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Biomedical subjects

A Farb

Publications and source records attributed to A Farb.

At least 91 records · Page 5Linked to original sources
PubMed1994

Cardiac damage induced by 2-amino-3-methyl-imidazo[4,5-f]quinoline in nonhuman primates.

The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potent hepatocarcinogen in cynomolgus and rhesus monkeys. The finding of high cardiac IQ-DNA adduct levels prompted a histopathological study of perfusion-fixed hearts from 10 tumor-bearing monkeys chronically dosed with IQ at 10 mg/kg or 20 mg/kg 5 days per week for 48-80 months. Two monkeys dosed only with the vehicle for IQ, hydroxypropylcellulose, served as controls. All the monkeys had normal heart weights, and no abnormalities were observed upon gross inspection of the hearts. Microscopically, focal myocardial lesions were observed in 8 of 10 monkeys dosed with IQ. Light microscopic abnormalities included myocyte necrosis with or without chronic inflammatory infiltrates, interstitial fibrosis with myocyte hypertrophy or atrophy, and vasculitis. Electron microscopic findings included disruption of the mitochondrial architecture (i.e., mitochondrial swelling and clearing of matrix densities), myofibrillar loss, disorganization of the normal alignment of sarcomeres, and occasional myocytes showing nuclear hypertrophy or peripheral clumping of the nuclear chromatin. There was some correlation between the cumulative dose of IQ and the extent of the myocardial abnormalities. These findings suggest that chronic exposure to IQ can lead to myocardial damage in monkeys. Although focal and not associated with clinical evidence of heart failure, these abnormalities may represent the initial stages of IQ-induced toxic cardiomyopathy.

Animals↗
PubMed1994

Causes of sudden cardiac death in patients with replacement valves: an autopsy study.

We retrospectively reviewed 52 hearts from patients who had heart valve replacement more than one month prior to death. In 37 cases death was sudden (less than 6 hours after symptoms). These 37 cases were divided as Group I (15 cases, sudden death related to valve prosthesis); and Group II (22 patients, sudden death not related to valve prosthesis). Causes of death in Group I were valve thrombosis (n = 4), embolization of valve thrombi (n = 2), strut fracture (n = 2), anticoagulation-related hemorrhage (n = 2), perivalvular fistula (n = 1) and left ventricular outflow obstruction (n = 1). Causes of death in Group II were presumed arrhythmia in 14, myocardial infarction in six and aortic rupture in two cases. Severe coronary atherosclerosis (> 75% cross-sectional area luminal narrowing) was present in five of 14 cases dying of arrhythmia and in all six cases with myocardial infarction; in the remaining cases, there was marked cardiac hypertrophy (mean weight 728 +/- 177 grams). The mean age (54 +/- 18 vs. 54 +/- 13 years, respectively) was similar in both groups. Seven of 21 deaths after aortic, 6/12 deaths after mitral, 10/25 deaths after mechanical, and 5/11 after porcine valve replacement were secondary to valve complications. The mean left ventricular thickness was 1.7 cm in both groups, the mean left ventricular cavity dimension 2.8 +/- 1.4 cm in Group I vs. 3.5 +/- 1.4 cm in Group II, and the mean heart weight was 550 grams in Group I vs. 734 +/- 211 in Group II (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Early detection and measurement of experimental myocardial infarcts with horseradish peroxidase.

Current methods of experimental infarct size measurement require tissue analysis several hours after the ischemic event. Electron microscopy identifies irreversibly injured myocytes early after ischemia, but cannot be used to measure myocardial infarct size. Horseradish peroxidase (HRP), a tracer protein that permeates the disrupted sarcolemma of injured myocytes, was used to determine infarct size. New Zealand White rabbits (n = 15) were subjected to 30 min coronary artery occlusion and 24 h reperfusion. Prior to euthanasia, HRP was administered intravenously. The hearts were excised, perfused with triphenyl tetrazolium chloride (TTC), and perfusion fixed. A frozen section was cut from left ventricular slices, and the brown HRP reaction product was developed with 3,3'-diaminobenzidine tetrahydrochloride and H2O2. The areas delineated by intramyocyte HRP (as a percent of the left ventricle) closely correlated with infarct size determined by conventional hematoxylin-eosin (H&E) stain and TTC (means +/- S.E.M.): 29.5 +/- 3.0% vs 27.6 +/- 2.9% vs 28.6 +/- 2.6%, respectively. The coefficient of correlation between HRP and H&E was 0.94. This method was tested for early infarct detection in rabbits subjected to 30 min coronary occlusion followed by intravenous injection of HRP and sacrifice. HRP-delineated infarcts measured 21.4 +/- 3.7% of the left ventricle, and electron microscopic examination from ischemic and non-ischemic areas was used to confirm that cells containing HRP were irreversibly injured. Thus, HRP can be used to accurately measure myocardial infarct size in experimental coronary artery occlusion and reperfusion in infarcts as early as 30 min after coronary occlusion or following 24 h of reperfusion.

Animals↗
PubMed1993

Myocardial infarct extension during reperfusion after coronary artery occlusion: pathologic evidence.

OBJECTIVES: The goal of this study was to demonstrate myocardial infarct extension during reperfusion within the same animal. BACKGROUND: Whether myocardial reperfusion can result in the extension of myocardial necrosis remains controversial. The transformation of reversibly injured myocytes into irreversibly damaged cells after reperfusion has been difficult to demonstrate pathologically. METHODS: New Zealand White rabbits (Group I, n = 10) were subjected to 30 min of coronary artery occlusion and 180 min of reperfusion. Horseradish peroxidase, a tracer protein that permeates the sarcolemma of irreversibly injured myocytes, was used to quantitate myocyte necrosis at the beginning of reperfusion. Within the same heart, infarct size was measured after 180 min of reperfusion by triphenyltetrazolium chloride (TTC) staining. In separate experiments to demonstrate the validity of the model, rabbits were subjected to 30 min of coronary occlusion, followed by intravenous infusion of horseradish peroxidase and rapid induction of death (Group II) or 30 min of occlusion, 180 min of reperfusion with horseradish peroxidase administered after 180 min of reperfusion and TTC staining after induced death (Group III). RESULTS: In Group I, infarct size at the onset of reperfusion, delineated by horseradish peroxidase, measured 45.3 +/- 2.8% of the area of risk and was significantly less than TTC-delineated infarct size after 180 min of reperfusion (59.8 +/- 3.3%, p = 0.0002). By electron microscopy, border areas within the ischemic bed demonstrated irreversibly injured horseradish peroxidase-positive myocytes adjacent to irreversibly injured horseradish peroxidase-negative myocytes, suggesting that further cell death occurred during reperfusion. In Group II, infarcts delineated by horseradish peroxidase after 30 min of coronary occlusion were similar in size to infarcts measured by this tracer in Group I. In Group III, infarcts delineated by horseradish peroxidase at 180 min of reperfusion were similar in size to infarcts measured by TTC and similar to TTC-delineated infarcts measured at 180 min of reperfusion in Group I. CONCLUSIONS: These results provide evidence that there is a subset of myocytes in border areas within the ischemic region that are viable at the beginning of reperfusion but subsequently progress to irreversible injury during the reperfusion period.

Animals↗
PubMed1993

Feasibility and drug delivery efficiency of a new balloon angioplasty catheter capable of performing simultaneous local drug delivery.

BACKGROUND: Local drug delivery at angioplasty treatment sites may improve acute and long-term results after angioplasty. A new dual-purpose balloon angioplasty catheter containing intramural channels and exterior pores ('channeled balloon') was designed to allow local drug delivery at low pressure without jet streams during simultaneous balloon angioplasty. METHODS: Acute feasibility studies were performed in normal ex-vivo and in-vivo arteries (three canine arteries and three rabbits with normal iliac arteries), in which 2 ml of marker agents were locally infused at 2 atm during simultaneous angioplasty at 6 atm with the channeled balloon. Histology, radioactive counting, and autoradiography were performed to determine the intramural localization of the delivered markers. The in-vitro efficiency of acute local drug delivery was estimated in seven normal canine arteries by infusing 3H-heparin and radioactive counting. RESULTS: Histology revealed the presence of markers in the inner third of the media in all ex-vivo samples, and markers in all in-vivo iliac arteries except for one, whereas control segments had no intramural staining. Autoradiography documented transmural radioactive granules. Radioactive counts were 40- to 263-fold higher in those locally treated with the radioactive marker agent. Efficiency of the acute local delivery was estimated by dividing the actual counts by the expected counts; it ranged from 24 to 48%. CONCLUSION: This study demonstrates that the channeled balloon is capable of delivering drugs locally at low pressure in adequate concentrations during simultaneous high-pressure balloon angioplasty in normal arteries.

Angioplasty, Balloon, Coronary↗
PubMed1993

Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina. A clue to the mechanism of transformation from the stable to the unstable clinical state.

BACKGROUND: The mechanisms responsible for the transformation of stable angina to unstable angina, a major cause of morbidity and mortality, are commonly believed to be plaque rupture and thrombosis. We determined whether additional mechanisms are operative by analyzing the histopathology and immuno-histopathology of coronary plaques retrieved by directional atherectomy of patients with unstable angina in whom no intraluminal thrombus was demonstrated by angiography. METHODS AND RESULTS: The histological findings of atherectomy specimens from 34 patients with unstable angina were compared with those of 24 patients with postangioplasty restenosis, whose lesions are known to be composed of smooth muscle cells (SMCs), and 10 patients with stable angina, whose lesions contain relatively few SMCs. We also studied the expression of acidic and basic fibroblast growth factors (aFGF and bFGF), whose role in the vascular response to injury has been established. Specimens from unstable angina resembled those from postangioplasty restenosis in regard to SMC abundance (scale, 0 to 3; 1.4 +/- 0.9 versus 1.7 +/- 0.9; P = NS), and both differed from those of stable angina. Thrombus and/or hemorrhage occurred in only 34% of patients with unstable angina (compared with 8% of restenosis patients and in none of stable angina patients). Active lesions (defined as lesions (defined as lesions containing one or more of the following: thrombus, hemorrhage, abundant and disorganized SMCs in the presence of loose connective tissue, or inflammatory infiltrate) were observed in 56% of the unstable angina patients and in 50% of the restenosis patients but in none of the stable angina patients. The expression of aFGF and bFGF was detected in 80% to 100% of unstable angina (n = 11) and restenosis (n = 10) specimens but in only 1 of 5 stable angina specimens. CONCLUSIONS: Microscopic evidence of thrombosis and plaque rupture occurred in only one third of unstable angina patients, selected because they had no angiographic evidence of intracoronary thrombus. Moreover, their lesions resembled those of restenosis patients in regard to SMC abundance, lesion activity, and the expression of aFGF and bFGF. Our findings therefore suggest that an alternative mechanism to plaque rupture and thrombus formation may be operative in the precipitation of unstable angina; namely, in a subset of patients, SMC proliferation may lead to gradual plaque expansion and thereby to lumenal narrowing and unstable angina. Our data also suggest a role for aFGF and bFGF in this process.

Adult↗
PubMed1992

Comparison of cardiac findings in patients with mitral valve prolapse who die suddenly to those who have congestive heart failure from mitral regurgitation and to those with fatal noncardiac conditions.

Sudden death occurs in a small but important subset of patients with mitral valve prolapse (MVP). Clinical criteria for identifying patients at risk for sudden death have been elusive. To determine if certain morphologic characteristics were present in hearts from patients with sudden cardiac death and MVP, autopsy hearts from persons with sudden death and isolated MVP who were previously asymptomatic or had a history of cardiac arrhythmias (n = 27) were compared with (1) hearts from patients with congestive heart failure (CHF) and mitral regurgitation (MR) secondary to MVP (n = 14), and (2) hearts from persons dying from non-cardiac causes in which MVP was an incidental finding (n = 19). Patients who died suddenly were younger than both patients with MR/CHF and incidental cases (37 +/- 10 vs 65 +/- 16 and 58 +/- 21 years, respectively, p less than 0.001). Mitral valve annular circumference, anterior and posterior mitral valve leaflet lengths, posterior mitral valve thickness, and presence and extent of endocardial plaque were greater in hearts from patients with sudden death than hearts from those with incidental MVP. Hearts from patients with MR/CHF weighed significantly more, had greater left and right atrial cavity sizes and left ventricular cavity diameter than hearts from both sudden death and incidental cases.

Age Factors↗
PubMed1992

Causes of sudden death in athletes.

The incidence of sudden death in athletes is low. Some pathologic conditions, such as hypertrophic cardiomyopathy, coronary artery anomalies, and right ventricular dysplasia may predispose to sudden death during exercise in young athletes. In older individuals, exercise may trigger terminal arrhythmias in patients with atherosclerosis. Screening programs for young individuals undertaking athletic regimens are currently recommended only for those with a suggestive clinical or family history. For older individuals, caution should be advised for patients with known or suspected atherosclerotic disease.

Cardiomegaly↗
PubMed1992

Anatomy and pathology of the right ventricle (including acquired tricuspid and pulmonic valve disease).

With the increased availability of various imaging techniques to assess right ventricular structure and function, there has been a greater appreciation of the importance of right ventricular performance in the setting of left ventricular dysfunction as well as intrinsic ventricular diseases. This article discusses the pathology of the right ventricle, tricuspid valve, and pulmonic valve and concentrates on the major acquired and congenital conditions that manifest in an adult population.

Adult↗
PubMed1991

Sports-related and non-sports-related sudden cardiac death in young adults.

Sports-related sudden cardiac deaths were compared with non-sports-related sudden cardiac death in individuals (14 to 40 years old) who were autopsied from 1981 to 1988 at the Maryland Medical Examiner's Office. Thirty-four of 690 total cases of sudden cardiac death were sports-related, which represents 5% of sudden cardiac death in this age group. Causes of death were severe atherosclerosis (nine), hypertrophic cardiomyopathy with asymmetry (eight), coronary artery anomalies (four), idiopathic concentric left ventricular hypertrophy (three), myocarditis (two), arrhythmogenic right ventricle (one), Kawasaki disease (one), and unknown (six); two of the cases with unknown causes had tunnel arteries. Exercise-related deaths were more likely due to hypertrophic cardiomyopathy (p = 0.0007) compared with 102 age-, sex-, and race-matched controls in the non-exercise group; there was no difference in the incidence of severe atherosclerosis (p = 0.4). The mean age of individuals with hypertrophic cardiomyopathy with asymmetry was less than that of those with severe atherosclerosis (24 vs 32 years, p = 0.03). Thus exercise precipitates sudden cardiac death in younger individuals with hypertrophic cardiomyopathy.

Adolescent↗
PubMed1991

Percutaneous transluminal coronary angioplasty guidewire-induced coronary artery dissection without balloon inflation.

A case of arterial dissection of the right coronary artery secondary to angioplasty guidewire manipulation is presented. No balloon inflation was performed. The histologic appearance of the involved arterial segment was similar to that found in the left anterior descending coronary artery, which had undergone successful balloon dilatation. Both arteries demonstrated medial disruption and fibrointimal proliferation. The pathologic features of angioplasty-induced vascular injury may occur with or without balloon inflation.

Aged↗