine cardiotoxicity and compare the resulting heart failure to that in children with enterovirus 71 rhombencephalitis. Nine of 75 children (12%) with enterovirus 71 rhombencephalitis (5 boys and 4 girls; age, 4-28 months; median age, 16 months) were complicated with left ventricular hypokinesia (ejection fraction, 31 +/- 9%). Six cats (weight, 3.03 +/- 0.64 kg) were administered intravenous norepinephrine 30 microg/kg/min for 3 hours. Echocardiography assessed the left ventricular diameter and function before and after the administration of norepinephrine. Pathology studies included hematoxylin and eosin stain and in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end-labeling assay. In the feline model, norepinephrine induced significant left ventricular dilatation (end diastolic diameter from 1.18 +/- 0.19 to 1.62 +/- 0.22 cm, p = 0.001; endsystolic diameter from 0.54 +/- 0.09 to 1.36 +/- 0.32 cm, p = < 0.001) and hypokinesia (ejection fraction from 87.5 +/- 4.1 to 35.2 +/- 16.3%, p = 0.001). Heart specimens from 4 patients and six cats showed similar pathology findings, including myocardial hemorrhage, cardiomyocyte apoptosis, and coagulative myocytolysis, which is characterized by sarcoplasmic coagulation, granulation, vacuolization, myofibrillar waving, and disruption. Both groups showed no significant inflammatory reaction. In conclusion, heart failure in patients with enterovirus 71 rhombencephalitis is similar to that in cats with norepinephrine cardiotoxicity. Norepinephrine cardiotoxicity may play a role in the pathogenesis of heart failure in enterovirus 71 rhombencephalitis.

Sympathetic activity and myocardial damage after stimulation of dorsal medulla and vagotomy in a novel animal model

Many kinds of brain lesions cause sympathetic hyperexcitation and myocardial damage. A novel animal model was developed for the correlation of sympathetic excitation with ventricular dysfunction and myocardial damage. Six cats (3.23±0.26 kg) under intraperitoneal urethane-chloralose anesthesia were artificially ventilated and bilaterally vagotomized. They underwent an electrical stimulation of unilateral dorsal medulla for 180 min (monopolar square-wave pulses, 10 Hz, 10 V, 0.5 ms). Mean blood pressure, heart rate plasma concentration of norepinephrine and left ventricular size and ejection fraction were measured at 0, 5, 15, 30, 60, 90, 120 and 180 min. Mean blood pressure (mm Hg), heart rate (beats/min) and norepinephrine (pg/ml) increased abruptly from 128±15, 203±22 and 353±123 to 234±26, 240±13 and 4727±2159 at 5 min after electrical stimulation (all p<0.01). The left ventricles showed significant dilatation (end-diastolic diameter: from 1.35±0.13 to 1.84±0.21 cm, p=0.006; end-systolic diameter: from 0.65±0.20 to 1.54±0.24 cm, p=0.002) and hypokinesia (ejection fraction: from 88.9±6.4% to 37.3±8.7%, p<0.001). Cardiac pathology revealed myocardial hemorrhage, cardiomyocyte apoptosis and coagulative myocytolysis (contraction band necrosis), characterized by sarcoplasmic coagulation, granulation and disruption. In conclusions, the present experiment develops a novel animal model in which stimulation of the pressor area in the dorsal medulla in vagotomized cats produces sympathetic hyperexcitation accompanied with myocardial dysfunction and damage. This model may be applicable for studying protective effect of drugs on myocardial dysfunction and damage caused by sympathetic hyperexcitation occurring in brain diseases.

Cardiac complications of enterovirus rhombencephalitis

Background: Epidemics of enterovirus 71 infection have caused the death of many children throughout the world. Rhombencephalitis, brain stem encephalitis, and heart failure were present in all of the fatal...

Myocardial necrosis after envenomation by the scorpion Tityus serrulatus

A 4 years old boy died a few hours after he had been stung by a scorpion ( Tityus serrulatus). At necropsy, there were multiple foci of coagulative myocytolysis in the myocardium and pulmonary oedema. Myocardial necrosis was probably associated with the sympathetic storm induced by scorpion envenomation, and may have contributed to cardiac failure and death.

A case of total atrial septal defect detectedwith coagulative myocytolysis in the atrium

A case of total atrial septal defect detectedwith coagulative myocytolysis in the atrium

Sequential changes in localization of repair-related proteins (heat shock protein 70, ubiquitin and vascular endothelial growth factor) in the different stages of myocardial infarction.

The myocardium expresses vascular endothelial growth factor (VEGF), heat shock protein 70 (HSP70), and ubiquitin immediately after the onset of cardiac ischaemia. This study demonstrated the sequential changes in localization of these proteins, in addition to fibronectin and troponin T (TnT), in human hearts with myocardial infarction (MI). Myocardial tissues from 40 autopsied MI cases were immunostained with the five antibodies against VEGF, HSP70, ubiquitin, fibronectin and TnT. Fibronectin was recognized only in the cardiomyocytes with infarction. Although TnT, HSP70, ubiquitin and VEGF were detected in the affected myocardium in the early stages, their expression in cardiomyocytes around infarcted foci were more intense. The cardiomyocytes with coagulative myocytolysis were positive for fibronectin, but negative or weakly positive for TnT, HSP70, ubiquitin and VEGF. In contrast, the cardiomyocytes with colliquative myocytolysis were strongly positive for TnT, HSP70, ubiquitin and VEGF, but negative for fibronectin. Immunostaining using antibodies to fibronectin, TnT, HSP70, ubiquitin and VEGF is useful for the discrimination between infarcted myocytes and ischaemia-damaged myocytes in the human heart with MI at autopsy.

Acute myocarditis following Tityus trinitatis envenoming: morphological and pathophysiological characteristics

The clinicopathological features of four cases of scorpion envenoming by Tityus trinitatis are presented. The cardiac histopathology is recorded in the two fatal cases. The pathology of the acute myocarditis was a mixed picture of a toxic myocarditis and coagulative myocytolysis. These cardiac lesions are also seen in catecholamine induced cardiotoxicity and lend support to the theory that an adrenergic surge follows scorpion envenoming. A brief review of scorpion envenoming syndrome is undertaken in the light of these findings.

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.

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×100 mm 2 and average number of lymphocytes per focus; (b) number of foci of, and myocells with, coagulative myocytolysis (contraction band necrosis) ×100 mm 2; and (c) the percentage of substitutive myocardial fibrosis. In all cases findings were: (a) intermyocellular lymphocytic infiltrates (6±6 foci×100 mm 2); (b) coagulative myocytolysis (3±5 foci and 26±56 myocells×100 mm 2). 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.

Histomorphogenesis of soman-induced encephalocardiomyopathy in Sprague-Dawley rats.

Although myocardial damage caused by soman has been previously reported, its relation to brain damage is unclear. In order to clarify this relationship, we examined the histomorphogenesis of central nervous system (CNS) and myocardial lesions in Sprague-Dawley rats, given atropine methylnitrate (20 mg/kg) and HI-6 (125 mg/kg) ip 10 min before a single injection of 0 or 130 micrograms soman/kg (sc) and sacrificed 45 min and 1.5 hr, 3 hr, 24 hr, and 72 hr later. Bilaterally symmetrical CNS damage began with vacuolation of the neuropil and was followed by astrocytic degeneration and neuronal necrosis culminating in liquefaction necrosis and focal hemorrhage. The cerebral cortex, limbic system, thalamus, and substantia nigra were common target sites. Repair in affected sites was characterized by capillary endothelial cell proliferation, microgliosis, and reversal of microvacuolation. Myocardial damage began with myocytolysis and contraction bands and evolved into coagulative myocytolysis and replacement fibrosis with a transient recruitment of acute inflammatory cells. The left ventricle, especially its free wall and papillary muscles, was consistently affected. There was good correlation among seizures, CNS damage, and myocardial lesions at all times following treatment. The results support the view that CNS lesions are associated with protracted seizure activity and provide evidence that myocardial damage is neurogenic.

Characterization of Transmural and Subendocardial Infarction by Typing and Grading of Ischemic Lesions in Autopsied Human Hearts

Two types of myocardial infarction, transmural and subendocardial, were macroscopically examined, and the gross and microscopic findings were correlated. The transmural type usually consisted of yellowish-brown coagulation necrosis in the center of an infarcted focus and coagulative myocytolysis at the marginal zone. The subendocardial type was characterized by coagulative myocytolysis throughout the entire focus. Wavy fiber and colliquative myocytolysis of non-specific ischemic lesions were seen only microscopically in both peripheral and subendocardial areas of infarcted foci. Coagulation necrosis was associated with obstructive thrombus formation in 79% of cases as a result of absolute ischemia in the transmural type. Coagulative myocytolysis was associated with obstruction by plaque hemorrhage in 27% of cases, and multivessel disease was frequently encountered in the subendocardial type due to insufficient blood supply. Based on histochemical and immunohistochemical examinations, the ischemic lesions were graded in descending order of coagulation necrosis, coagulative myocytolysis, wavy fiber, and colliquative myocytolysis. The close relation between coagulation necrosis and the transmural type as well as that of coagulative myocytolysis with the subendocardial type suggests two different pathogenetic mechanisms of transmural and subendocardial infarction.

Diethylene glycol (DEG)-associated myocardial changes: A pilot investigation of chronic intoxication in guinea-pigs

The myocardium of guinea pigs fed on sublethal doses of diethylene glycol (DEG) over a period of 2-11 days was examined for microscopical and ultrastructural changes. Coagulative myocytolysis and loss of myofibrils, not observed in the controls, was patchily distributed throughout the myocardium. The accompanying ultrastructural features included swelling, pleomorphism and hyperplasia of mitochondria with an associated distension of the interfibrillary spaces and a displacement, distortion and rupture of adjacent myofibrils.

Neurogenic heart disease: A unifying hypothesis

Electrocardiographic abnormalities have been known to occur in the context of neurologic disease for a long time. These changes fall into 2 categories: arrhythmias and repolarization abnormalities. However, until relatively recently these changes were believed to represent purely electrophysiologic alterations and not real heart disease. It is now clear that some patients with neurogenic electrocardiographic changes show cardiac enzyme release and myofibrillar degeneration at autopsy. There are 4 major methods for producing myofibrillar degeneration (i.e., contraction band necrosis or coagulative myocytolysis): catecholamine infusion, stress-steroid, nervous system stimulation and reperfusion. The common thread connecting these 4 methods is the opening of receptor-operated calcium channels, resulting in intense contraction of cardiac muscle. Thus, neurogenic influence over cardiac function may represent a continuum. In the mild reversible circumstance, only the electrocardiographic change will be seen, whereas in the severe, irreversible situation, myofibrillar degeneration will ensue with release of cardiac enzymes. Cardiac cell death may be caused by oxygen free radicals produced by metabolism of catecholamines or reperfusion or both, after variable periods of ischemia. This concept represents a unifying hypothesis, tying together the clinical, physiologic, biochemical and pathologic findings in neurogenic heart disease.

Protective effects of slow channel calcium antagonists on noradrenaline induced myocardial necrosis.

Catecholamine excess results in two distinct forms of coagulative myocytolysis, apparently due to increased membrane permeability followed by a large influx of calcium. To determine if three slow channel calcium antagonists, verapamil, nifedipine, and diltiazem, could reduce the calcium overload and prevent the development of noradrenaline induced acute myocardial contraction band lesions, 48 adult mongrel dogs in eight groups (n = 6) were continuously infused with saline alone, noradrenaline alone (4 micrograms X kg-1 X min-1), nifedipine (1 microgram X kg-1 X min-1), or other calcium blockers (10 micrograms X kg-1 X min-1) with saline or noradrenaline. After 15 minutes of pretreatment with a calcium antagonist, the antagonists were simultaneously infused with either saline or noradrenaline for 60 minutes. Nifedipine increased heart rate to the same degree as noradrenaline alone, whereas verapamil and diltiazem significantly suppressed the noradrenaline induced increases in heart rate. All three calcium antagonists reduced the increases in blood pressure and frequency of ventricular arrhythmias seen with noradrenaline alone. Only nifedipine produced a moderate increase in contractility (dP/dtmax) within 5 min and a pronounced synergistic increase when combined with noradrenaline. The effect of the other antagonists with noradrenaline was no different than the effect with noradrenaline alone. Contraction band lesions in the hearts of dogs in the saline and saline plus calcium antagonist groups were rare. The group receiving noradrenaline alone showed large numbers of the two predominant lesions: small paradiscal contraction band lesions and large holocytic contraction band lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental catecholamine-induced myocardial necrosis. II. Temporal development of isoproterenol-induced contraction band lesions correlated with ECG, hemodynamic and biochemical changes

Catecholamines have been shown to produce irreversible contraction band lesions of myocardial cells. However, little is known about the temporal appearance and correlation of the acute form of coagulative myocytolysis with ECG, hemodynamic and biochemical parameters. Groups of adult mongrel dogs were anesthetized with sodium pentobarbital, infused continuously with isoproterenol (2.5 micrograms/kg/min) and killed after periods of 0, 5, 15, 30, or 60 min. There were two predominant myocardial patterns: 'paradiscal' and 'holocytic' contraction band lesions. Either type of lesion was non-existent or rare in the control hearts. The small 'paradiscal' contraction band lesions were present as early as 5 min of isoproterenol infusion, particularly in the inner myocardial layer. The large 'holocytic' contraction band lesions were present by 15 min, however, they were not produced in any significant numbers before 30 min. Both types of contraction band lesions continued to accumulate up to 60 min. ST segment depression was the predominant ECG change. This occurred as early as 5 min when heart rate, blood pressure and dP/dt values had also significantly changed. The high-energy phosphates, phosphocreatine and ATP, started declining as early as 5 min. Furthermore, these phosphates and lactate were distributed in transmural gradients across the left ventricular wall with the greatest change in the endocardial third. This was also the site of the largest accumulation of each type of contraction band lesion. While the lesions correlated with certain biochemical and hemodynamic changes, the underlying pathophysiology is more complex than ischemia or high-energy phosphate depletion alone.

Reactive mobility of dendrites

Genetically hypertensive and normotensive rats were subjected to acute myocardial injury by a single subcutaneous injection of adrenaline (0.5 mg/100 g bw). The animals were sacrificed one day later. The lesions showed the signs of focal coagulative necrosis and intracellular myocytolysis. The damaged cardiomyocytes with high sarcolemmal permeability for blood plasma proteins were more widespread in the hypertensive versus normotensive rats. Intracellular myocytolysis, which is not associated with alterations in the cell membrane, was found in both experimental groups at an equal rate. The data agree with the concepts of alterations in biological membranes in genetically determined arterial hypertension.

Glutathione depletion increases chemiluminescence emission and lipid peroxidation in the heart

Diamide, CDNB and phorone were used to deplete glutathione in retrogradely perfused rat hearts. Following glutathione depletion the spontaneous chemiluminescence increased by 70%, irrespective of the agent used. The glutathione depletion and the chemiluminescence emission were associated to an increase of malondialdehyde content in the heart, as determined by HPLC. Under these conditions the heart function was impaired and histological examination showed a coagulative myocytolysis, a pattern already described in human and experimental pathology, where a key role is attributed to a Ca 2+ homeostasis impairment.