Biomedical subjects

S M Factor

Publications and source records attributed to S M Factor.

At least 91 records · Page 5Linked to original sources

PubMed1989

Proliferative membranopathy and human immunodeficiency virus in AIDS hearts.

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.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Cardiac pathology in the hypertensive diabetic rat. Biventricular damage with right ventricular predominance.

The hypertensive-diabetic rat is a new small animal model of cardiomyopathy characterized by ventricular damage. To determine the extent of pathology in this model, quantitation of light microscopic changes in hearts from 15 hypertensive-diabetic rats and 15 age-matched controls was performed. The fraction of myocardium involved by interstitial fibrosis, myocyte necrosis, replacement fibrosis, vascular sclerosis and perivascular fibrosis was computed separately for right and left ventricles. Spontaneously dying as well as deliberately killed hypertensive-diabetic rats were studied. Spontaneously dying animals had higher systolic blood pressures compared with rats killed deliberately. Body weights were lower and lung weights higher in the former group. Left and right ventricular necrosis and fibrosis were increased in spontaneously dying compared with deliberately killed rats. The degree of right ventricular necrosis and fibrosis paralleled that in the left ventricle, but was, unexpectedly, several times greater in magnitude. Thus, quantitative histology in the hypertensive-diabetic rat reveals more cardiac necrosis and fibrosis, in either ventricle, from spontaneously dying animals compared with deliberately killed rats. This damage, coupled with major functional alterations in the viable myocardium, may lead to congestive heart failure or arrhythmia.

Animals↗

PubMed1988

The effects of acutely increased ventricular cavity pressure on intrinsic myocardial connective tissue.

Studies of normal hearts have revealed a variety of intrinsic connective tissue structures that surround and interconnect myocytes and ventricular mural layers. Among these structures, springlike coiled perimysial fibers, arrayed parallel to myocytes in the interstitial space, have been described in papillary muscle and ventricle. To evaluate the role of the coiled perimysial fibers under perturbed conditions, rat ventricles were filled with barium-gelatin under different pressures and fixed, and then the myocardium was impregnated with silver to visualize the connective tissue. Ventricles were filled at 30, 70 and 100 to 120 mm Hg. The coiled perimysial fibers were studied for their orientation, stretch, integrity and relation to sarcomere length. The coils were noted to embed within the fibrous anulus and to knot into an umbilical-like mass at the apex, thus anchoring them at both ends of the ventricle. They underwent focal straightening even at 30 mm Hg, with generalized straightening and disruption at the highest pressure; changes were most pronounced in the midventricle. Sarcomeres were maintained below 2.2 micron at 30 and 70 mm Hg of cavity pressure in regions of coiled perimysial fiber stretch; only with fiber disruption at 100 to 120 mm Hg were sarcomeres significantly lengthened. Other findings included connective tissue disruption between ventricular wall layers that allowed slippage of myocytes and mural thinning. These observations suggest that coiled perimysial fibers may act as a buffer to protect myocytes from damage under the effects of high cavity pressure.

Animals↗

PubMed1988

Prevention of hereditary cardiomyopathy in the Syrian hamster with chronic verapamil therapy.

The cardiomyopathic Syrian hamster develops genetically determined cardiac necrosis that invariably leads to premature death from congestive heart failure or arrhythmia. This hamster is a valuable model of human disease because it has many features in common with clinical dilated, congestive cardiomyopathy. Previous studies have shown that therapy for several weeks with the calcium channel blocking drug verapamil or the alpha-1 adrenoceptor blocking drug prazosin can prevent myocardial necrosis due to microvascular spasm. Other investigations have demonstrated the positive effects of verapamil in the early stages of disease. It is not clear, however, whether continued treatment can prevent the long-term expression of the cardiomyopathy or whether the disease is genetically predetermined. To address this question, hamsters were treated with oral verapamil for 7 to 8 months during the necrotizing, compensatory hypertrophy and early failure stages of disease. Analysis of myocardial pathologic and biochemical variables demonstrated that continuously treated animals were generally similar to unaffected control hamsters; discontinuous therapy led to partial protection. These findings demonstrate that virtually complete prevention of this hereditary disease is feasible; these results may have important implications for the treatment of human cardiomyopathy.

Adenosine Triphosphatases↗

PubMed1988

Increased intracranial pressure elicits hypertension, increased sympathetic activity, electrocardiographic abnormalities and myocardial damage in rats.

Intracranial pressure was increased in 59 rats by inflating a subdural balloon to a total mass volume of 0.3 ml. The increase in intracranial pressure ranged from 75 to greater than 500 mm Hg. With few exceptions, mean arterial pressure increased to as high as 227 mm Hg during the increase in intracranial pressure. Significant increases in plasma catecholamines, major electrocardiographic changes and a considerably shortened survival time were observed only in the rats that demonstrated an increase in mean arterial pressure greater than 50 mm Hg. A perfusion study with liquid silicone rubber (Microfil) revealed dilated irregular myocardial vessels with areas of focal constriction consistent with microvascular spasm. Histologic examination of the myocardium revealed widespread patches of contraction band necrosis and occasional contraction bands in the smooth muscle media of large coronary arteries. These observations suggest that myocardial damage after suddenly increased intracranial pressure resulted both from exposure to toxic levels of catecholamines and from myocardial reperfusion. Extension of these studies to humans suggests that a detailed assessment of myocardial function should be performed in victims of severe brain injury. Myocardial dysfunction may be a major determinant of the patient's prognosis or may render the heart unsuitable for transplantation.

Animals↗

PubMed1988

Myocardial adenylate cyclase activity in acute murine Chagas' disease.

We have studied the influence of myocardial infection with Trypanosoma cruzi on the beta-adrenergic adenylate cyclase complex in mouse myocardial membranes. The maximal rate of cAMP generation (Vmax) and the concentration of agonist associated with 50% of the maximal activity (apparent Kact) were determined for a series of agents. Six days after infection, the Vmax for isoproterenol significantly declines without a change in the apparent Kact. After 21 days of infection, both the Vmax and apparent Kact for isoproterenol are reduced. At 6 and 21 days of infection, the affinity of the beta-receptor for [125I]iodocyanopindolol declines from 0.84 to 3.6 and 3 nM, respectively, while the receptor density increases with the duration of infection from 33 to 57 and 82 fmol/mg protein, respectively. The Vmax (but not the apparent Kact) for forskolin and Mg2+- and Mn2+-associated activities declines also after 21 days. Another adenylate cyclase activity, which was stimulated by the nonhydrolyzable guanine nucleotide Gpp(NH)p, declines in relation to the duration of infection. Inhibitors of adenylate cyclase activity were also studied. Inhibition of adenylate cyclase activity by adenosine and by Gpp(NH)p (in the presence of forskolin) declines after 21 days of infection. The results suggested that the coupling proteins Ns and Ni, which mediate stimulatory or inhibitory control of receptors to adenylate cyclase activity, might be altered by infection. As monitored by cholera toxin- and pertussis toxin-dependent ADP ribosylation of their respective substrates, which include Ns and Ni proteins, respectively, there are declines in the availability of both substrates as a result of T. cruzi infection. For infected membranes, the addition of NADP enhances the magnitude of cholera toxin-dependent ADP ribosylation and renders the magnitude of pertussis toxin-dependent ADP ribosylation equal to that observed in uninfected membranes. The results support the hypothesis that infection with T. cruzi results in profound generalized alterations of the adenylate cyclase complex at several different sites.

Acute Disease↗

PubMed1988

Coiled perimysial fibers of papillary muscle in rat heart: morphology, distribution, and changes in configuration.

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.

Animals↗

PubMed1988

Comparative connective tissue structure-function relationships in biologic pumps.

A complex connective tissue framework exists in mammalian hearts that surrounds and interconnects individual myocytes and fascicles of cells. Recent evidence suggests that this connective tissue plays a role in maintaining shape, modulating contractile forces, and mediating elastic recoil during cavity filling and contraction. In order to analyze the involvement of connective tissue in pump contraction and recoil, we examined silver impregnated connective tissue in rat hearts which spontaneously jet through fluid ex vivo by contracting their cavities forcefully and then sucking fluid for the next cycle, and compared them to frog hearts which beat actively under the same conditions, but do not demonstrate jet propulsion. A further analysis was carried out in unrelated but analogous models: the squid and octopus. The former jets rapidly through the ocean, while the latter moves sinuously along the seabed. We observed highly interconnected myocytes in the rat heart, whereas frog myocytes are individually wrapped by connective tissue but are not interconnected. The squid mantle muscle is surrounded by a complex connective tissue grid that is tethered to each muscle cell, whereas the octopus mantle muscle cells are surrounded by connective tissue but are not tethered. These observations suggest that myocyte connective tissue tethering may be necessary for muscle cavities to generate forceful and coordinated contractions sufficient for rapid ejection and suction of fluid.

Animals↗

PubMed1988

The anatomy and pathophysiology of the microvasculature in different organs: relationship to vasculogenic necrosis and tissue damage.

This chapter presents the methodology as well as various applications of a silicone rubber (Microfil) prefusion technique for evaluation of the microcirculation. In the heart, Microfil perfusion has been used in conjunction with clearing techniques to elucidate normal anatomic relationships, to identify areas of myocardium at risk following vascular occlusion, and to observe dynamic events in the development of various cardiomyopathies. Advantages of the technique include in vivo applicability, ease of vascular filling, and ability to discriminate between adjacent vascular fields. Preliminary data from work in other organ systems including skeletal muscle, brain, liver, and lung are also presented.

Animals↗

PubMed1988

Catecholamine-associated smooth muscle contraction bands in the media of coronary arteries of brain-dead baboons.

In the brain death baboon model, the baboon experiences an autonomic storm with release of catecholamines both from the adrenal glands and from intracardiac sympathetic nerve endings. Since catecholamines may induce coronary arterial spasm, we looked for morphologic evidence of smooth muscle damage in the coronary arteries of 11 baboons that underwent induction of brain death under general anesthesia. Nine (82%) of the 11 animals showed coronary arterial smooth muscle contraction bands, and 9 (82%) of the 11 baboons also showed focal myocardial contraction bands and myocytolytic necrosis. Focal coronary arterial smooth muscle cell necrosis with intracytoplasmic calcium deposits were observed in three (33%) of the nine contraction band-positive cases. This study provides further support for the concept that medial smooth muscle contraction bands may be a morphologic marker of antemortem coronary arterial spasm.

Animals↗

PubMed1988

Structure and function of connective tissue in cardiac muscle: collagen types I and III in endomysial struts and pericellular fibers.

Heart myocytes and capillaries are enmeshed in a complex array of connective tissue structures arranged in several levels of organization: epimysium, the sheath of connective tissue that surrounds muscles; perimysium, which is associated with groups of cells; and endomysium, which surrounds and interconnects individual cells. The present paper is a review of work in this field with an emphasis on new, unpublished findings, including composition of endomysial fibers and disposition of newly described perimysial fibers. The role of scanning electron microscopy in the development of current understanding is also outlined. Biaxially arranged epimysial fibers form a sheath around papillary muscles and trabeculae that becomes increasingly well-oriented with the muscle axis during stretch. Perimysial structures are associated with groups of cells, and include weaves and septa of collagen, tendon-like fibers between weaves, ribbon-like fibers perpendicular to myocytes, and the newly described coiled perimysial fibers, which form an array in parallel with the myocytes and the epimysial net. The endomysium includes struts that bridge cells and pericellular fibers; both contain collagen types I and III. The evidence for the latter is presented in this paper and depends upon the use of antibody localization with fluorescent markers in light microscopy and colloidal gold for scanning electron microscopy. The implications of the composition of collagen fibers for myocardial function are discussed in relation to intra-cellular and other extra-cellular structures.

Animals↗

PubMed1987

Morphology, composition, and function of struts between cardiac myocytes of rat and hamster.

The morphology, composition, and function of struts that interconnect the lateral surfaces of cardiomyocytes were examined in the hearts of rats and hamsters. Methods included brightfield and fluorescent light microscopy, secondary and backscatter scanning electron microscopy, and transmission electron microscopy in conjunction with silver stain, cationic dye, and antibody to type-I collagen. These studies reveal a twisted, beaded appearance and a complex substructure of collagen fibrils embedded in a ground substance that has a positive reaction with cationic dye. A hierarchy of patterns of branching and attachment was seen among intercellular struts ranging in diameter from 0.1 micron to several micron. The hypothesis that struts tether not only the surfaces but the contractile lattices of laterally adjacent myocytes is supported by the following: (a) the attachments of struts to the collagen weave of the sarcolemma, often lateral to the level of Z bands, (b) the presence of collagen type I in a composite material arrangement, (c) the relative dispositions and configurational changes of struts and myocyte surfaces in various physiological states and induced, non-physiological perturbations of cardiac muscle, (d) the corrugated sarcolemmas with infoldings near Z bands, and (e) the continuity of intracellular filaments from Z bands to the inner aspect of the sarcolemma in relaxed and contracted myocytes. Implications of struts acting as tethers and sites for storage of energy in the motions of myocytes during the cardiac cycle are discussed.

Animals↗

PubMed1987

Membranoproliferative glomerulonephritis and plexogenic pulmonary arteriopathy in a homosexual man with acquired immunodeficiency syndrome.

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.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctional ("stunned") but viable myocardium.

Ultrastructural studies of the extracellular collagen matrix were made on the "stunned" myocardium using scanning, conventional and high voltage transmission electron microscopy and light microscopy. Regional myocardial dysfunction was produced by 12 sequential 5 minute occlusions of the left anterior descending coronary artery, separated by 10 minute intervals of reperfusion. A final 90 minute reperfusion period documented persistent myocardial dysfunction. At the end of the final reperfusion period, the percent systolic shortening, measured by sonomicrometers, was depressed significantly to 35 +/- 9% of baseline. The heart was then perfusion fixed, and samples were taken from both control and stunned areas. No changes associated with irreversible cellular damage were noted in the stunned region. However, scanning electron microscopy of the stunned area showed that the extracellular collagen matrix underwent profound structural changes. Collagen cables were roughened, uncoiled and discontinuous. Linear grooves on the surface of the myocytes were frequently seen, indicating complete loss of collagen cables. The usual dense collagen weave surrounding myocytes became patchy or absent. Myocyte to myocyte struts were sparse and frequently absent, with remnant nodular or nublike structures indicative of breakage. High voltage electron microscopy of the stunned area showed that the collagen struts were discontinuous and vacuolated with rounded tips. Light microscopy of silver-stained sections of the stunned tissue demonstrated large patchy areas that were devoid of silver, indicating absence of the collagen matrix. There was a progressive increase in percent systolic bulging during each sequential coronary occlusion, suggesting increasing myocardial compliance. These results indicate that the myocardial collagen matrix is severely damaged from reversible ischemic cell injury. The greater myocardial compliance and less effective contractile effort in the stunned myocardium might be explained on a structural basis: disruption of the mechanical coupling function provided by the extracellular collagen matrix.

Animals↗

PubMed1987

A nonflow basis for the vulnerability of the subendocardium.

The functional consequences of a transmural gradient of metabolism in the heart were studied in 19 dogs. The technique of retrograde blood flow diversion after coronary occlusion was used to deplete the ischemic myocardium of blood flow. Blood flow was uniformly and equally depleted in all layers, averaging 0.044 ml/min per g. With oxygen supply a controlled variable, transmural differences in metabolic demand can be addressed. In groups of dogs severe myocardial ischemia was induced for periods of 20 to 90 minutes. No necrosis was noted after 20 minutes of ischemia. Beginning at 30 minutes of blood flow depletion, necrosis progressed from the endocardium toward the epicardium in a "wave front" pattern. At 90 minutes of ischemia, approximately 70% of the area at risk was necrotic. Thus, the relative vulnerability of the endocardium as compared with the epicardium is due to nonflow factors, and probably dictated by transmural differences in metabolic activity. It would appear that myocardial metabolism as compared with blood flow occupies a primary and overriding role during the first 20 minutes of ischemia. Furthermore, differences in transmural metabolism also dictate subendocardial vulnerability for ischemic periods greater than 20 minutes, irrespective of blood flow. The role of blood flow in these events may be to modulate the rate of the transmural wave front of progressing necrosis after 20 minutes of ischemia.

Animals↗

PubMed1987

The use of glycerol-treated homologous pericardium as a substitute for cusps and chordae tendineae of the mitral valve in sheep.

In 11 weanling sheep chordae tendineae were replaced or a patch was implanted into the anterior mitral leaflet using homologous pericardium treated with 98% glycerol for 16.6 days on average. The sheep were electively sacrificed after 4, 6, 9, and 12 months. All animals showed competent mitral valves and good healing; only two sheep out of the patch-group showed small perforations at the suture line. Hemodynamic measurements and left ventricular angiography at rest and during stress test were normal except for the two cases. Histological examination revealed a distorsion and breakdown of pericardial collagen already after 4 months but the remnants of the graft were covered by a neointima of fibrous tissue. There were no signs of calcification and the new chordae tendineae and the patches were not shrunk, rigid or thickened. It is concluded that glycerol is a poor tanning agent, however, glycerol-treated pericardium seems to provide a lattice until fibrous tissue replacement has taken place. Therefore, we think it is a suitable material for mitral valve reconstruction.

Animals↗

PubMed1987

Microvascular reactivity of the myopathic Syrian hamster cremaster muscle.

The myopathic Syrian hamster is a genetic model of congestive heart failure that exhibits focal myocytolytic necrosis in both heart and skeletal muscle. Previous investigations of microvascular morphology in heart and skeletal muscle have shown severe arteriolar constrictions without fixed anatomical vessel lesions. This study tested the hypothesis that these constrictions indicate a hyperreactivity of the myopathic microvasculature in vivo and that the reactivity corresponds to the developmental course of myocyte pathology. The microcirculation of the cremaster muscle was studied in eight myopathic and six control hamsters in the active stage of necrosis (39-81 days of age) and five myopathic and six control hamsters in the later stage of muscle healing (150-213 days of age). The internal diameter of second order arterioles was measured during topically applied noradrenaline. The myopathic arterioles of the younger group constricted at significantly lower concentrations of noradrenaline (p less than 0.01) and constricted to 35-50% of their resting internal diameter over a narrower range of noradrenaline (p less than 0.01). This indicated both a reduced threshold to noradrenaline and an enhanced response to the agonist. Active myocytolytic necrosis was found in the contralateral cremaster muscle of each myopathic hamster. The older myopathic and control hamsters showed no significant differences in arteriolar responsiveness to applied noradrenaline and no active necrosis. These results indicate a relation between a hyperreactive microvasculature and active necrosis and a normal reacting microvasculature and diminished necrosis in the two phases of the disease. Thus a general correspondence between vascular responsiveness and myocyte pathology exists in this model of heart failure and muscular dystrophy.

Animals↗

PubMed1987

Alterations of the myocardial skeletal framework in acute myocardial infarction with and without ventricular rupture. A preliminary report.

Thinning and dilatation (expansion) of the infarct region and complete rupture of the ventricular wall are significant complications of acute transmural myocardial infarction associated with increased morbidity and mortality. The pathogenesis of these related events is unknown. Recent studies of myocardial connective tissue have delineated an extensive array of intercellular and pericellular structures which serve as a skeletal framework and which may modulate contractile activity. We have employed a modified silver impregnation method to visualize the connective tissue components by light microscopy. To explore whether the skeletal framework is altered in acute myocardial infarction with and without ventricular rupture, we studied 9 human hearts at autopsy, and 4 canine infarcts of known duration. The human infarctions included 4 nonruptured cases with infarcts 1-5 days old, and 5 ruptured cases with infarcts 3-10 days old. Sections from normal, lateral, and central infarct or ventricular rupture sites were stained with silver. The normal tissue from each heart served as a control. Silver staining was moderately decreased in the lateral infarct zones, and markedly decreased in the central non-ruptured infarct zones. In the 5 ventricular rupture cases, the rupture site had no silver staining. A similar pattern was observed in the 4 canine infarcts. Thus, we conclude that the skeletal framework is markedly altered in the central zone of acute myocardial infarction. The acute changes of silver stained connective tissue may contribute significantly to the development of infarct expansion or ventricular wall rupture.

Animals↗