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Biomedical subjects

M C Fishbein

Publications and source records attributed to M C Fishbein.

At least 127 records · Page 7Linked to original sources

Sudden death of a carrier of X-linked Emery-Dreifuss muscular dystrophy.

OBJECTIVE: To report a sudden death in a female carrier of Emery-Dreifuss muscular dystrophy and to describe the cardiac abnormalities associated with this disease. STUDY DESIGN: Case series. SETTING: University hospital. PATIENTS: A 45-year-old carrier who died suddenly and two affected men who also died of cardiac manifestations of Emery-Dreifuss muscular dystrophy. MEASUREMENTS: Post-mortem gross pathologic and histopathologic study of the heart. RESULTS: All three hearts showed a unique pattern of pathologic findings. Marked loss of atrial myocardium had occurred. Myocardium had been replaced by adipose and fibrous tissue. The conduction system showed no significant abnormalities. Varying degrees of interstitial and replacement fibrosis were present in the ventricular myocardium. CONCLUSIONS: Emery-Dreifuss muscular dystrophy is associated with characteristic pathologic changes in the heart that can cause death in female carriers and affected men. Female carriers should be identified and evaluated because of the risk for sudden cardiac death.

Adult↗

Use of laser energy to treat central pulmonary emboli: a preliminary report.

We evaluated the ability and safety of a laser fiber placed percutaneously into a pig's lobar pulmonary artery to lyse pulmonary artery blood clots that were created in situ. We developed a model to create blood clots in situ that could be placed in any desired location with a radio-opaque marker at the clot position. An excimer laser delivered energy to a flexible 600 microns fiber in three experiments and a coaxial 1.6 mm multifiber catheter in the last experiment. Pre- and postprocedure angiograms obtained from each experiment demonstrated that partial laser dissolution of central pulmonary emboli in four pigs was accomplished successfully. To avoid perforation, it is imperative that the laser fiber remain coaxial during the entire lasing process. These results suggest that laser dissolution may become an adjunctive procedure for the treatment of central pulmonary emboli in those patients who cannot be treated medically.

Animals↗

Histopathologic correlation of the three-layered intravascular ultrasound appearance of normal adult human muscular arteries.

The purpose of this study was to correlate intravascular ultrasound images from normal peripheral muscular arteries with the microscopic arterial components by using surgical microdissection techniques. There has been uncertainty about the precise anatomic constituents that are represented by the intravascular ultrasound three-layer image in human peripheral arteries. Forty of 66 grossly normal human femoropopliteal arterial segments obtained at autopsy were found to have a three-layered appearance and were subjected to selective surgical microdissection of intima, media, or adventitia. After microdissection, arteries were imaged with a 30 MHz intravascular ultrasound system; two observers blindly reviewed video tapes to assess for the presence or absence of a one-, two-, or three-layered arterial appearance. Removal of internal elastic lamina and/or intima results in a weak but evident inner ultrasound acoustic interface as a result of the media, which is normally echo-lucent. Removal of the adventitia and/or external elastic lamina results in a weak outer ultrasound acoustic interface. Isolated removal of the media does not alter the three-layered ultrasound image. In normal adult human femoropopliteal arteries the inner bright acoustic reflection (layer) is derived from the interface of blood with the intima and internal elastic lamina and the second bright interface (third layer) is from the external elastic lamina and adventitia. The mid-echo-lucent zone is the result of the media. However, any portion of the arterial wall, including muscular media, can act as an acoustic interface.

Adult↗

Implantation and recovery of temporary metallic stents in canine coronary arteries.

OBJECTIVES: The purpose of this study was to test the feasibility of implanting and retrieving a heat-activated recoverable temporary stent and to determine its effect on the angiographic, gross and histologic appearance of a normal coronary artery wall. BACKGROUND: Permanent coronary stenting is associated with a significant incidence of thrombosis, bleeding and vascular complications. These may be avoided by temporarily stenting for a period of hours to several days. METHODS: Seventy-eight stents constructed from the shape-memory nickel-titanium alloy nitinol were deployed by balloon expansion in the coronary arteries of 28 dogs and left in place for up to 6 months. Thirty minutes to 1 week after implantation, 70 stents were recovered by flushing the coronary arteries with 3 to 5 ml of 75 degrees C lactated Ringer solution, with collapse of the stent over a recovery catheter and subsequent withdrawal. RESULTS: All stents were successfully recovered and removed percutaneously. Mean vessel diameter after stenting was 12 +/- 6% (p < 0.05) greater than baseline diameter. Mean vessel diameter after stent removal remained enlarged (6 +/- 3%, p < 0.05). No angiographic or gross evidence of thrombosis, dissection, embolization, migration or spasm was associated with implantation or recovery. Microscopic examination revealed minor intimal injury in 40 segments (51%). Microscopic focal medial necrosis was associated with mural platelet-fibrin thrombus in 23 stented segments (29%) and media was interrupted in 7 (9%). CONCLUSIONS: This study demonstrates the feasibility of a new method of temporary stenting that uses the thermoelastic properties of nitinol to permit reliable recovery of the stent in normal canine coronary arteries.

Alloys↗

Effect of varying laser parameters on pulsed Ho:YAG ablation of bovine knee joint tissues.

We investigated the effect of varying laser parameters on ablation of fresh bovine knee joint tissues (fibrocartilage, hyaline cartilage, and bone) with a free-running Ho:YAG laser. Ablation rate was measured in saline for each tissue type as a function of laser fluence (160-950 J/cm2), pulse width (150-450 microseconds, full width at half maximum), and fiber core diameter (400 and 600 microns). A weight that was attached to the fiber end was used to exert a constant pressure of 40 g/mm2 to the tissue underneath to ensure a constant contact between the fiber tip and the tissue throughout the ablation process. All tissues could be efficiently ablated, and the ablation rate increased linearly with the fluence. Change in laser pulse width and fiber core diameter resulted in minor variations in the ablation rate for fibro- and hyaline cartilage. On the other hand, use of longer pulses and/or the larger fiber significantly accelerated bone ablation. Histology analysis revealed that zones of thermal damage in Ho:YAG irradiated bovine knee joint tissues differed by tissue types and ranged between 100 and 400 microns, but were independent of fluence, pulse width, and fiber size within the range tested.

Animals↗

Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.

MRL/lpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset. When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRL/lpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet. The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRL/lpr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRL/lpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet. These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia.

Animals↗

Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation.

BACKGROUND: Although rupture of an atherosclerotic plaque is considered to be the cause of most acute coronary syndromes, the mechanism of plaque rupture is controversial. METHODS AND RESULTS: To test the hypothesis that plaque rupture occurs at sites of high circumferential stress in the diseased vessel, the distribution of stress was analyzed in 24 coronary artery lesions. Histological specimens from 12 coronary artery lesions that caused lethal myocardial infarction were compared with those from 12 stable control lesions. A finite element model was used to calculate the stress distributions at a mean intraluminal pressure of 110 mm Hg. The maximum circumferential stress in plaques that ruptured was significantly higher than maximum stress in stable specimens (4,091 +/- 1,199 versus 1,444 +/- 485 mm Hg, p < 0.0001). Twelve of 12 ruptured lesions had a total of 31 regions of stress concentration of more than 2,250 mm Hg (mean, 2.6 +/- 1.4 high stress regions per lesion); only one of 12 control lesions had a single stress concentration region of more than 2,250 mm Hg. In seven of 12 lethal lesions (58%), rupture occurred in the region of maximum circumferential stress; in 10 of the 12 lethal lesions (83%), rupture occurred in a region where computed stress was more than 2,250 mm Hg. CONCLUSIONS: These data suggest that concentrations of circumferential tensile stress in the atherosclerotic plaque may play an important role in plaque rupture and myocardial infarction. However, plaque rupture may not always occur at the region of highest stress, suggesting that local variations in plaque material properties contribute to plaque rupture.

Aged↗

Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.

Lipofuscin pigment, a terminal oxidation product, accumulates within cells during the normal aging process and under certain pathological conditions. We have analyzed a genetic cross between two inbred mouse strains, BALB/cJ and a subline of C57BL/6J, which differ in lipofuscin deposition. A comparison of the segregation pattern of cardiac lipofuscin with the albino locus (c) on mouse chromosome 7 revealed complete concordance. Analysis of spontaneous mutants of the tyrosinase gene, encoded by the albino locus, confirmed that the tyrosinase gene itself controls lipofuscin formation. Genetic analysis of other strains indicated that one or more additional genes cab contribute to the inheritance of lipofuscin. We also present evidence for an association between cardiac lipofuscin deposition and aortic fatty streak development in the mouse.

Albinism↗

Effects of hypophysectomy on vascular insulin-like growth factor-I gene expression after balloon denudation in rats.

Insulin-like growth factor-I (IGF-I) is a widely distributed mediator of the growth promoting effects of growth hormone (GH). We sought to determine whether the relationship between GH and IGF-I extends to the vascular system, where IGF-I is proposed to participate in the process of neointimal proliferation after balloon denudation. We show that in hypophysectomized rats basal aortic IGF-I mRNA is one-tenth that of normal rats and is increased after balloon denudation. The induction peaks at 7 days after balloon denudation at about 10-fold control levels, similar to normal rats. Treatment with GH restores basal IGF-I mRNA content to approximately half that of normal rats, without further increase in the relative magnitude of induction after balloon denudation. This local induction of IGF-I gene expression in the vessel wall following injury might explain why neointimal proliferation is not inhibited more profoundly after hypophysectomy.

Animals↗

In vitro validation of three-dimensional intravascular ultrasound for the evaluation of arterial injury after balloon angioplasty.

OBJECTIVES: The hypothesis of this study was that three-dimensional ultrasound imaging would facilitate the evaluation of arterial dissection after balloon angioplasty. BACKGROUND: The presence and extent of arterial dissection occurring at the time of balloon angioplasty may be important predictors of abrupt vessel closure or late restenosis. METHODS: Forty-one human arterial segments obtained after death were imaged in an in vitro system at physiologic pressure (80 to 100 mm Hg) before and after balloon angioplasty. Images were acquired with a 20- to 30-MHz mechanical intravascular ultrasound imaging system (Cardiovascular Imaging Systems) with a constant pullback technique (1 mm/s). Standard 0.5-in. (1.27-cm) video tapes were used for data storage and later playback for analog to digital conversion. Digitized data were reconstructed to three-dimensional images with use of voxel space modeling. The vessels were opened longitudinally and subjected to pathologic examination, photographed and classified histologically as normal, fibrous or calcified. Dissection was defined as a disruption and separation of components of the arterial wall. The length and depth of arterial dissection were evaluated grossly and microscopically. RESULTS: Of the 41 arteries studied, 36 (88%) exhibited dissection on pathologic examination after balloon angioplasty. Three-dimensional reconstruction of intravascular ultrasound images identified dissection in 11 (92%) of 12 normal, 8 (100%) of 8 fibrous and 11 (69%) of 16 calcified arteries. Excellent agreement between ultrasound and pathologic findings was achieved in the evaluation of length and depth of dissection for histologically normal and fibrous arteries (kappa = 0.72 to 1.0). When the vessels were severely calcified, the agreement was not as good (kappa = 0.27 to 0.56), particularly in detection of small, non-raised intimal flaps. CONCLUSIONS: This histopathologic validation study suggests that three-dimensional intravascular ultrasound imaging facilitates the evaluation of both quantitative and morphologic features of arterial dissection induced by balloon angioplasty. The advantage of three-dimensional intravascular ultrasound is its ability to assess the length and morphology of arterial injury over an entire vessel segment.

Angioplasty, Balloon, Coronary↗

Proliferating cell nuclear antigen immunohistochemistry in rat aorta after balloon denudation. Comparison with thymidine and bromodeoxyuridine labeling.

The authors compared detection of proliferating vascular smooth muscle cells (SMC) in vitro and in vivo with proliferating cell nuclear antigen (PCNA) immunohistochemistry and two established methods: [3H]thymidine autoradiography and bromodeoxyuridine immunohistochemistry. Labeling with [3H]thymidine and bromodeoxyuridine of rat vascular SMC in culture stained 11% +/- 2% and 11% +/- 1% of cells, and PCNA immunohistochemistry 22% +/- 2% of cells. Proliferation in the media of the denuded rat aortae was highest 3 days after denudation: 4.2%, 3.8%, and 4.7% of labeled cells with [3H]thymidine, bromodeoxyuridine, and PCNA, respectively. In the intima, proliferation was highest 7 days after denudation with 42% [3H]thymidine, 40% bromodeoxyuridine, and 46% PCNA-positive cells. With double labeling, all [3H]thymidine-positive cells were PCNA positive, whereas some cells were only positive for PCNA. The authors conclude that PCNA immunohistochemistry compares favorably with [3H]thymidine autoradiography, and bromodeoxyuridine immunohistochemistry.

Animals↗

The severity of atherosclerosis at sites of plaque rupture with occlusive thrombosis in saphenous vein coronary artery bypass grafts.

Atherosclerotic plaque rupture with superimposed thrombosis is recognized as the lesion causing late, acute, thrombotic saphenous vein coronary artery bypass graft (CABG) occlusion. To determine the severity of atherosclerosis at the site of plaque rupture, 68 saphenous vein CABGs removed at the time of reoperation or at autopsy were studied. The study population consisted of 57 men, 64 +/- 9 years old, and nine women, 70 +/- 10 years old. The duration of graft implantation was 7.9 +/- 2.7 years (mean +/- S.D.). All CABGs were dissected from the hearts, fixed, decalcified, cut at 2 to 3 mm intervals, and processed routinely for histologic examination. A planimeter was used to measure total vessel, plaque, thrombus, and luminal cross-sectional areas at the site of plaque rupture with thrombosis in sections projected at 13.8 power magnification. At the site of atherosclerotic plaque rupture with superimposed thrombosis, the degree of stenosis due to plaque was: 90 +/- 11% for the right coronary artery grafts (n = 19); 94 +/- 7% for the left anterior descending artery grafts (n = 41), and 90 +/- 14% for the left circumflex artery (n = 8) grafts. Thus in saphenous vein CABGs, atherosclerotic plaque rupture with thrombosis usually occurs at sites of severe narrowing (mean = 93%) by preexisting atherosclerotic plaque.

Aged↗

Cardiac manifestations of acquired immune deficiency syndrome: a 1991 update.

Cardiac involvement is being identified more often clinically and at autopsy in patients with AIDS. Recent estimates suggest that in the United States as many as 5000 patients per year may have cardiac complications resulting from HIV infection. Patients with AIDS may have pericardial, myocardial, and/or endocardial disease. Pericardial tamponade and/or constriction may be related to neoplasms, infections, or nonspecific effusions. Myocardial dysfunction may result from specific neoplastic infiltration or myocarditis. Particularly intriguing is the role of HIV-1 in the nonspecific myocarditis and dilated cardiomyopathy that occurs in patients with AIDS. As in other debilitating conditions patients with AIDS can have nonbacterial thrombotic endocarditis. Infective endocarditis may be a complication, especially in AIDS associated with intravenous drug abuse. Most patients with AIDS have no overt clinical evidence of cardiac disease. When cardiac dysfunction does develop, the signs and symptoms are often misinterpreted to be the result of noncardiac causes (pulmonary failure or infection) which can mimic heart failure. This review is intended to alert the reader to the cardiac manifestations of AIDS, which present a number of diagnostic and therapeutic challenges.

Acquired Immunodeficiency Syndrome↗

The severity of coronary atherosclerosis at sites of plaque rupture with occlusive thrombosis.

Atherosclerotic plaque rupture with superimposed thrombosis is recognized as the lesion causing greater than 90% of acute myocardial infarctions. To determine the severity of atherosclerosis at the site of plaque rupture, 184 coronary arteries from autopsies of 162 patients who died of acute myocardial infarction were studied. There were 102 men, 72 +/- 10 years old (mean +/- SD), and 60 women, 75 +/- 8 years old. All arteries were dissected from the heart, fixed, decalcified, cut at 2 to 3 mm intervals and processed routinely for histologic examination. A planimeter was used to measure artery, plaque, thrombus and luminal cross-sectional area at the site of plaque rupture with thrombosis in sections projected at x13.8 magnification. At the site of atherosclerotic plaque rupture with superimposed thrombosis, the degree of stenosis due to plaque was: 90 +/- 7% for the right (n = 67), 91 +/- 6% for the left anterior descending (n = 79) and 91 +/- 6% for the left circumflex (n = 38) coronary arteries. Plaque rupture in fatal acute myocardial infarction occurs at sites of severe narrowing (mean 91%, range 67% to 99%). Thus, plaque rupture with thrombosis is unlikely to cause the fatal acute myocardial infarction in patients with mild to moderate coronary stenosis.

Adult↗

Positron emission tomography demonstrates that coronary sinus retroperfusion can restore regional myocardial perfusion and preserve metabolism.

Positron emission tomography was used to image blood flow and metabolic tracers in risk zone myocardium after left anterior descending coronary artery occlusion during synchronized coronary venous retroperfusion. Six control and seven intervention open chest dogs had occlusion of the mid left anterior descending coronary artery. Synchronized retroperfusion commenced 25 min later. Flow tracers (rubidium-82 and nitrogen-13 ammonia) were injected retrogradely. Three hours after coronary occlusion, fluorine-18 (F-18) deoxyglucose uptake in the control and treatment groups was compared. At 200 min of occlusion, infarct size was assessed. Retrograde flow tracer uptake was observed in the risk zone in the seven intervention dogs. Fluorine-18 deoxyglucose uptake in the risk zone was increased in five of the six intervention dogs but was reduced in five of the six control dogs. The risk zone to normal zone F-18 deoxyglucose count ratio was higher in the intervention than the control group (1.13 +/- 0.39 vs. 0.59 +/- 0.51; p less than 0.05). The endocardial subsegment risk zone to normal zone F-18 deoxyglucose count ratio was also significantly higher in the intervention group. Percent infarction in the risk zone was 70% lower in the group treated with synchronized retroperfusion than in the control group (18.4 +/- 22.6% vs. 61.2 +/- 25.4%; p less than 0.02). Thus, positron emission tomography revealed that retroperfusion could deliver oxygenated blood and maintain metabolism in risk zone myocardium. Infarct size was limited to 30% of that of control. In acute closure of the left anterior descending coronary artery, synchronized retroperfusion might be considered for maintaining viability of the jeopardized myocardium if the artery cannot be reopened rapidly.

Animals↗

Beneficial effects of coronary venous retroinfusion but not left atrial administration of superoxide dismutase on myocardial necrosis in pigs.

The efficacy of coronary venous versus left atrial administration of superoxide dismutase was studied in 24 open chest pigs which had 60 min of left anterior descending coronary artery occlusion followed by 3 h reperfusion. The pigs were randomly assigned to three treatment protocols: group A (n = 8) superoxide dismutase (5 mg kg-1) was infused into the great cardiac vein for 30 min beginning 15 min before reperfusion; group B (n = 8) superoxide dismutase (5 mg kg-1) was infused into the left atrium in a similar manner to group A; group C (n = 8) bovine serum albumin (5 mg kg-1) was infused into the great cardiac vein in the same manner as group A. Infarct size, expressed as percent of area at risk, was significantly smaller in group A (28.2 +/- 13.0%) than groups B (58.7 +/- 8.3%) and C (61.6 +/- 7.2%) (P less than 0.05). The results indicate that retroinfusion of superoxide dismutase into the great cardiac vein before reperfusion may be an effective treatment for the prevention of reperfusion injury, even in the absence of a well developed coronary collateral circulation. Antegrade (left atrial) administration of the same amount of superoxide dismutase did not decrease infarct size in pigs. The most likely explanation for this difference in efficacy is that drug delivery with left atrial administration is dependent on antegrade flow with reperfusion which is less reliable and less efficient than coronary venous retroinfusion. The latter provides a predictably high concentration of superoxide dismutase to the jeopardized myocardium during the period of ischaemia before reperfusion.

Animals↗

Differences in infarct size with lidocaine as compared with bretylium tosylate in acute myocardial ischemia and reperfusion in pigs.

The effects of the antiarrhythmic drugs lidocaine and bretylium tosylate on myocardial necrosis were studied in anesthetized pigs subjected to 60-min coronary occlusion followed by 3-h reperfusion. Group A (n = 7) received lidocaine (average dose +/- SD = 1,828 +/- 515 mg) before and during coronary occlusion and after reperfusion; the other series (group B, n = 7) received bretylium tosylate (3,457 +/- 1,323 mg). Infarct size was 16.3 +/- 14.7% in the lidocaine group as compared with 68.6 +/- 12.6% (p less than 0.01) in the bretylium group. In vitro release of superoxide anion from porcine granulocytes was studied using the lucigenin-dependent chemiluminescence technique. Lidocaine significantly reduced the peak chemiluminescence response to zymosan from 3.34 +/- 0.44 without lidocaine to 2.23 +/- 0.46 (p less than 0.01) and 1.06 +/- 0.17 mV (p less than 0.001), with lidocaine concentrations of 20 and 200 micrograms/ml, respectively. Bretylium had no effect on the chemiluminescence response. Adherence of porcine granulocytes to plastic was also reduced from 332 +/- 32 cells/mm2 (no lidocaine) to 247 +/- 35 and 206 +/- 26 cells/mm2 with lidocaine concentrations of 20 and 200 micrograms/ml, respectively (p less than 0.001). Bretylium had no significant effect. Eight additional bretylium-treated pigs received either rabbit antiporcine granulocyte serum (group C, n = 4) to reduce circulating granulocytes or nonimmune serum (group D, n = 4). Infract size in the granulocyte-depleted pigs was 26.6 +/- 5.6% as compared with 51.4 +/- 5.5% in pigs that received nonimmune serum (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗