Heart and vessels. Supplement最新文献

Two series of experiments were carried out using isolated, perfused rabbit hearts to elucidate the mechanisms of initiation and maintenance of ventricular fibrillation in the absence of ischemia. In the first series, either single premature or rapid electrical stimulation induced ventricular fibrillation, during which the spread of excitation was studied by recording electrograms from the endocardial and epicardial surfaces of both ventricles. Left ventricular endocardial stimulation appeared to induce fibrillation most easily. Initiation of ventricular fibrillation was preceded by the spread of areas showing a conduction delay. In certain instances, excitation of the endocardial and subendocardial tissue was necessary for the maintenance of repetitive responses. Injury to the endocardial and subendocardial layers of a ventricle (or both ventricles) by formaldehyde perfusion made the initiation of fibrillation more difficult, although complete prevention of fibrillation required extensive injury with a significant reduction in the excitable myocardial mass. In the second series of experiments, sustained ventricular fibrillation was produced by rapid electrical stimulation and the effects of several antiarrhythmic agents or electrolytes were studied by recording transmembrane action potentials of subepicardial ventricular muscle fibers with microelectrodes. Quinidine, lidocaine, and high K+ concentration significantly decreased the frequency of cellular depolarization and terminated fibrillation in all the 14 hearts studied. These agents suppressed local responses and small action potentials, and made the action potentials more uniform. In 5 of the 14 hearts in these three groups, termination of fibrillation was followed by either transient or prolonged periods of regular ventricular tachycardia. High Mg2+ concentration and bretylium tosylate tended to hyperpolarize the cell membrane, but less markedly decreased the frequency of cellular discharge. Defibrillation was achieved in only two of the ten hearts in which these two interventions were tested. Lanatoside C shortened the action potential duration, sometimes increased the frequency of cellular depolarization, and tended to sustain fibrillatory movements. These observations suggest the role of numerous microreentry movements in both the initiation and maintenance of ventricular fibrillation, although unifocal, ectopic impulse formation may not be definitely ruled out as an initiating mechanism. The possible defibrillating effect of certain antiarrhythmic agents is suggested.

The morphologic criteria in diagnosing myocarditis are detailed. In fulminant cases, apart from the inflammatory infiltrate which often consists of chronic inflammatory cells, necrosis is found, frequently in the form of myocytolysis. Two groups of patients are analyzed. The first consisted of 214 cases who were clinically suspected of suffering from myocarditis. In 50% of these cases, the clinical suspicion was confirmed by morphologic examination of tissue obtained by endomyocardial biopsy. The other group of patients were suspected of having dilated cardiomyopathy and consisted of 1200 patients; in 300 of these patients, myocarditis was diagnosed morphologically by biopsy. Following sequential biopsies monitoring the response to treatment with corticosteroids and immunosuppressive agents, a classification into active, ongoing, resolving (healing), or resolved (healed) forms has been advanced. The different stages depend on the severity of the inflammatory infiltrate, the site of the inflammatory cells, the presence or absence of necrosis of adjacent myocardial fibers, and the degree of fibrosis. It has been emphasized that clear concepts and a uniform approach are essential in diagnosing myocarditis, not only to achieve precise diagnosis, accurately monitoring the response to therapy, but also in helping to establish the pathogenetic pathways for certain forms of cardiomyopathy.

Light- and electron-microscopic studies and immunohistochemical procedures were carried out on blood eosinophils and left ventricular endomyocardial biopsies from a 68-year-old man with an eosinophilia of 8.2 X 10(9)/l and congestive cardiac failure due to eosinophilic endomyocardial disease. Some blood eosinophils were vacuolated and degranulated, and reversal of the normal staining pattern of eosinophil granules was seen by means of electron microscopy. The biopsies showed degenerative changes in the cardiac myocytes, with interstitial fibrosis and infiltration by numerous eosinophils, mast cells, and macrophages. Eosinophils infiltrating the myocardium showed a decrease in the number of granules, many of which were indistinct or contained dissolving crystalloids, which occasionally were seen to be discharged onto the surface of adjacent cardiac myocytes. Immunohistochemical studies of the endomyocardial biopsies with a monoclonal antibody, which is specific for activated eosinophils and binds to the secreted forms of eosinophil cationic protein (ECP) and eosinophil protein-X (EP-X), demonstrated that the lesions contained numerous activated eosinophils and secreted ECP and EP-X. These findings support the concept that in eosinophilic endomyocardial disease, activated eosinophils infiltrate and degranulate in the myocardium, releasing eosinophil cationic proteins which then damage adjacent myocardial cells.

Left ventricular biopsies from 376 patients (including 78 patients undergoing bypass surgery) were analyzed by light microscopy (necrosis, infiltration with or without fibrosis) and by immunohistology (bound antibodies). Circulating antisarcolemmal antibodies (ASA) were determined at the time of biopsy using a double-sandwich technique. Circulating antimyolemmal antibodies were assessed in intact rat and human cardiocytes. Histologic findings, heart catheterization, and echocardiography together with the patient's history established the diagnosis of perimyocarditis, myocarditis, postmyocarditic dilated cardiomyopathy, healed myocarditis, and healed perimyocarditis. Both bound and circulating ASA were found in up to 100% of cases in acute inflammatory heart disease and postmyocarditic cardiomyopathy, indicating a secondary immunopathogenesis of the myocardial disease. Analysis of immunoglobulin subclasses revealed: IgG-binding does not discriminate between acute/healing/healed carditis and postmyocarditic dilated heart disease (61.1%-91.7% positive); IgM binding is diagnostic for acute or healing perimyocarditis but has a relatively low incidence (33.3%); IgA binding occurs in acute or healing myocarditis (45.5%), perimyocarditis (33.3%), and in postmyocarditic heart disease (39.4%), but not in controls; complement fixation was never seen in controls, but was seen in acute myocarditis (45.4%), perimyocarditis (25%), and postmyocarditic heart disease (46%). Pretreatment of cryostat sections with collagenase to avoid "nonspecific" binding of antibodies to collagen considerably reduced the sensitivity but increased the specificity. Thus, endomyocardial biopsy proved a safe and valuable method for the further analysis of patients with carditis and myocardial disease of unknown origin.

A new hydroxybenzyl alcohol derivative TA-064 exerts a positive inotropic action in experimental preparations. To assess the acute effects in man, we made a cardiac catheterization study of the hemodynamic responses to TA-064 (20 mg and/or 40 mg given orally) in eleven patients with refractory heart failure due to cardiomyopathy (nine patients with dilated cardiomyopathy and one with amyloidosis). All patients were already receiving full digitalis and diuretics therapy. The following statistically significant (P less than 0.05-0.01) effects were noted: Upon administration of 20 mg of the drug, the cardiac index (CI) increased from a mean +/- 1 SD of 1.6 +/- 0.4 to 2.1 +/- 0.6 l/min/m2; pulmonary capillary wedge pressure (PCW) fell from 25 +/- 5 to 21 +/- 5 mm Hg; right atrial pressure (RA) fell from 12 +/- 3 to 10 +/- 4 mm Hg. In contrast, when 40 mg TA-064 were administered orally, the CI increased from 1.7 +/- 0.4 to 2.4 +/- 0.9 l/min/m2; PCW fell from 25 +/- 8 to 20 +/- 6 mm Hg; pulmonary arterial mean pressure fell from 35 +/- 11 to 29 +/- 9 mm Hg. Neither systemic arterial mean pressure nor heart rate increased. No toxicity was observed. The plasma concentration of TA-064 increased dose-dependently and reached a peak value 0.5-1.5 h after oral administration. Plasma catecholamine levels revealed no significant changes before and after use of the drug; therefore, the mechanism of action may not have been mediated by catecholamine.

We studied the chronic effects of chlorpromazine (CPZ) on the myocardium of rats using light and electron microscopy. Wistar strain rats were divided into two groups and given either normal saline or CPZ intraperitoneally at a dose of 5 mg/kg body weight/day for 30 consecutive days. Myocardial degeneration, atrophic muscle fiber, and myocardial fibrosis were observed by light microscopy in all CPZ-treated rats. Ultrastructural alterations of the myocardium were also found in all CPZ-treated rats. They consisted of contracted myofibers, mitochondriosis, degenerated mitochondria, dilated sarcoplasmic reticulum, and increased collagen fibers. However, no abnormal histologic or ultrastructural changes were observed in the normal saline-treated rats. We therefore conclude that a chronic administration of a sedative dose of CPZ causes myocardial damage in rats.

An experimental model embodies an evaluation procedure that helps the investigator to choose between possible alternatives. In this paper, consideration is given to a variety of aspects related to the host-parasite relationship in Trypanosoma cruzi infection and disease. Although several animal species have been used, there is still a lack of consistent experimental studies. A few examples of investigations mainly in dogs, monkeys, and rabbits are briefly described, showing the diversity of methodological approaches and, therefore, the difficulty experienced in comparing results and interpretations. Emphasis was given to the need for a suitable model presenting all possible stage of the infection as seen in man, as well as the functional and organic disorders commonly seen in this disease. The alterations of the autonomic nervous system involving the heart and other organs in Chagas' disease was stressed.

Kawasaki disease, a pathologic syndrome known to occur in children, was first described in 1967 as mucocutaneous lymph node syndrome by Kawasaki. The disease occurs chiefly in infants under 4 years of age, presenting with symptoms similar to scarlet fever or Stevens-Johnson syndrome. The changes are found at postmortem and consist of multiple aneurysms and thrombosis, which occur predominantly in the coronary arteries and are responsible for sudden death in most cases. Kawasaki disease is a systemic, acute inflammatory disease entity and in the early stages shows diffuse, necrotizing necrosis. Vasculitis affects primarily the arterioles, venules, and capillaries. Once aneurysmal dilatation has taken place, the wall of the coronary aneurysm becomes thin and the basic structures are destroyed by infiltration of inflammatory cells, which is followed by scar formation within 1 month from the onset of the disease. Coronary arterial lesions are nowadays responsible for the increase of myocardial infarction among the patients. Causes of sudden death include acute ischemia from obstruction or narrowing of the main coronary artery due to thrombosis, thickening of the vascular walls, myocarditis, rupture, and involvement of the conduction system by inflammatory infiltrates, resulting in complete atrioventricular block.

In acute myocardiopathy and pericardiopathy, Coxsackie virus B infections are increasingly recognized as a cause of primary myocardial disease and may cause chronic cardiovascular disease. With other viruses, such as cytomegaloviruses and rubella virus, transplacental infection during pregnancy may occur, and this can cause the congenital rubella syndrome, which involves heart abnormalities. Other viruses are now under study. Myocarditis was observed in a newborn infant infected with Coxsackie virus B3, which was isolated by tissue culture methods. Experimental infection of Coxsackie virus A and B was studied in suckling mice and the histopathologic changes in heart muscle were observed. Laboratory findings of viral infection are very useful for clinical diagnosis, however care needs to be taken with respect to the obtaining of specimens, diagnostic procedures, and the assessment of results.