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Biomedical subjects

A Farb

Publications and source records attributed to A Farb.

At least 109 records · Page 6Linked to original sources
PubMed1991

Limitation of no reflow injury by blood-free reperfusion with oxygenated perfluorochemical (Fluosol-DA 20%).

This study was designed to assess the effects of blood-free reperfusion with oxygenated or unoxygenated intracoronary perfluorochemical (Fluosol-DA 20%) on myocardial perfusion and to determine its mechanism or mechanisms of limiting no reflow. Twenty-four dogs underwent 90 min of coronary occlusion followed by 210 min of reperfusion and were randomized to either: 1) blood-free reperfusion with intracoronary oxygenated perfluorochemical (20 ml/kg per min) for 20 min followed by blood reperfusion (n = 8); 2) intracoronary unoxygenated perfluorochemical administered as in those treated with oxygenated perfluorochemical (n = 8); and 3) blood reperfusion alone (control) (n = 8). Regional myocardial blood flow was serially determined and global myocardial perfusion was assessed by an intravenous injection of the fluorescent dye (thioflavin-S). Quantitative studies were performed to determine neutrophil infiltration and extent of endothelial injury. Hemodynamic variables were similar in all groups. The zone of impaired perfusion (thioflavin negative), expressed as a percent of the left ventricle, averaged 10 +/- 2%, 6 +/- 2% and 3 +/- 1%, in control and unoxygenated and oxygenated perfluorochemical groups, respectively (control versus oxygenated perfluorochemical p less than 0.004). The reduction in thioflavin-negative area with oxygenated perfluorochemical was associated with a notable recovery of endocardial blood flow (0.97 +/- 0.22 vs. control 0.39 +/- 0.08 ml/min per g; p less than 0.04) at 210 min of reperfusion. The number of capillaries plugged by neutrophils (per 200 capillaries) in thioflavin-negative areas was similar with both oxygenated (5.9 +/- 1.4) and unoxygenated perfluorochemical (5.4 +/- 0.8) treatment and was significantly less than that with the control group (18.9 +/- 3.2, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serial sectioning and multiple level examination of endomyocardial biopsies for the diagnosis of myocarditis.

To determine if serial sectioning and multiple level evaluation increase the sensitivity of endomyocardial biopsy for the detection of myocarditis, we prospectively studied all diagnostic endomyocardial biopsies between 1986 and 1989. Biopsies were embedded in paraffin, serially sectioned, and every 4-microns section was mounted in ribbons on glass slides. Every fifth slide was stained with hematoxylin and eosin and examined for myocarditis by the Dallas criteria (myocyte necrosis and inflammatory cells). Of a total of 153 biopsies, 20 cases (13%) were diagnostic of myocarditis on at least one section. Four biopsies (25%) were positive at slide Level 1, and 15 (75%) by slide Level 5; in five cases (25%), diagnostic foci were present only at or after slide Level 10. Multiple levels should be performed in the histologic evaluation of endomyocardial biopsies to increase the sensitivity of endomyocardial biopsy in the evaluation of myocarditis.

Biopsy↗
PubMed1991

Right ventricular dysplasia associated with sudden death in young adults.

The frequency of right ventricular dysplasia (RVD) in an autopsy series of young persons with sudden cardiac death in the United States has not been previously reported. We reviewed the autopsies from cases of sudden cardiac deaths in young adults in the state of Maryland and noted three cases of RVD among 547 cardiac deaths (0.55%). These three cases of RVD in young adults and three additional cases from our file are presented. Their ages ranged from 19 to 28 yr, and there were five males and one female. Five deaths occurred during strenuous exercise while the sixth was unwitnessed. Three of these cases had a documented history of arrhythmias and 1 had palpitations. In each case, autopsy revealed right ventricular dilatation with partial absence of the myocardium and extensive fatty infiltrates with and without fibrosis. In four cases, collections of chronic lymphocytic infiltrates were seen, of which two had associated myocyte necrosis. In one patient, the disease was familial, while in the remaining five it was sporadic, suggesting a nongenetic cause.

Adult↗
PubMed1990

Day-to-day variability of voltage measurements used in electrocardiographic criteria for left ventricular hypertrophy.

Although electrocardiographic (ECG) voltage can be used to estimate left ventricular mass, day-to-day variability of voltage combinations used for this purpose must be established before ECG changes are taken as evidence of progression or regression of hypertrophy. Accordingly, serial ECGs (mean 8 days apart), derived from 10 s samples digitized at 250 Hz, were examined in 78 patients with no intercurrent change in clinical status. The coefficient of variation was calculated as 1 SD of the difference between paired voltage measurements, divided by the average mean value. Coefficient of variation for single leads was 22.3% for SV1, 27.0% for RV5 or RV6, 27.1% for RaVL and 34.7% for SV3. Coefficient of variation was lower for voltage combinations than for individual lead measurements: 18.5% for Sokolow-Lyon voltage (SV1 + RV5 or RV6), 22.3% for Gubner-Ungerleider voltage (R1 + S3) and 24.8% for Cornell voltage (RaVL + SV3). Serial reclassification due to variation above and below standard criteria for left ventricular hypertrophy occurred in only 3% of patients for Sokolow-Lyon voltage and 4% of patients for Cornell voltage in this group. Minute to minute reproducibility of voltage was assessed with electrodes in place in a separate group of 26 patients, and the coefficient of variation was 2.6% for Sokolow-Lyon voltage, 5.9% for Gubner-Ungerleider voltage and 2.9% for Cornell voltage. These data indicate that serial variability of computer-measured ECG voltage combinations is high, due primarily to changes in lead placement and body position, but less than the variability of computer-measured voltage in individual leads.

Adult↗
PubMed1990

Dose-dependent reduction of myocardial infarct size with the perfluorochemical Fluosol-DA.

The perfluorochemical Fluosol-DA has been shown to reduce infarct size. However, the dose-response relationship of the agent is unknown. Because perfluorochemicals (PFC) can potentially saturate the reticuloendothelial system and decrease carbon clearance as well as cause a transient elevation in liver enzymes, the present study was conducted to determine the lowest effective dose. New Zealand White rabbits (n = 73) were randomly selected prior to infarction to receive 10, 15, 20, 25, or 30 ml/kg PFC or an equivalent volume of 5% dextran (control) intravenously. Animals underwent 30 minutes of coronary artery occlusion with PFC or dextran infused over a 30-minute period starting at 20 minutes into the occlusion. Animals were put to death at 24 hours and infarct size was determined histologically and quantitated by computerized planimetry. Neutrophil infiltration into the ischemic myocardium was evaluated semiquantitatively. No hemodynamic differences were noted within groups. Infarct size was similar to that of controls in animals treated with 10 or 15 ml/kg PFC. Significant infarct size reduction, however, was noted in animals treated with 20, 25, and 30 ml/kg PFC versus controls; (p = 0.05, 0.04, and 0.02, respectively). Maximal infarct size reduction was seen with 30 ml/kg PFC (35%). Neutrophil infiltration was significantly decreased in all groups treated with PFC. These results show that intravenous Fluosol-DA significantly reduces infarct size at a minimal dose of 20 ml/kg.

Animals↗
PubMed1990

Plaque morphology and pathologic changes in arteries from patients dying after coronary balloon angioplasty.

Morphologic correlates of pathologic success or failure were studied at autopsy in 28 patients with 40 coronary arteries that had been subjected to balloon angioplasty. The presence of the following histologic features was evaluated: plaque concentricity or eccentricity, calcification, fibrous or fibropultaceous plaque, medial disruption, luminal thrombus and inflammation. Angioplasty was considered successful (residual cross-sectional luminal area greater than 25%) on pathologic examination in 14 arteries and unsuccessful in 26 arteries. Eccentric plaques were more likely to be successfully dilated than were concentric lesions (p less than 0.05). Six (50%) of 12 fibropultaceous plaques were successfully dilated compared with only 8 (29%) of 28 fibrous plaques. Moderate to severe calcification did not preclude morphologic success. Medial stretching or dissection, or both, was more often associated with a successful result. Thus, plaque morphology may be an important determinant of pathologic outcome after coronary angioplasty.

Aged↗
PubMed1990

Sudden cardiac death during exercise in a weight lifter using anabolic androgenic steroids: pathological and toxicological findings.

A 21-year-old, previously healthy weight lifter collapsed during a bench press workout. He had taken anabolic androgenic steroids parenterally for the previous several months. Pertinent autopsy findings included marked cardiac and renal hypertrophy and hepatosplenomegaly, with regional myocardial fibrosis and focal myocardial necrosis. Nandrolone (19-nor-testosterone) metabolites were identified in postmortem urine. The possible etiologies of the cardiac findings are discussed.

Adult↗
PubMed1989

Valve injury and repair in balloon aortic valvuloplasty.

Aortic valves 0.5, and 4.5 months after successful percutaneous balloon aortic valvuloplasty (BAV) were examined. BAV caused macroscopic and microscopic fractures in calcific deposits. An inflammatory response was identified that may lead to valvular scarring. This process may be an important factor in the development of restenosis after BAV.

Aged↗
PubMedDate not supplied

Sudden cardiac death.

The rate of cardiac deaths that are sudden is approximately 50%, and decreases with age. The causes of sudden cardiac death are diverse, and are a function of age. In children and adolescents, coronary anomalies, hypertrophic cardiomyopathy and myocarditis are frequent substrates for lethal arrhythmias; in adults, coronary atherosclerosis and acquired forms of cardiomyopathy are the most common findings at autopsies of sudden cardiac death. This review focuses on coronary causes of sudden cardiac death, especially congenital coronary artery anomalies, which result in sudden death almost exclusively in adults younger than age 35, and coronary thrombosis. The most lethal coronary artery anomaly is the left coronary artery arising from the right sinus of Valsalva; this anomaly often results in fatal arrhythmias, often with exercise. The right coronary artery arising from the left sinus of Valsalva may also be lethal in adolescents and young adults, but, unlike the anomalous left, is more often an incidental finding at autopsy. Approximately 60% of sudden coronary death is caused by coronary thrombosis, the rest die with severe coronary disease in the absence of thrombosis. The two major substrates of coronary thrombosis are plaque rupture and plaque erosion, and are not only different pathologically, but are seen in patients with divergent risk factor profiles. Plaque rupture is the most common cause of fatal coronary thrombus, and is characterized by necrotic core with a thin fibrous cap, infiltrated by macrophages. The factors that result in plaque instability and rupture are largely unknown, and are under intense scrutiny; morphologic studies have identified serum lipid abnormalities as a key risk factor in the development of plaque rupture. Plaque erosion, in contrast to plaque rupture, is seen in younger men and women, is not associated with lipid abnormalities, and does not result from exposure of the lipid core to the lumen. The heterogeneity of the atherosclerotic plaque and the diverse mechanics of plaque progression and thrombosis have only been relatively recently explored, and are largely elucidated by autopsy studies of victims of sudden coronary death.

Coronary Artery Disease↗
PubMedDate not supplied

The degree of neointimal formation after stent placement in atherosclerotic rabbit iliac arteries is dependent on the underlying plaque.

The purpose of this study was to determine the effects of stent placement on the underlying arterial morphology and the relations of stent-vessel wall interactions with subsequent neointimal formation in an atherosclerotic artery. Seven New Zealand White rabbits with experimentally induced atherosclerosis underwent balloon angioplasty (n = 7) and stent placement after balloon angioplasty (n = 7) in the iliac arteries. Histologic analysis of the treated arteries was performed at 28 days to assess device interactions with the artery and the pattern of the neointimal response. The area within the external elastic lamina of the stented vessels was 66% greater than the arteries with balloon angioplasty alone (p = 0.001) which contributed to a significantly greater late lumen area (3.33 +/- 0.51 mm2 versus 1.33 +/- 0.20 mm2, p = 0.0028). Neointimal thickness was measured at 220 stent wire sites from 21 sections of stented arteries of which 139 (63%) had underlying plaque and 81 (37%) were adjacent to normal media. Rupture of the internal elastic lamina (IEL) occurred at only 9 (11%) of the 81 stent wire sites over normal media. The mean neointimal thickness was 0.16 +/- 0.01 mm lor all stent wire sites. The neointimal thickness was greater at the stent wire sites with underlying plaque (0.23 +/- 0.01 min) than at the stent wire sites adjacent to normal media (0.08 +/- 0.01 mm) or at sites with rupture of the internal elastic lamina (0.16 +/- 0.02 mm, p = 0.0001). The degree of neointimal formation within the stents strongly correlated with the area of the underlying atherosclerotic plaque (r = 0.76, p = 0.0007) and the extent of plaque or medial compression by the struts (r = 0.90, p = 0.006). The present study characterizes stent interactions in a model commonly employed to evaluate novel therapies for the prevention of restenosis. The neointimal response was influenced by the local arterial morphology and correlated with the extent of plaque or medial compression by the stent. These data may be useful for future studies in this model and understanding the mechanism of in-stent restenosis.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

Local arterial responses to 32P beta-emitting stents.

PURPOSE: 32P beta-emitting stents reduce neointimal growth in rabbit iliac arteries for at least 12 months after deployment but are associated with incomplete healing. The aim of this study was to quantitate arterial cellularity, with emphasis on the inflammatory response following radioactive stenting. METHODS: 32P beta-emitting stents were placed in rabbit iliac arteries and analyzed at 3 months (6 and 24 microCi), and 6 and 12 months (6, 24, and 48 microCi). Arterial cellular proliferation and cell densities of smooth muscle cells (SMC), mononuclear cells (macrophages and lymphocytes), and neutrophils (PMN) were determined. RESULTS: Total intimal cell density was greatest in control stents at all three time points, composed mostly of SMCs. SMC density associated with radioactive stents increased from 3 to 12 months but was significantly less than control nonradioactive stents. There was a 4-fold increase in cellular proliferation in the 24 and 48 microCi group vs. control stents. In the media, SMC density of radioactive stent groups was significantly reduced vs. control stents at all three time points, for all three activities. At 3, 6 and 12 months, there was a dose-dependent increase in intimal inflammatory cell density, which consisted mostly of macrophages. For 6-microCi stents inflammation peaked at 3 months and decreased thereafter. Inflammation for 24-microCi stents peaked at 6 months and then decreased at 12 months. Inflammation associated with 48-microCi stents remained high at 6 and 12 months. Focal atherosclerotic change was seen in 11% of stents in the 24-microCi group, and 37% and 50% in the 48-microCi group at 6 and 12 months, respectively. CONCLUSION: Intimal SMC density remains suppressed out to 12 months after placement of 32P beta-emitting stents. However, inflammation and cell proliferation remain increased and may potentially result in greater neointimal formation over time.

Animals↗
PubMedDate not supplied

Pathology of radiation-induced coronary artery disease in human and pig.

PURPOSE: External beam mediastinal radiation-induced accelerated coronary atherosclerotic heart disease in humans has been recognized, especially when the condition occurs in young persons. The purpose of the present study was to compare external beam radiation-induced accelerated coronary atherosclerosis in humans with that seen in the pig coronary arteries following radioactive stent placement. METHODS: A literature review of radiation-induced coronary artery disease was performed. In addition, clinical records and coronary histology from the Armed Forces Institute of Pathology Registry were reviewed from patients who had received external beam radiation for mediastinal malignancies. Coronary arteries from pigs that had radioactive coronary stent placement were evaluated from our stent pathology laboratory and analyzed for comparison with the human disease. RESULTS: In humans, the characteristics of the intimal plaque in accelerated atherosclerosis postradiation therapy were similar to that seen in typical atherosclerotic coronary disease in the absence of radiation therapy. However, medial thinning and adventitial fibrosis were the distinguishing pathologic arterial changes secondary to radiation seen in humans. Radioactive stent placement in pig coronary arteries produced similar changes to that observed in humans post-external beam radiation, consisting of medial injury and adventitial thickening accompanied by intimal foam cell collections, calcification, and necrotic core formation containing cholesterol clefts resulting in severe luminal narrowing. CONCLUSIONS: Radiation, delivered via external beam or radioactive stent, induces changes of intimal atherosclerosis with medial thinning and adventitial scarring in human and pig. Therefore, pending completion of long-term clinical studies, caution should be exercised before the widespread use of brachytherapy is advocated for the treatment and prevention of coronary restenosis.

Animals↗
PubMedDate not supplied

Technetium-99m glucarate uptake in a swine model of limited flow plus increased demand.

BACKGROUND: Glucarate is a 6-carbon dicarboxylic acid shown to be taken up by necrotic myocytes, binding to nuclear histones in animal models of coronary occlusion, resulting in infarction. This study investigated glucarate uptake in a model of severe ischemia. METHODS AND RESULTS: Thirty-five experiments were performed, in which a catheter-mounted stenosis (reducing lumen dimensions by 80%) was placed in the left anterior descending coronary artery (LAD) of an anesthetized, instrumented domestic swine and technetium-99m glucarate (GLU) was injected during the last minute of 5 minutes of pacing. Hemodynamic and blood flow measurements were performed at control, during pacing, and during recovery. The animals were killed; their hearts were stained with fluorescein dye and triphenyl tetrazolium chloride (TTC). Electron micography (EM; n = 6) and cell centrifugation (n = 7) were also performed. On the basis of net lactate production and severe blood flow reduction in the risk region (RR), ischemia with pacing developed in 25 animals. Fifteen of 25 animals showed tracer uptake in the RR on in vivo and ex vivo imaging (scan positive), and 10 were scan negative in the RR. Endocardial blood flow in the RR during pacing was 0.28+/-0.16 mL/g/min for scan-positive and 0.30+/-0.17 mL/g/min for scan-negative experiments (P = not significant [NS]). Transmyocardial net lactate extraction during pacing was -63%+/-44% for scan-positive and -53%+/-60% for scan-negative experiments (P = NS). Control and recovery heart rates were higher in scan-positive experiments (108+/-14 vs. 92+/-17, and 125+/-24 vs. 104+/-18, P<.02). Lactate extraction was lower during control and recovery in scan-positive animals (2+/-29 vs. 30+/-19, P = .03). Scan-positive animals had a more proximal stenosis position. Minimal necrosis was documented by means of TTC negative staining in 8 of 15 scan-positive experiments (comprising 10%+/-4.3% of RR area). EM or cell fractionation was performed in 5 of the 7 remaining scan-positive and TTC-positive hearts, and in those 5 experiments, necrosis was documented by means of EM in 2 and by means of cell fractionation in 3. CONCLUSIONS: Uptake of Tc-99m glucarate was seen in the RR in a swine model of ischemia severe enough to produce myocyte injury and early cell death.

Animals↗
PubMedDate not supplied

Pathology of acute and chronic coronary stenting in humans.

BACKGROUND: Despite the increasing use of stents, few reports have described human coronary artery morphology early and late after stenting. METHODS AND RESULTS: Histology was performed on 55 stents in 35 coronary vessels (32 native arteries and 3 vein grafts) from 32 patients. The mean duration of stent placement was 39+/-82 days. Fibrin, platelets, and neutrophils were associated with stent struts </=11 days after deployment. In stents implanted for </=3 days, only 3% of struts in contact with fibrous plaque had >20 associated inflammatory cells compared with 44% of struts embedded in a lipid core and 36% of struts in contact with damaged media (P<0.001). Neointimal growth determined late histological success, and increased neointimal growth correlated with increased stent size relative to the proximal reference lumen area. Neointimal thickness was greater for struts associated with medial damage than struts in contact with plaque (P<0.0001) or intact media (P<0.0001). When matched for time since treatment, neointimal cell density in stented arteries was similar to that in unstented arteries that had undergone balloon angioplasty and showed similar proteoglycan deposition. CONCLUSIONS: Morphology after coronary stenting demonstrates early thrombus formation and acute inflammation followed by neointimal growth. Medial injury and lipid core penetration by struts result in increased inflammation. Neointima increases as the ratio of stent area to reference lumen area increases. Deployment strategies that reduce medial damage and avoid stent oversizing may lower the frequency of in-stent restenosis.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

Comparative pathology: radiation-induced coronary artery disease in man and animals.

The occurrence of coronary artery disease following mediastinal radiation for malignancies has long been debated. However, the development of coronary pathology in young individuals following radiation who lack risk factors for atherosclerosis is highly suggestive of a cause-and-effect relationship. By far the most convincing pathologic changes are adventitial scarring and medial atrophy with severe intimal atherosclerotic disease consisting of necrotic core, fibrous tissue, and calcification. Initial clinical studies in patients with coronary atherosclerosis treated with intraluminal radiation following stenting hold great promise in the treatment and prevention of restenosis. There are little or no data, however, on long-term effects of intra-coronary radiation therapy in man. Therefore, it may be important to study the chronic effects of radiation in animal models in order to predict what is likely to occur in humans. We evaluated the effects of varying doses (0.15-23.0 microCi of 32P) of beta-particle-emitting radioactive stents in pig coronary arteries at 1 and 6 months. At 1 month, there were dose-dependent changes in the morphology of the intima and media. High activities (>3 microCi) caused medial necrosis with fibrin deposition in the media and intima, with interspersed red cells most marked in regions surrounding the stent struts. Only rare smooth muscle cells (SMCs) and inflammatory cells were seen away from the stent struts. In the intermediate (1 microCi) stent activity group, the neointima was expanded by SMCs and a proteoglycan-rich matrix with focal endothelialization of the luminal surface. Neovascular capillaries and extravascular red cells were present adjacent to stent struts. At low activities (<0.5 microCi), the neointima was significantly smaller than control stents and consisted of SMCs and matrix with complete endothelialization of the luminal surface. The neointimal cell density of the media and intima decreased with increasing doses of radiation. In pigs 6 months after radioactive stenting (activities ranging from 0.5-12 microCi 32P), >3.0 microCi radioactive stents induced marked neointimal thickening, with changes similar to atherosclerosis, consisting of necrotic debris containing cholesterol clefts surrounded by macrophage collections, fibrosis, and focal calcification. There was increased adventitial thickening in the radiated vs non-radiated arteries. The intermediate stent activity (1.0 microCi) also showed greater neointimal thickening (vs control stents) and consisted mostly of SMCs in a proteoglycan-rich matrix. At <1.0 microCi, there were minimal differences seen between radiated and control non-radiated stented arteries. The media was unevenly injured in all stent activities and varied from less than to significantly greater than controls. These data suggest that radiation-induced coronary atherosclerosis seen in man is partially simulated in normal porcine coronary arteries 6 months following high-dose beta-particle-emitting radioactive stent placement. There is greater fibrosis and thickness of the adventitia and focal attenuation of the media in man and severe luminal narrowing in pig coronary arteries treated with high doses of radiation. Only long-term clinical follow up and careful autopsy studies will determine if endoluminal or intra-arterial radiation is a viable means of reducing restenosis in man.

Animals↗