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Biomedical subjects

M C Fishbein

Publications and source records attributed to M C Fishbein.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of recombinant apolipoprotein A-I(Milano) on aortic atherosclerosis in apolipoprotein E-deficient mice.

BACKGROUND: We previously reported marked inhibitory effects of recombinant apolipoprotein (apo) A-I(Milano)/phospholipid complex (A-I[Milano]/PC) on neointimal lesions in balloon-injured iliofemoral arteries of hypercholesterolemic rabbits. In this study, we tested the hypothesis that apo A-I(Milano)/PC would inhibit aortic atherosclerosis in apo E-deficient mice. METHODS AND RESULTS: Thirty-five apo E-deficient mice fed a high-cholesterol diet were included in the study. Control mice were killed at 20 (n=8) or 25 (n=7) weeks. Treated mice received 18 injections of either 40 mg/kg apo A-I(Milano)/PC (n=15) or PC only (n=5) intravenously every other day from 20 weeks until death at 25 weeks. Aortic atherosclerosis was identified with Sudan IV staining. Lipid and macrophage contents of the aortic sinus plaques were measured after oil-red O and Mac-1 antibody staining, respectively, and quantified with computed morphometry. In control mice, from 20 to 25 weeks, aortic atherosclerosis increased by 59% (11 +/- 1% versus 17 +/- 5% of the aortic surface, P=.002), and lipid content increased by 45% (22 +/- 8% versus 32 +/- 6% of plaque area, P=.02) without a significant change in macrophage content (10.8 +/- 2% versus 13.2 +/- 6%). Compared with 20-week-old untreated control mice, PC only-treated mice at 25 weeks demonstrated a 32% increase in aortic atherosclerosis (11 +/- 1% versus 15 +/- 4%, P=.01) and an increase in lipid content (22 +/- 8% versus 47 +/- 3%, P<.0001) without a change in macrophage content (10.8 +/- 2% versus 11 +/- 2%). In comparison with 20-week-old untreated control mice, 25-week-old apo A-I(Milano)/PC-treated mice demonstrated no increase in aortic atherosclerosis (11 +/- 1% versus 10 +/- 4%, P=NS), a 40% reduction in lipid content (22 +/- 8% versus 13 +/- 8%, P=.01), and a 46% reduction in macrophage content (10.8 +/- 2% versus 5.8 +/- 2.9%; P=.03). Serum cholesterol levels were markedly elevated in all groups and did not change significantly with apo A-I(Milano)/PC or PC only. In vitro, apo A-I(Milano)/PC stimulated cholesterol efflux from cholesterol-loaded FU5AH hepatoma cell lines in a dose-dependent manner, whereas PC only or PC-free apo A-I(Miano) had no effect. CONCLUSIONS: Recombinant A-I(Milano)/PC prevented progression of aortic atherosclerosis and reduced lipid and macrophage content of plaques in apo E-deficient mice despite severe hypercholesterolemia. Thus, A-I(Milano)/PC may have a role in inhibiting progression and promoting stabilization of atherosclerosis.

Animals↗
PubMed1998

Enhancement of thrombolysis in vivo without skin and soft tissue damage by transcutaneous ultrasound.

Previous studies have shown that transcutaneous ultrasound enhances thrombolysis by streptokinase in animals in vivo; however, skin and soft tissue damage induced by ultrasound energy has been a major limitation. The objective of this study was to examine the efficacy of thrombolysis and damage to skin and soft tissues using a newly designed concentrated ultrasound system with a cooling manifold. Using a rabbit model with iliofemoral arterial thrombotic occlusions, 15 pairs of arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Streptokinase (25,000 unit/kg) was given intravenously. Skin temperature was maintained at 25-33 degrees C when ultrasound energy was applied. The serum level of creatine kinase, lactate dehydrogenase, red blood cell counts, and platelet counts were checked at baseline, after thrombus induction, and after ultrasound treatment. Fifteen of fifteen (100%) iliofemoral arteries were angiographically recanalized after ultrasound treatment. In contrast, only 1/15 (6.7%) contralateral arteries were patent after 1 hour. After the subsequent hour with heparin the patency was 14/15 in the ultrasound treated group and 3/15 in the control group. Histologically, the patent arteries had only minimal focal mural thrombus, whereas the angiographically occluded arteries had occlusive thrombi. There was no histologic evidence of ultrasound induced damage to overlying skin, soft tissues, or arteries. In addition, there was no significant rise of creatine kinase, lactate dehydrogenase, or decrease in red blood cell counts and platelet counts induced by ultrasound. In conclusion, transcutaneous concentrated ultrasound which significantly enhances streptokinase induced thrombolysis in vivo can be delivered without concomitant tissue damage. This simple combination therapy has clinical potential for safely treating patients with arterial or venous thromboses.

Angiography↗
PubMed1998

Noninvasive in vivo clot dissolution without a thrombolytic drug: recanalization of thrombosed iliofemoral arteries by transcutaneous ultrasound combined with intravenous infusion of microbubbles.

BACKGROUND: Previous in vivo studies have shown that microbubbles not only enhance the effectiveness of thrombolytic agents in the presence of ultrasound but may also augment clot dissolution without thrombolytic drugs. METHODS AND RESULTS: The objective of this study was to examine the efficacy of arterial clot disruption by a noninvasive, nonlytic approach with intravenous administration of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) and transcutaneous delivery of ultrasound alone. Pairs of iliofemoral arteries in 10 rabbits were randomized to receive transcutaneous ultrasound treatment or no ultrasound treatment after an acute artery thrombotic occlusion and intravenous PESDA infusion. Five arteries from 3 additional rabbits served as controls (ultrasound alone). All 10 iliofemoral arteries treated with PESDA + ultrasound were recanalized by angiography after ultrasound treatment. None of the 10 contralateral arteries treated with PESDA alone and none of the 5 arteries treated with ultrasound alone were patent after 1 hour. D-Dimer levels did not change after intravenous PESDA + ultrasound-mediated reperfusion. CONCLUSIONS: In vivo arterial clot dissolution can be achieved with intravenous microbubbles and transcutaneous ultrasound delivery alone. This technique has potential for clinical application in patients with acute arterial and venous thrombotic occlusions.

Animals↗
PubMed1998

Echocardiographic detection of Kaposi's sarcoma causing cardiac tamponade in a patient with acquired immunodeficiency syndrome.

Pericardial effusions are common in patients with acquired immunodeficiency syndrome (AIDS). The differential diagnosis is diverse, and in most cases the etiology cannot be established. A cardiac tamponade was diagnosed in a 32-year-old male with AIDS and systemic Kaposi's sarcoma. Transthoracic echocardiography revealed a large pericardial effusion with right atrial collapse and a mobile multilobular mass at the apex protruding into pericardial space. Autopsy showed that this mass was Kaposi's sarcoma confined to the epicardial fat. This is the first case of cardiac Kaposi's sarcoma detected premortem by echocardiography.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Perivascular delivery of a nitric oxide donor inhibits neointimal hyperplasia in vein grafts implanted in the arterial circulation.

OBJECTIVE: Nitric oxide has been reported to reduce intimal hyperplasia as a response to arterial injury. This study was designed to assess the possible effect of perivascular application of a nitric oxide donor on neointimal proliferation occurring in veins exposed to the dynamics of the arterial circulation in a hypercholesterolemic rabbit model. METHODS: Autologous jugular vein grafts were implanted in the carotid circulation of 20 hypercholesterolemic rabbits. A mixture of a biodegradable polymer and the nitric oxide donor, spermine/nitric oxide, which releases nitric oxide with a half-life of 39 minutes, was applied periadventitially at the time of implantation. Controls were veins bathed in saline solution, polymer alone, and polymer plus the carrier vehicle spermine without nitric oxide. Animals (n = 5 in each group) were put to death on day 28 for morphometric analysis, cell count, and immunohistochemical staining. RESULTS: Treatment with perivascular nitric oxide donor significantly decreased wall thickness (126 +/- 24 microm vs 208 +/- 45 microm, p = 0.0017) and area (124 +/- 22 microm2/microm vs 211 +/- 37 microm2/microm, p = 0.005). With the carrier vehicle spermine alone, there was a trend toward reduced intimal thickness, but the change was not statistically significant. In the grafts treated with nitric oxide donor, expression of insulin-like growth factor, fibroblast growth factor, thrombospondins, fibronectin, and tenascin was reduced. CONCLUSION: The periadventitial delivery of nitric oxide donor produces a reduction of neointimal hyperplasia in veins implanted in the arterial circulation. The mechanism of action is not entirely clear, but the reduction cannot be explained on the basis of decreased cell proliferation alone. Other possibilities are modulation of protein synthesis of vascular smooth muscle cells and production of extracellular matrix components.

Animals↗
PubMed1998

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry.

OBJECTIVES: We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND: The role of increased fibrosis in reentry formation during human VF is unclear. METHODS: Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS: Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS: In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.

Adolescent↗
PubMed1998

Clinical, echocardiographic, and pathologic features of aortic wall dehiscence of porcine bioprosthetic valves: a cause of rapidly progressive mitral regurgitation and heart failure after bioprosthetic mitral valve replacement.

The aim of this study was to define the clinical, echocardiographic, and pathologic correlates of commissural dehiscence of aortic wall from the stent post of the porcine bioprostheses in the mitral position. This form of valve degeneration was found in 5 of 23 explanted mitral bioprostheses. A thickened, separated aortic wall at multiple commissural sites along with other evidence of valve degeneration was identified in the three patients who had chronic congestive heart failure. A large dehiscence at a single commissural site with otherwise normal valve morphology was present in the two patients who had acute heart failure. Two dimensional/Doppler echocardiography showed a prolapsing or a flail anteriorly positioned leaflet and an eccentric posteriorly directed mitral regurgitation jet in all patients. These echocardiographic findings in patients with a porcine bioprosthetic mitral valve should suggest commissural dehiscence from the aortic wall as a possible mechanism of valve failure. Exclusive involvement of the porcine aortic bioprosthesis placed in the mitral position along with involvement of strut of the bioprosthesis facing the aortic root in all cases suggests excessive hemodynamic stress on the valve in the mitral position and in particular on the anteriorly placed strut as the potential cause of this form of valve degeneration.

Aged↗
PubMed1998

Forensic autopsy in a pathology training program.

OBJECTIVE: To review a satellite facility's autopsy experience with coroner's cases, to determine the volume and type of cases performed; and to evaluate the teaching value of forensic autopsies in a pathology residency training program. DESIGN: A retrospective review of 65 Los Angeles County Coroner cases performed at Cedars-Sinai Medical Center, Los Angeles, Calif, from 1992 to 1996 was undertaken. Data were retrieved from cause of death statements, medical report forms, and autopsy reports. RESULTS: In the 65 coroner's cases performed from 1992 to 1996, ages ranged from 6 months to 97 years. During this time period, the cases comprised 6.1% (65/1059) of all autopsies at Cedars-Sinai Medical Center and 11.3% (65/575) of autopsies excluding fetal and neonatal examinations. Manners of death in the cases were accidental (53.8%), natural (40.0%), suicide (4.6%), and undetermined (1.5%). The most common cause of death in natural deaths was related to heart disease (12/26 [46.2%]). Motor vehicle collisions were the most common cause of death (15/35 [42.9%]) in the accidental group. The remainder of the causes of death in both the natural and accidental groups encompassed a wide variety of pathologic processes and injuries. CONCLUSIONS: Forensic autopsies in a pathology residency training program have the potential to supplement a diminishing number of hospital autopsies. A wide variety of diseases are encountered through coroner's cases. Forensic autopsies contribute to residency training by providing experience in trauma cases and a variety of medical disorders.

Adolescent↗
PubMed1997

Induction of meandering functional reentrant wave front in isolated human atrial tissues.

BACKGROUND: The purpose of this study was to test the hypothesis that a single meandering functional reentrant wave front can result in rapid and irregular electrogram activity in human atrial tissues. METHODS AND RESULTS: The study used the explanted hearts of five human cardiac transplant recipients. Three right and two left atrial tissue samples, 3.4+/-0.3 mm thick, were excised and trimmed to 3.5x3.0 cm. The isolated atrium was placed endocardial surface down in a chamber with a 477 bipolar recording electrode array built into the bottom of the tissue bath. The interelectrode distance was 1.6 mm. The tissue was constantly superfused with 36.5 degrees C oxygenated Tyrode's solution at a rate of 10 mL/min. After eight baseline stimuli (S1) delivered at 400- or 600-ms cycle length from the edge of the tissue, a single premature stimulus (S2) was given at the center of the tissue to induce reentry. A total of nine episodes of reentry were induced with S1-S2 coupling intervals of 232+/-29 ms (range, 190 to 290 ms) and an S2 strength of 10+/-3 mA (range, 5 to 15 mA). In all samples, a single meandering reentrant wave front was induced, causing irregular and rapid bipolar electrogram activity. These wave fronts had a mean cycle length of 229+/-45 ms (160 to 290 ms) and persisted for 1.1+/-0.3 seconds (0.6 seconds to 2.5 seconds), or 5.2+/-1.4 (3 to 9) cycles, before spontaneous termination. CONCLUSIONS: A single meandering functional reentrant wave front can be induced in human atrial tissues and produce rapid and irregular electrical activity.

Adult↗
PubMed1997

Regional remodeling of atherosclerotic arteries: a major determinant of clinical manifestations of disease.

In this review we present the current data on remodeling, based on in vivo ultrasound imaging or postmortem histologic analysis of native peripheral and coronary arteries from animal models and studies in patients (coronary artery saphenous vein bypass grafts, lesions of restenosis after balloon angioplasty and other catheter-based interventions). Histologic and ultrasound imaging studies of arteries with atherosclerosis and after vascular injury reveal that arterial remodeling is common and that the cross-sectional area of the vessel is not constant. Compensatory enlargement, inadequate compensatory enlargement and shrinkage at the site of atherosclerotic lesions occurs in coronary and peripheral arteries. Current studies demonstrate that arterial remodeling is a major determinant of vessel lumen size.

Angioplasty, Balloon, Coronary↗
PubMed1997

Importance of location and timing of electrical stimuli in terminating sustained functional reentry in isolated swine ventricular tissues: evidence in support of a small reentrant circuit.

BACKGROUND: In excitable chemical media, a spiral wave is formed by reentrant excitation around a core and normal propagation away from the core. Whether or not this applies to cardiac muscle is unknown. METHODS AND RESULTS: In six isolated swine ventricular slices, we induced sustained episodes of functional reentry with a stationary core. A train of stimuli applied away from the core (7- to 8-mm distance) and near the core (within 1.6 mm) terminated 5 of 24 and 14 of 17 episodes of reentry, respectively (P<.001). When the stimulus was applied away from the core, successful terminations occurred when the line connecting the stimulus and the core was along the myocardial fiber orientation and when the coupling interval was 54+/-11% of the reentrant cycle length. Stimulation near the core terminated reentry primarily by propagation of the stimulus-induced wave fronts that closed up the excitable gap. However, in two episodes, the application of a stimulus near the core changed the electrogram morphology in only four bipolar pairs. This was sufficient to cause abrupt termination of reentry. CONCLUSIONS: (1) A thin layer of activation near the core is responsible for the maintenance of functional reentry. (2) Access to the tissue near the core is essential for the termination of functional reentry by a point stimulus. (3) To terminate reentry with a stimulus away from the core, the stimulus must occur at certain critical coupling intervals, and the line connecting the stimulus and the core must be roughly parallel to the fiber orientation.

Animals↗
PubMed1997

Highly localized arterial remodeling in patients with coronary atherosclerosis: an intravascular ultrasound study.

BACKGROUND: Preservation of luminal area and symmetry in the presence of irregular plaques necessitates local expansion of the artery wall. METHODS AND RESULTS: Cross-sectional dimensions of coronary arteries in 65 patients were measured with the use of intravascular ultrasound. A total of 104 arterial segments were studied, of which 88 had atherosclerosis; 16 served as nonatherosclerotic control segments. Three features of atherosclerotic arterial segments were classified: (1) plaque formation, (2) lumen shape, and (3) shape of arterial external elastic lamina. With our intravascular ultrasound-based three-level classification system, we identified three patterns that accounted for 89% of all atherosclerotic arterial segments: (1) concentric plaque with a circular lumen and a circular external elastic lamina (n= 17), (2) eccentric plaque with a circular lumen and an oval external elastic lamina (n=35), and (3) eccentric plaque with an oval lumen and a circular external elastic lamina (n=26). A circular lumen was preserved in 66% of all atherosclerotic arterial segments. Arterial segments with a circular lumen in the presence of an eccentric plaque had a significantly larger lumen area than the other two main groups (P<.05). CONCLUSIONS: With our intravascular ultrasound-based classification, we provided information regarding the local remodeling response in the coronary artery wall. In a majority of cases, a circular lumen is maintained. Failure of this highly localized response to be operative may contribute to the development of stenotic lesions at a specific site in the artery.

Aged↗
PubMed1997

Comparison of intravascular ultrasound measurements at the sites of balloon dilatations of femoral arteries with measurements of postmortem gross arterial segments at the same sites.

Intravascular ultrasound measurements of arterial cross-sectional area at the site of balloon dilatation are quantitatively accurate and consistent with measurements by digital planimetry. Lumen cross-sectional area determinations are virtually the same and the minor differences in total arterial cross-sectional area are probably related to the dehydration of each specimen, which occurred during the interval between studies. Thus, arterial disruption by balloon angioplasty does not interfere with the quantitative accuracy of intravascular ultrasound measurements.

Arteriosclerosis↗
PubMed1997

Documentation by intravascular ultrasound of thrombus overlying a small atheromatous plaque in a coronary artery in unstable angina pectoris and in acute myocardial infarction.

Rupture of atheromatous plaques leading to acute coronary syndromes usually occur in lipid-reach and well-developed coronary lesions. We describe 2 unusual patients with acute coronary syndromes in whom there was angiographic and intravascular ultrasound evidence of an intraluminal thrombus overlying a small, nonocclusive plaque in an enlarged coronary artery.

Adult↗
PubMed1997

Cellular graded responses and ventricular vulnerability to reentry by a premature stimulus in isolated canine ventricle.

BACKGROUND: The cellular mechanism by which a point strong premature stimulus (S2) induces reentry is unknown. We hypothesized that cellular graded responses induced by an S2 mediate and control tissue vulnerability to reentry. METHODS AND RESULTS: Reentry is induced in normal canine ventricular epicardial slices (30x38x2 mm, n=30) by an S2 at intervals shorter than the effective refractory period. The S1 is applied at the edge and the S2 at the center of the tissue. The line connecting the S1-S2 sites is parallel to the long axis of the fiber orientation. Isochronal activation maps were constructed with 56 to 480 bipolar electrodes, and the activation pattern was visualized dynamically. Reentry induced by an S2 is mediated by the graded responses as follows: The induced graded responses propagate with decrement toward recovered cells. When the amplitude of the propagated depolarizing graded responses reaches threshold relative to the recovering cells, an action potential is initiated along the fiber 2 to 3 mm away from the cathode of the S2. The distally initiated activation wave front blocks near the S2 site because the same S2-induced graded response prolongs the refractory period. The "broken" wave front then circulates around both sides of the block and reenters when the site of block recovers its excitability, completing the first figure-eight reentry cycle. Reentry cannot be induced when the S2 strength is >72+/-21 mA (upper limit of vulnerability) because these strong S2-induced graded responses convert the unidirectional block to bidirectional block by excess prolongation of the refractoriness. CONCLUSIONS: We conclude that the magnitude and the propagation of S2-induced cellular graded responses mediate and control vulnerability to reentry in the ventricular epicardium.

Action Potentials↗