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Biomedical subjects

M C Fishbein

Publications and source records attributed to M C Fishbein.

At least 163 records · Page 9Linked to original sources
PubMed1990

DNA flow cytometry of myocardial cell nuclei in paraffin-embedded, human autopsy, cardiac tissue.

Changes in nuclear DNA occur in myocytes as they grow and hypertrophy. We used DNA flow cytometry to study myocardial nuclei from paraffin-embedded human autopsy tissue. Forty hearts ranging from 310-1040 g were studied. Histograms generated for each heart showed peaks at the 2N and 4N positions. Two of 9 hearts weighing 310-430 g had 8N peaks as well. Fourteen of 17 hearts weighing 450-690 g also had 8N peaks but no 16N peaks. Twelve of 14 hearts weighing 710 to 1040 g had 8N peaks and 4 had 16N peaks as well. Contingency analysis showed statistically significant differences in the ploidy of nuclei from the three different groups of hearts. This study corroborates previous work indicating that DNA ploidy in myocardium increases with hypertrophy. Thus, flow cytometry of paraffin-embedded myocardium should be a useful technique to study DNA from archival material, obviating the need for fresh or frozen tissue.

Cardiomegaly↗
PubMed1989

Selective decrease in lysis of old thrombi after rapid administration of tissue-type plasminogen activator.

The safety of thrombolytic therapy of acute myocardial infarction could be improved if a method were developed to dissolve fresh occlusive coronary thrombus without simultaneously dissolving hemostatic thrombi outside the coronary arteries. This study is based on the assumption that, in a patient with evolving acute myocardial infarction, hemostatic thrombi are likely to be older than the thrombus responsible for occlusion of the coronary artery. It explored whether the relative rates of lysis of fresh and old thrombi could be influenced by the rapidity of recombinant tissue-type plasminogen activator (rt-PA) administration. In each of 17 dogs, two 1 h and two 24 h old thrombi were produced by inserting copper coils into both jugular and both femoral veins. After 24 h and 1 h, respectively, the coils with the thrombi were removed, weighed and inserted into the adjacent carotid and femoral arteries. A 1 mg/kg body weight dose of rt-PA was given either over 180 or over 30 min. The coils were removed and weights of the residual thrombi determined at the end of the 180 min infusion (Group I), at the end of the 30 min infusion (Group IIA) and 45 min after the 30 min infusion (Group IIB). The 24 h old thrombi were lysed significantly less than the 1 h old thrombi in all three experimental groups: 53.9 +/- 4.8% (mean +/- SE) versus 86.1 +/- 2.5% in Group I (p less than 0.001), 16.6 +/- 3.5% versus 65.2 +/- 6.0% in Group IIA (p less than 0.001) and 21.6 +/- 5.4% versus 91.7 +/- 1.7% in Group IIB (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Beneficial effects of coronary venous retroinfusion of superoxide dismutase and catalase on reperfusion arrhythmias, myocardial function, and infarct size in dogs.

The efficacy of coronary venous retroinfusion of superoxide dismutase and catalase was studied in anesthetized closed chest dogs with 90-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion. In group A, superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) were administered by a 30-min continuous right atrial infusion beginning 15 min before reperfusion and supplemented by a bolus injection of superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) through the great cardiac vein immediately before reperfusion. The treatment in group B was similar to that in group A, except that the bolus injection was into the right atrium. In the control group (group C), saline was administered in the same manner as in group A. Infarct size, expressed as a percentage of the risk area, was significantly smaller in group A (11.3 +/- 8.9%) than in groups B (31.3 +/- 21.1%) and C (43.0 +/- 16.9%; p less than 0.05). Regional function of the ischemic zone measured by two-dimensional echocardiography exhibited significantly (p less than 0.05) greater recovery after 3-h reperfusion in group A (30.3 +/- 8.4%) versus groups B (12.5 +/- 13.7%) and C (12.1 +/- 11.7%). Moreover, there were significantly fewer postreperfusion ventricular arrhythmias in group A as compared with groups B and C. The results of this study indicate that coronary venous retroinfusion is an effective method for delivery of superoxide dismutase and catalase.

Animals↗
PubMed1989

Sequential noninvasive assessment of left ventricular size, regional wall thickness and function during 3 hours of coronary artery occlusion and reperfusion: differential effects of reflow in dogs with small vs large areas at risk.

1. The present study was undertaken to determine noninvasively the sequential changes in left ventricular (LV) size, wall thickness and regional contractile function occurring during 3 h of proximal left anterior descending coronary artery occlusion (CAO), and their modification by reperfusion (REP) over a 7-day period. 2. Twenty, closed-chest, anesthetized dogs underwent CAO for 3 h and were reperfused for 7 days. Hemodynamics (aortic, LV pressure, LV dP/dt) and regional LV function were measured sequentially during CAO and reperfusion. The animals were killed at 7 days and infarct size was measured using the triphenyl-tetrazolium-chloride technique. Regional function (systolic fractional area change, FAC) was measured in 40 LV segments of 5 two-dimensional echo short-axis planes (8 segments per section). 3. At three hours of CAO, 14 dogs developed extensive areas of akinesis or dyskinesis in more than 6 segments (Group I, large risk area), whereas 6 dogs developed akinesis or dyskinesis in 6 segments or less (Group II, small risk area). Four dogs died between 12 and 48 h after REP in Group I and none of Group II died. Recovery of regional function after REP was significantly different between Groups I and II: in hypokinetic segments, FAC improved from 16.7 +/- 0.9% (mean +/- SEM) at 3 h of CAO to 25.4 +/- 3.2% at 24 h and to 34.9 +/- 2.0% at 7 days (66.3 +/- 3.4% of baseline) after REP in Group I; in Group II, FAC increased from 16.6 +/- 1.5% at 3 h of CAO to 48.5 +/- 7.4% at 24 h and to 52.4 +/- 1.6% (92.7 +/- 2.8% of baseline) at 7 days after REP. In akinetic/dyskinetic segments, FAC increased from -9.2 +/- 2.4% at 3 h of CAO to 8.2 +/- 2.6% at 72 h and to 8.3 +/- 3.2% (15.1 +/- 5.8% of baseline) at 7 days of REP in Group I; in Group II, FAC rose significantly from -7.6 +/- 1.6% at 3 h of CAO to 39.9 +/- 7.3% at 24 h and to 50.8 +/- 4.3% (89.2 +/- 4.9% of baseline) at 7 days after REP. There was a significant inverse correlation between the magnitude of compensatory hyperkinesis in the nonischemic wall and the extent of hypokinesis at 60 min (r = -0.82, P less than 0.001), but this correlation was less significant at 24 h (r = -0.64, P less than 0.01), 72 h (r = -0.53, P less than 0.02), and 7 days (r = -0.50, P less than 0.05) after REP.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1989

Identification of growth hormone at the myocardial cell surface.

Growth hormone immunoreactivity has been demonstrated in a variety of normal human tissues, and ectopic production has been documented in a number of malignant tumors. However, myocardium has not previously been reported to contain growth hormone. Monkey anti-rat growth hormone antiserum was used in a sensitive immunoperoxidase staining method to histologically localize growth hormone in myocardium obtained from normal rats and rats harboring growth hormone-secreting tumors. Immunoreactive growth hormone was localized to the myocardial cell surface and was not seen in vascular endothelial cells of small arteries, veins, or capillaries. No intracellular staining of myocytes was evident. Specific staining was abolished by neutralization with purified growth hormone. Specific staining was abolished by neutralization with purified growth hormone. Myocardial cells did not stain with anti-triiodothyronine or anti-thyroxine immune serum. The cell surface staining is consistent with the binding of growth hormone to the myocardial cell surface, as it is unlikely that the myocardium synthesizes growth hormone polypeptide. These findings suggest that growth hormone may have a direct growth promoting or metabolic effect on cardiac tissue.

Animals↗
PubMed1988

Long-term propranolol administration alters myocyte and ventricular geometry in rat hearts with and without infarction.

To determine the effects of long-term beta-adrenergic receptor blockade on adult rats with myocardial infarction, we studied 24 female Sprague-Dawley rats with myocardial infarction induced at 20-22 weeks of age. Two days after surgery, the animals were randomized to receive either propranolol (750 mg/l) in their drinking water or water alone for 5 weeks. Plastic, embedded, longitudinal and cross sections of septum (1 micron thick) were prepared for morphometric measurements. In untreated rats, infarction was followed by myocardial hypertrophy, as shown by significant increases in septal area (23%), myocyte length (19%), cross-sectional area (20%), and volume (43%) (p less than or equal to 0.05). In rats with and without infarction, beta-blockade resulted in decreased myocyte dimensions and increased left ventricular cavity dimensions. Propranolol had special effects in rats with infarction, resulting in significant blunting of increased cross-sectional area (15% less, p = 0.04) and a greater increase in left ventricular cavity dimensions (38% more, p = 0.04). Thus, propranolol blunts myocardial hypertrophy and increases left ventricular cavity dimensions in rats with myocardial infarction.

Analysis of Variance↗
PubMed1988

Ultrasonic plaque ablation. A new method for recanalization of partially or totally occluded arteries.

The potential application of ultrasonic energy for ablation of atherosclerotic plaques was studied in human atherosclerotic arteries with continuous and pulsed delivery of energy. With a prototype ultrasonic wire probe (n = 79 segments), there was gross reduction in vascular lesions as well as microscopic disruption of fibrous and calcified plaques. Normal portions of vessels appeared unaffected by the application of ultrasound. The prototype ultrasonic wire catheter ablated calcific deposits in less than 10 seconds. With this probe, all 26 complete atherosclerotic occlusions 0.5-5 cm in length were recanalized irrespective of the presence of calcium. Twenty-four of the segments were reopened in less than 20 seconds. By light microscopy, the site of plaque ablation was smooth, concave, and conformed to the shape of the probe tip. In 17 samples, there was evidence of thermal injury, and in six of the 79 samples studied with the prototype probe, there was vascular perforation. No vascular perforation occurred without thermal damage, when pulsed (rather than continuous) ultrasonic energy was used (n = 40) or when the duration of application was less than 30 seconds, with power output less than 25 W and with the probe oriented parallel to the wall (n = 26). Thus, by modifying the duration, mode, and magnitude of the ultrasonic power output, thermal injury and vascular perforation may be avoided. In vivo intra-arterial ultrasonic angioplasty of a canine chronic femoral fibrocellular occlusion was also performed. A preliminary in vivo study demonstrated feasibility of the percutaneous application of intra-arterial ultrasonic recanalization. Thus, ultrasonic energy appears to have potential as a method for ablation of occlusive atherosclerotic plaque.

Angiography↗
PubMed1988

Papillary muscle structure-function relations in the aging spontaneously hypertensive rat.

Isolated left ventricle papillary muscle mechanics and structure were studied in male spontaneously hypertensive (SHR) rats and two control groups of animals, the normotensive Wistar (NR) and the Wistar-Kyoto rat (WKY). Active tension and its first derivative (dT/dtmax) normalized for muscle cross-sectional area were increased in preparations from the SHR at all ages studied relative to control groups (P less than 0.01). However, when these parameters were normalized for myofibrillar cross-sectional area determined from electronmicroscopic point counting data, differences between groups were no longer significant. Force-velocity relations provided no evidence for a depression of shortening velocity at any load in the SHR at any age relative to the two control groups. The duration of mechanical activity, as determined by time-to-peak isometric tension and analysis of muscle force-velocity-time relations, was prolonged only in the 18 month old SHR (P less than 0.01). Thus, while changes in isolated muscle performance occur at a time when hemodynamic impairment is reported in the intact animal (male 18 month SHR), no evidence for depression of isolated muscle function is seen in the SHR at 6, 12 or 18 months of age.

Age Factors↗
PubMed1988

Cardiac architectural changes with hypertrophy induced by excess growth hormone in rats.

We have shown that excess growth hormone (GH) causes left ventricular hypertrophy in rats. To further characterize cell growth of this model, combined light and electron microscopic morphometric studies were done on 5- and 1-micron sections of the perfusion fixed left ventricle (LV) in 6 control (C) and 5 GH-stimulated rats. Total ventricular weight, LV weight and right ventricle weight were increased 45, 46, and 43%, respectively, in the rats after a few weeks of GH stimulation. However, neither the ratio of LV to body weight, nor right ventricle to body weight were significantly different between the two groups. Nuclei (n)/volume decreased by 25% in GH due to a decreased number of n/area (819 +/- 80 versus 718 +/- 52/mm2, p less than 0.05) and an increased n length (16.9 +/- 1.7 versus 19.7 +/- 0.5 micron, p less than 0.01). As the volume fraction of myocytes was the same in GH and C, the volume of myocytes/n increased (16.5 +/- 1.9 in C to 20.8 +/- 1.1 x 10(3) micron3 in GH, p less than 0.01). Since no change was found in cross-sectional area of myocytes (242 +/- 26 in C versus 244 +/- 23 micron2 in GH, p greater than 0.50) cell length/nucleus increased by 26% (68.5 +/- 8.6 in C versus 86.0 +/- 7.8 micron in GH, p less than 0.01). The average area of mid-LV wall increased by 35% in GH compared with C (p less than 0.01), but wall thickness was unchanged (2.1 +/- 0.4 in C versus 2.2 +/- 0.2 mm in GH, p greater than 0.20) as LV cavity radius increased (1.85 +/- 0.5 in C to 2.50 +/- 0.6 mm in GH, p = 0.06). With decreased developed pressure of LV in GH, systolic circumferential wall stress was unchanged (55.3 +/- 21.1 in C versus 57.2 +/- 22.5 x 10(3) dyne/cm2 in GH, p greater than 0.50). We conclude that left ventricular hypertrophy of this model is associated with cavity dilation and increased myocyte cell length; this adaptive response tends to minimize the effects of increased volume load on wall stress.

Adaptation, Physiological↗
PubMed1988

Differential prostacyclin production by human umbilical vasculature.

Using the avidin-biotin immunohistochemical technique with rabbit antihuman 6-keto-prostaglandin (PG)-F1 alpha (6KPGF), we studied the distribution of the stable prostacyclin metabolite, 6KPGF, in 14 formaldehyde-fixed human umbilical cords. All umbilical veins demonstrated intense endothelial cell staining. None of the arteries stained. To corroborate the immunohistochemical findings, three fresh umbilical cords were dissected to separate arteries from veins and then were incubated in oxygenated tissue baths containing Ringer's lactate (37 degrees C) for 30 minutes. Cumulative 6KPGF production as measured by radioimmunoassay of tissue effluents was markedly different between arteries and veins with the umbilical vein producing the largest quantity of 6KPGF. Thus, immunohistochemistry and ex vivo capacitance studies suggest that there is a differential distribution of 6KPGF in human umbilical arteries and veins.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Immunohistochemical localization of apolipoproteins A-I and B in human carotid arteries.

Decreased plasma levels of apolipoprotein A-I (apo A-I) and increased plasma levels of apolipoprotein B (apo B) have been shown to correlate with increased risk of atherosclerosis. While many studies have investigated the plasma levels of these apolipoproteins with regard to their value as predictors of cardiovascular disease, comparatively little is known about their precise tissue localization in atherosclerotic plaques. The purpose of this study was to determine the tissue localization of apo A-I and apo B in atherosclerotic segments of human carotid arteries through the use of immunohistochemical techniques. With tissue samples obtained from surgery and autopsy, apo A-I and apo B were found to be present in atherosclerotic plaques and absent in normal arterial tissue. In the plaques, both apo A-I and apo B were found extracellularly, primarily in the lipid core, but also in connective tissue. In addition, both apo A-I and apo B were found intracellularly in foam cells. This similar intracellular and extracellular distribution of apo A-I and apo B was unexpected, in view of their differing associations with atherosclerosis.

Apolipoprotein A-I↗
PubMed1987

Immunohistochemical localization of procainamide in normal, ischemic, and necrotic canine myocardium during acute experimental myocardial infarction.

This report represents the first application of immunohistochemical methods for localizing an exogenously administered drug. Intravenously administered procainamide was localized in normal, ischemic, and necrotic myocardium in 23 dogs. Rabbit antiprocainamide antibodies were used in an avidin-biotin-peroxidase complex staining method. Normal myocardium demonstrated diffusely positive immunostaining for procainamide, as did the cardiac conduction system and vascular endothelial cells. Necrotic myocardium demonstrated markedly reduced to absent immunostaining. By contrast, in regions of myocardial ischemia without necrosis, immunostaining for procainamide was similar to that in the normal myocardium. Procainamide myocardial tissue levels were reduced in necrotic and ischemic zones compared to normal (p less than 0.05) only in those animals in which procainamide was administered after rather than before the onset of coronary occlusion. The demonstration of the absence of drug binding in the necrotic cells suggests that myocardial tissue levels or radiolabelled assessment of drug distribution can be misleading when nonhomogeneous tissue is sampled. The immunohistochemical technique provides additional information about the regional and cellular distribution of procainamide that is complementary to the information obtainable by radiolabelling microspheres and from biochemical assays.

Animals↗
PubMed1987

Nonbacterial thrombotic endocarditis: a review.

The entity of NBTE is reviewed in this article. Historic aspects, epidemiology, and pathogenesis are discussed. The clinicopathologic findings are emphasized as well as the potential for antemortem diagnosis and therapy. NBTE is diagnosed infrequently before death. Clinical suspicion is aroused in patients with an underlying process such as malignancy, DIC, or a spectrum of other diseases and evidence of pulmonary and/or systemic embolization. Systemic infection must be excluded. Two-dimensional echocardiography can be utilized to confirm the diagnosis. Anticoagulation therapy with heparin may prevent embolization.

Endocarditis↗
PubMed1987

Cellular electrophysiologic characteristics of surviving subendocardial fibers in chronically infarcted right ventricular myocardium susceptible to inducible sustained ventricular tachycardia.

Permanent occlusion of the right coronary artery (RCA) is associated with inducible sustained ventricular tachyarrhythmias (VT) during days 3 to 10 post RCA occlusion period in the conscious dog; VT could no longer be induced beyond this post occlusion period. The aims of the present study were to determine if subendocardial (SE) fibers in the infarcted right ventricle (RVI) during both inducible and noninducible phases of VT remain viable, and if so, to characterize their transmembrane potential properties with the microelectrode and to assess their morphologic features. The RCA was occluded in 13 closed-chest anesthetized dogs with intracoronary balloon inflation. In one group (N = 7), the infarcted tissues were isolated during the VT inducible phase and in another group (N = 6) these tissues were isolated during the VT noninducible phase. Resting membrane potential, action potential amplitude, maximum upstroke velocity, and action potential duration of the surviving SE Purkinje fibers (PF) and ventricular muscle (VM) in the IZ (first layer) were not significantly different in the two groups. Conduction velocity for both basic and premature stimuli from the base to the apex were similar in the two groups. Rapid stimulation at cycle lengths of 300 to 200 msec failed to induce triggering of automatic activity in the two groups. Electron microscopy of SEPF in the IZ showed a drastic reduction in cytosolic lipid droplet accumulation when compared to 24-hour-old infarct. We conclude that: (1) SEPF and VM network in the infarct zone remain electrically viable during the chronic phase of RVI; (2) transmembrane potential properties of this fiber network remain constant and independent of temporal changes of VT inductibility; and (3) ultrastructural improvement of this fiber network suggests an evolution toward normalcy.

Action Potentials↗
PubMed1987

Thrombosed, ruptured atheromatous plaques in saphenous vein coronary artery bypass grafts: ten years' experience.

During the past decade the number of patients undergoing saphenous vein coronary artery bypass grafting (CABG) has increased worldwide. With a rate of late graft occlusion approximating 4% each year, the number of patients at risk for late graft occlusion continues to increase. Whereas in 1976 only 0.8% of the CABGs performed at our institution were reoperations for occluded grafts, by 1985 repeat procedures comprised 12.4% of the CABGs performed. Excised, occluded saphenous vein grafts from 52 of 119 (44%) of these patients showed thrombosis superimposed on ruptured atheromatous plaques. Ten autopsy patients showed similar lesions in their occluded grafts. The lesion was present in grafts excised as early as 3 years and as late as 14 years after bypass surgery; most occurred 5 to 10 years after implantation. Neither age at first bypass, sex, nor coronary artery bypassed permitted prediction of the occurrence of the lesion. Thrombosed, ruptured atheromatous plaque is a common, clinically significant mechanism of late graft occlusion. It is associated with recurrent symptoms that necessitate repeat revascularization and may result in death. The lesion may also be amenable to thrombolytic therapy, angioplasty, or both.

Acute Disease↗