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Prazosin, an antagonist of alpha 1-adrenergic receptors, has been found to suppress the clinical and histological expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Suppression was more significant in females than in males and was a dose-dependent phenomenon. Analysis of the effect of other adrenergic receptor antagonists supports the conclusion that the suppressive effect of prazosin is a consequence of blockade of the alpha 1-receptor since treatment with either the alpha 2-antagonist yohimbine or the beta-antagonist propranolol exacerbated the disease, whereas treatment with the long-acting mixed alpha 1/alpha 2-antagonist phenoxybenzamine had some suppressive activity. Treatment with prazosin was also able to suppress clinical and histological signs of EAE in animals sensitized by adoptive transfer with activated spleen or lymph node cells. Whether prazosin acts through altering vascular permeability or the immune response, or both, remains to be determined.

Diabetes mellitus is a significant condition, affecting major segments of all population groups studied. With the introduction of insulin and oral hypoglycemic therapy, together with better understanding of diet and weight control gained over the past half century, the primary causes of diabetic morbidity and mortality have shifted in varying proportions from metabolic derangements, infection, and renal insufficiency to different types of cardiovascular disease. Despite extensive clinical and laboratory research on the etiology, pathogenesis, and even the existence of cardiovascular disease associated with diabetes mellitus, however, considerable debate is still apparent in this field. Our purpose is to present an overview of the subject of diabetic heart disease, with a critical analysis of epidemiologic, clinical, and pathological data. Some of this material will be addressed from the perspective of research in this area over the past decade by one of us (SMF), particularly in experimental hypertensive and diabetic cardiomyopathy. However, overall, an attempt will be made to provide an objective and balanced analysis in order to answer the question: does diabetic heart disease exist?

The morphology, distribution, and configuration of coiled perimysial fibers of rat heart papillary muscle were studied. Methods included bright-field light microscopy of silver-stained sections, scanning and transmission electron microscopy, and differential interference contrast light microscopy of unfixed and unstained specimens. Coiled fibers, elliptical in cross section, are arranged in a branched network that diverges from the muscle-tendon junction and is continuous throughout the length of the muscle and into the ventricle wall. Most fibers range in diameter from less than 1 micron to 10 micron and are parallel with the long axis of the muscle, although branching is common and oblique orientations are seen. Several myocytes are associated with each coiled perimysial fiber. Constituent fibrils (diameter, 40-50 nm) occur in bundles twisted within the fiber. Small satellite elastic fibers are parallel to the collagen fiber axes. Stereo analysis of the coiled perimysial fibers reveals helical configurations, as opposed to planar waviness, that become less convoluted or even straighten as the resting muscle is stretched. Calculations based on cross-sectional areas of fibers, changes in fiber configurations, and tensile moduli reported for collagen fibers of other tissues show that the potential tensile strength of the network of coiled perimysial fibers is sufficient to contribute significantly to the mechanical properties of papillary muscle. Detailed evaluations of possible roles of the coiled perimysial collagen fiber system as a function of passive stretch and contraction in ventricular wall, as well as in papillary muscle, warrant further study.

In order to determine if cardiac tissue from AIDS patients or patients with seropositivity to HIV-1 might be infected by HIV-1, portions of myocardium obtained postmortem were evaluated for HIV-1 DNA sequences. Cellular DNA was extracted and digested with EcoR1 and Southern blots were performed. One of three AIDS hearts was positive for HIV-1 DNA sequences without amplification, whereas two additional hearts were positive for HIV-1 DNA after amplification. Accordingly, other tissue from the heart positive for HIV-1 without amplification was studied by electron microscopy to localize HIV virions. Unexpectedly, large numbers of proliferating multilamellated membrane bodies were identified in myocytes, predominantly associated with mitochondria. Identical membrane bodies were found in two additional AIDS hearts, and in one heart from a patient with seropositivity to the AIDS virus, but in none of three similarly fixed controls. Immunocytochemistry for HIV core (p24) and envelope (gp120) antigens did not localize gold-labeled antibodies to the membrane bodies. We believe this membranopathy may be an HIV-1- or AIDS-specific abnormality of unknown etiology that may be related to the ultimate development of cardiomyopathy. In addition, our studies provide further support that HIV-1 may be present in AIDS hearts, although as yet we cannot state with certainty where the HIV-1 is located in these tissues.

A morphologic study of the small (50 to 200 micron) intramyocardial coronary arteries was performed. The cases chosen for study were selected from a relatively young group of patients without clinical evidence of alcoholic cardiomyopathy or pathologic evidence of large coronary artery disease, in order to evaluate alterations in the small vessels which could possibly be attributed to the chronic alcoholic state. Five basic vascular abnormalities were described. The most common alteration found in all nine cases was vascular wall edema (48 per cent), followed by perivascular fibrosis (42 per cent), vascular sclerosis (36 per cent), subendothelial humps (13 per cent), and vascular wall inflammation (11 per cent). The significance and pathogenesis of these changes were discussed. Primary endothelial cell damage was proposed as a common pathogenic mechanism for all five types of vascular abnormality. It was suggested that following endothelial damage, fluid and macromolecules penetrate into the vessel wall or into the perivascular space where, by incompletely understood processes, they induce vascular wall myocytes to produce collagen, elastin, and basement membrane-like substances. Evidence supporting this mechanism was derived from the common observation of vascular wall edema, from the occasional presence of erythrocytes and leukocytes within the vessel wall, and from experimental data in the literature. Several possible etiologic agents were implicated in the pathogenesis of endothelial and vessel wall injury. These included alcohol itself, acetaldehyde, biogenic amines, and magnesium deficiency. It is probable, however, that there are multiple etiologic factors which affect the small cardiac vessels of the chronic alcoholic. Finally, the proposal was advanced that the nonspecific pathology of the myocardium in chronic alcoholism may be a result of ischemia secondary to disease of the small intramyocardial coronary ateries.

A 40-year-old homosexual man with the acquired immunodeficiency syndrome (AIDS) presented with dyspnea and renal insufficiency. A chest radiograph showed cardiomegaly and prominent pulmonary arteries, without alveolar infiltrates. Swan-Ganz catheterization revealed pulmonary hypertension and no evidence of left-to-right shunt. Liver function tests were normal. He was treated empirically for Pneumocystis carinii pneumonia, but he died 3 days after admission. At autopsy, membranoproliferative glomerulonephritis type III, P. carinii pneumonia, and plexogenic pulmonary arteriopathy were found. The kidney and lung were studied by electron microscopy and immunohistochemistry. Electron-dense immunoglobulin deposits were identified in glomerular capillaries and were confirmed by immunohistochemistry, but the pulmonary plexogenic lesions were negative. The combination of membranoproliferative glomerulonephritis and plexogenic pulmonary arteriopathy has not been described in AIDS to date.