In order to evaluate the chronic in vivo effects of excessive catecholamine levels, and the potential for spontaneous reversibility of these effects, we employed a chronic two-week infusion of epinephrine in rats. Epinephrine infusion resulted in myocyte hypertrophy, left ventricular fibrotic degenerative changes, diminished response to adrenergic stimuli, and enhanced left ventricular papillary contractile responses to calcium. Two weeks after cessation of the epinephrine infusion, left ventricular fibrotic degenerative changes were reduced, and responses to adrenergic stimuli were partially restored. However, myocyte hypertrophy and the enhanced responses to calcium persisted in these animals. This study indicates the potential for spontaneous reversal of some of epinephrine's toxic effects, and further implies that the loss in adrenergic sensitivity in epinephrine-treated animals may be a desensitization phenomenon, while the alterations in calcium response are less readily reversed.

Previous observations have indicated lamellated ultrastructural lesions in the myocardium of a patient treated with methylphenidate (Ritalin) hydrochloride (MPH). A causal relationship between MPH exposure and these membranous changes was tested in the myocardium of rats and mice. Following injection of varying doses of MPH for different periods, myocardial ultrastructure was examined and lesions were quantified by stereological techniques. Myocardial tissue also was stained using techniques selective for acid phosphatase and for sarcoplasmic reticulum to identify possible pathogenetic mechanisms. MPH induced membrane accumulations and lamellations which were not membrane-bound and did not react for acid phosphatase, but stained positively for sarcoplasmic reticulum. Both lesions were highly focal, surrounded by normal appearing myocardial tissue. Lamellations were evident at the earliest timepoints examined and appeared to occur without lysosomal involvement. Lesions were still apparent 12 weeks after terminating MPH. These data suggest that MPH may have persistent, cumulative effects on the myocardium.

Pulmonary vein development was studied using serial histologic sections of normal human embryos of Carnegie stages 11 to 15. Three-dimensional models were created in the program Swivel 3D on a Macintosh IIfx computer. The position of the mesocardium was found to be an important factor in the placement of the vein. Since the vein grows through a gap in the myoepicardium of the dorsal atrial wall created by the mesocardium, the vein can only grow where the mesocardium is positioned. Displacement of the initially median pulmonary vein ostium into the left atrium appeared to be caused by the formation of the left valve of the sinus venosus. This latter structure displaces the mesocardium to the left from stage 14 and later, carrying the vein to the left as well. The subsequent development of several pulmonary veins from the original single pulmonary vein occurred later, as the apex of the heart rotated to the left and brought the left atrium into a dorsal midline position. The study shows that correct placement of the pulmonary vein in the left atrium is the consequence of the successful execution of a sequence of developmental events in cardiogenesis.

In this study, we assessed reactive DNA synthesis in mouse cardiac myocytes after injury in vivo using the Bromodeoxyuridine (BrdU) immunohistochemical method and clarified binucleated metamorphosis of S-phase cardiac myocytes in the myocardial healing process. The animals were injured by isoproterenol i.p., and studied 0, 1, 2, 3, 5 and 10 days after injury. Each animal was killed 3 hr after labeling with BrdU i.p. The BrdU labeling index was calculated 0, 1, 2, 3, 5 and 10 days after injury. Moreover, we observed the morphological difference of S-phase cardiac myocytes between Group A and Group B (A and B group were killed 3 hr and 3 days, respectively, after BrdU i.p.). Most of BrdU positive cells were mesenchymal fibroblastic, and BrdU positive cardiac myocytes were a minor phenomenon during healing process. In cardiac myocytes, the BrdU labeling index is 0.49 +/- 0.02 and 0.05 +/- 0.01 at day 3 and 0 after injury, respectively (P < 0.05). All BrdU positive cardiac myocytes were located around myocardial necrosis. All BrdU positive myocytes in Group A were mononucleated, whereas some were binucleated in Group B. These results indicated that some of the cardiac myocytes could synthesize DNA reactively even after birth, and that in a healing process, myocytic DNA synthesis is probably followed by binucleated metamorphosis.

We have characterized the coronary vascular reserve, left ventricular function and inotropic response in dogs with chronic heart failure consequent to intracoronary embolization (EMB) with 50 microns spheres. We conducted studies 12-39 months after embolization and contrasted the findings with normal (CON) dogs. Acute embolization produced sustained LV volume enlargement and increased wall thickness, reduction of LV ejection fraction and elevated end-diastolic pressures; resting catecholamine levels were also increased. Responses to phenylephrine, nitroprusside, and dobutamine were identical in CON and EMB and coronary vasodilator reserve was reduced despite larger coronary vascular volume. Analysis by light microscopy showed a diffuse focal and interstitial fibrosis distributed uniformly from endocardium to epicardium associated with 14% loss of myocytes. This created a functional separation of myocardial muscle bundles and a disruption of the syncytial nature of the heart. Electron microscopy of the areas of fibrosis revealed myocytes in states ranging from normal appearing, to ghosts with evidence of cytolysis and loss of the sarcolemma. This model of chronic congestive heart failure with LV systolic dysfunction and elevated LV diastolic pressures shares a number of features with the syndrome in humans.

Increased heart weight is known to be associated with polyploidy of myocardial nuclei. However, the relation between polyploidy and myocardial hypertrophy at a cellular level, i.e. myocyte hypertrophy, has not yet been investigated. The present study was conducted to reveal this relation in different regions in the heart using two recently developed techniques, i.e. flow cytometry to measure polyploidy and microscopic morphometry to measure myocyte dimensions in fixed tissue sections. We investigated the effect of pressure overload induced hypertrophy in subendocardial and subepicardial regions of 43 human left ventricles and transmural samples from 47 human right ventricles. In all regions the degree of polyploidy correlated well with myocyte volume indexed for body surface area. At equal extent of myocyte hypertrophy, the degree of polyploidy was higher in left ventricular samples than in right ventricular samples. In conclusion, pressure overload induced myocyte hypertrophy is associated with polyploidy, which is more pronounced in the left ventricle than in the right ventricle.

Blood capillary abnormalities accompanied by intramural small arterial lesions were reported in patients with microvascular angina (MVA), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM). We compared the ultrastructural changes of blood capillaries in myocardial biopsy samples from MVA, HCM, and DCM patients using electron microscopy and ultrastructural morphometry. Ten cross-sectioned views were selected from each patient at random, and the degree of cytoplasmic swelling of the endothelial cells was measured (transverse area of endothelial cell cytoplasm (E)/transverse area of the blood capillary (C)). The thickness of the basal lamina was also assessed (transverse area of basal lamina (BL)/C). The average value of the E/C ratio was in the order of control group < HCM < MVA < DCM, with significant differences among the groups (p < 0.001). The average value of the BL/C ratio was in the order of control group < MVA < HCM < DCM, with significant differences (p < 0.001) among the groups except between the HCM and DCM groups. In conclusion, swelling of the endothelial cells as well as luminal stenosis of small arteries and arterioles may be related to disturbed microcirculation in these patients.

Dilated cardiomyopathy is characterized by an increase in myocardial mass. In order to study the functional significance of myocellular hypertrophy in dilated cardiomyopathy, 40 left ventricular endomyocardial biopsies were investigated, by comparing morphometrical data with functional indexes. The extent of myofibril volume fraction was directly associated with a better functional condition, as measured by ejection fraction (p < 0.01) and cardiac index (p < 0.05). Patients with oversize nuclei (nuclear area being > or = 70 microns 2) had a worse functional status (p < 0.05), as determined by ejection fraction and cardiac index. Finally, the extent of interstitial fibrosis was directly correlated to mean right atrial pressure (p < 0.01), right ventricular end-diastolic pressure (p < 0.02) and mean pulmonary artery pressure (p < 0.02). In conclusion, a worse functional status correlates with a reduced myofibril volume fraction and an oversize nuclear area, as in hypertrophic cells undergoing regressive changes.

This paper presents a sudden death case of 16-year-old girl. She is assumed to have died of ventricular arrhythmia clinically. On autopsy, the right cardiac ventricle was markedly dilated due to extensive infiltration of fibroadipose tissue and resultant depletion of the myocytes, but there was no full thickness disappearance of the contractile element in any part. Considerable parts of remaining myocytes showed degenerative changes similar to those of dilated cardiomyopathy. The left ventricle was moderately dilated. It showed similar significant degenerative changes to the right ventricle, but the degree was less extensive than the right. These findings do not fill the diagnostic requirements of neither Uhl's anomaly nor parchment heart, which reveal almost total depletion of the right ventricular myocytes. However, the findings were consistent with arrhythmogenic right ventricular dysplasia, in case the concept of the entity is extended, we concluded that it would be better to adopt a term--cardiomyopathy--to this case rather than dysplasia. Because, there were considerable histological evidence of myocardial degeneration suggesting primary myocardial disease rather than congenital defect in nature. We diagnosed, therefore, this case as right ventricular dilated cardiomyopathy, comprising a type of dilated cardiomyopathy whose myocardial lesions predominate in the right compared to the left ventricle.

Four cases of lipomatous hamartoma of the interatrial septum (LHIAS) were diagnosed at autopsy, three in elderly women, two of whom were morbidly obese. One patient had signs of congestive cardiac failure, without other significant cardiopulmonary disease, which was thought to be a result of the interatrial lipomatous hamartoma, while in the others, the LHIAS was considered an incidental finding. This condition, previously considered a hypertrophic phenomenon, is now best described as hamartomatous, and is being recognized more frequently both by clinicians and pathologists.

Thirteen histologically-proven cases of endocarditis confined to the right side of the heart were found in 9406 consecutive autopsies. Eleven cases involved the tricuspid valve and two the atrial endocardium. Nine cases were in males and 4 in females. Only one case showed underlying valvular/endocardial disease. Eight cases were infective, with Staphylococcus aureus being the predominant organism, and 5 non-infective. For the infective cases, intravenous drug abuse was the commonest predisposing factor, and malignancy the commonest association for the non-infective. The commonest overall complication was lung abscess due to septic emboli in the 3 drug addicts, a common association in other reported series. These latter cases are particularly important to recognize, being generally more responsive to treatment than left-sided infective endocarditis.

The prolonged regional contractile failure of reperfused myocardium has usually been characterized in terms of systolic function, while only few reports on its diastolic function are available. None of these studies considered changes in the isovolumic diastole and the subsequent filling phase separately. Therefore, in the present study, the velocities of wall excursion during systole (Vsys), isovolumic diastole (Viso) and filling phase (Vfill) were determined in 12 anesthetized dogs. Additionally, post-ejection thickening (Pejt), a marker of left ventricular asynchrony, was determined. Measurements were performed under control conditions, during a 15 minute left circumflex (LCX) coronary artery occlusion (CAO) and at 10 minutes, 4 and 8 hours reperfusion. Heart rate, left ventricular pressure, and Vsys, Viso, Vfill, and Pejt of the anterior myocardium remained unchanged throughout the experiments. During CAO, systolic wall-thickening of the posterior wall was reversed to systolic wall-thinning. Upon reperfusion, Vsys started to recover (2.5 +/- 3.2 mm/s at 10 minutes) and gradually improved over 8 hours of reperfusion (4.6 +/- 3.2 mm/s at 4 hours, 6.4 +/- 1.5 mm/s at 8 hours). Viso became positive during CAO (9.4 +/- 7.1 mm/s vs. -5.6 +/- 3.9 mm/s under control conditions) and was unchanged at 10 minutes reperfusion (7.9 +/- 5.2 mm/s). After 4 hours and 8 hours of reperfusion, Viso recovered to 1.2 +/- 9.2 mm/s and -0.3 +/- 10.7 mm/s, respectively. Vfill also became positive during CAO (1.5 +/- 6.2 mm/s vs. -18 +/- 8.7 mm/s under control conditions). There was a quick recovery of Vfill (-9.4 +/- 7.5 mm/s) with the onset of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of blood flow in tissues at risk for infarction is necessary for in vivo studies of the pathologic effects of vascular occlusion. Such blood flow measurements are traditionally carried out using radioactive microspheres. These are expensive and may pose a significant hazard to laboratory personnel. In addition, disposal of radioactive wastes, especially radioactive carcasses, is an increasingly expensive and inconvenient process. To avoid these problems, we have developed a modified procedure using fluorescent microspheres. To measure blood flow, spheres are injected intravenously and a blood sample is taken. Following cardiectomy, appropriate segments of left ventricular myocardium are digested with proteases to release the spheres, which are then purified through sucrose gradients. The spheres may be counted manually using an epifluorescence microscope, or by flow cytometry. Comparison of this method with the traditional radioactive microsphere procedure reveals similar results for the two methods. Fluorescent microspheres should provide a useful and accurate alternative method for measuring blood flow in studies of vascular disease.