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Biomedical subjects

B H Annex

Publications and source records attributed to B H Annex.

31 records · Page 2Linked to original sources
PubMed1998

Induction and maintenance of increased VEGF protein by chronic motor nerve stimulation in skeletal muscle.

Vascular endothelial growth factor (VEGF) causes endothelial cell proliferation in vitro and angiogenesis in vivo. Glycolytic skeletal muscles have a lower capillary density than oxidative muscles but can increase their capillary density and convert to a more oxidative phenotype when subject to chronic motor nerve stimulation (CMNS). We used Western analysis and immunohistochemical techniques to examine VEGF protein in a rabbit CMNS model of glycolytic skeletal muscle and in muscles with innate glycolytic versus oxidative phenotypes. VEGF protein per gram of total protein was increased in stimulated vs. control muscles 2.9 +/- 1.0, 3.6 +/- 1.3, 3.1 +/- 0.5, 4.4 +/- 1.6, and 2.7 +/- 0.3 times after 3 (n = 4), 5 (n = 2), 10 (n = 3), 21 (n = 3), and 56 (n = 2) days, respectively. VEGF protein was increased 3.1 +/- 0.5 times (P < 0.005) before (3, 5, and 10 days) and remained elevated 3.7 +/- 1.0 times (P < 0.05) after (21 and 56 days) the transition to an oxidative phenotype. By immunohistochemistry, VEGF protein was found primarily in the matrix between stimulated muscle fibers but not in the myocytes. In addition, VEGF protein was consistently lower in innate glycolytic compared with oxidative muscles. These findings suggest that VEGF plays a role in the alteration and maintenance of vascular density in mammalian skeletal muscles.

Animals↗
PubMed1997

Efficient adenoviral gene transfer to early venous bypass grafts: comparison with native vessels.

OBJECTIVES: Gene therapy may provide new approaches to reduce vein graft failure following coronary or peripheral bypass surgery. The aim of this study was to investigate the relative efficacy of intraoperative adenoviral gene transfer to vein grafts, comparing transgene expression in vein grafts with that in matched native vessels in the same animal. In addition, we assessed the impact of bypass grafting on the cellular targets of gene transfer. METHODS: New Zealand White rabbits underwent interposition bypass grafting of the carotid artery, using the ipsilateral external jugular vein, which was infected with an adenovirus expressing beta-galactosidase immediately prior to bypass grafting (n = 16). The contralateral native jugular vein (n = 16) and carotid artery (n = 8) were infected concurrently with the same adenoviral preparation. After 3, 7 or 14 days, beta-galactosidase protein expression was quantified by ELISA, and specific cell types expressing beta-galactosidase were identified by X-Gal staining and by immunohistochemistry. RESULTS: After 3 days, endothelial cells were efficiently transduced in all vessels; medial smooth muscle cells were transduced infrequently. In contrast to jugular veins after gene transfer, endothelium in vein grafts showed expression of VCAM-1 and ICAM-1, and intense inflammation with CD18+ leukocytes. Transgene expression in vein grafts at day 3 was maintained at levels approximately 50% of that in ungrafted jugular veins, but continued to decrease through day 7. CONCLUSIONS: Although vascular injury in early venous bypass grafts reduces gene transfer efficacy, significant transgene expression is maintained for at least 7 days. These findings have important implications for intraoperative gene transfer strategies in vein grafts.

Adenoviridae↗
PubMed1997

Admission prediction of expected final myocardial infarct size using weighted ST-segment, Q wave, and T wave measurements.

Formulas for predicting final acute myocardial infarction (MI) size from ST-segment deviation on an initial electrocardiogram were proposed by Aldrich et al. for anterior and inferior infarct locations. This study of 529 patients who did not receive thrombolytic therapy was performed to determine the effectiveness of the Aldrich formulas for predicting final QRS MI size; to propose new formulas for predicting final MI size using ST-segment deviation, Q wave, and T wave information in a development population of 322 patients; and to evaluate the new formulas in a randomly selected population of 207 patients. The Aldrich formulas achieved correlations with final infarct size of r = .40 for anterior and r = .43 for inferior MI locations in the present population which are weaker than those previously reported. Formulas that consider electrocardiographic parameters in addition to ST-segment deviation were proposed for both anterior and inferior final MI size. In the test set of 207 patients, these models explained 16.9% and 15.2% of the variation in final MI size for anterior and inferior locations respectively. They may prove useful in assessing the extent of myocardial salvage where interventions are to be tested.

Electrocardiography↗
PubMed1997

Coronary angioscopy. Clinical applications.

Percutaneous coronary angioscopy is an invaluable alternative imaging modality that can not be used routinely in the interventional cardiac catheterization laboratory. The major value of angioscopy lies in its ability to determine safely, quickly, and accurately intraluminal morphologies before and after coronary interventions. The results from angioscopy can then be used to target more specific treatment strategies, given the vast array of interventional treatment strategies available. Percutaneous coronary angioscopy, however, requires meticulous attention for the proper preparation and use of the angioscope to minimize the potential risks associated with the imaging procedure.

Angioscopy↗
PubMed1997

Modulation of tissue factor protein expression in experimental venous bypass grafts.

Vein graft failure is a major limitation of coronary artery and peripheral vascular surgery. Tissue factor (TF), a transmembrane glycoprotein, generates thrombin by initiating the extrinsic coagulation cascade and plays a major role in the response to arterial injury. This study was designed to examine changes in TF protein expression in response to venous bypass grafting. New Zealand White rabbits underwent interposition bypass grafting of the common carotid artery via the ipsilateral external jugular vein. The contralateral control jugular veins (n = 6), early vein grafts (1 or 3 days after grafting, n = 18), and late vein grafts (14 or 28 days after grafting, n = 8) were examined by immunohistochemistry. The presence or absence of TF immunostaining in the intima was assessed in each vessel quadrant. In control veins, intimal TF staining was present in 5 of 24 vessel quadrants. In early vein grafts, TF staining was markedly increased in the intima (72 of 72 quadrants, P < .001 vs control veins), and TF immunostaining colocalized with CD18-positive leukocytes but not with endothelial cells, vascular smooth muscle cells, or RAM11-positive macrophages. In late vein grafts with intimal hyperplasia, TF expression was low or absent in the intima (6 of 32 quadrants, P < .001 vs early vein grafts; P = NS vs control veins), although medial smooth muscle cells expressed TF. Marked changes in TF expression occur in vein grafts. In early vein grafts, TF protein was greatly increased in the intima for at least 3 days and was associated with CD18-positive leukocytes. In late vein grafts with intimal hyperplasia, however, TF protein was not seen in the intima. These findings may have important implications for the development of therapeutic strategies to limit vein graft failure.

Animals↗
PubMed1997

Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary infusion: a potential approach to myocardial repair.

Myocardial repair after injury is limited because the adult heart cannot regenerate. We propose using autologous skeletal muscle cells (myoblasts) as a source of reserve cells for repair of regions of damaged myocardium. This report examines two potential methods for the transfer of cells to the myocardium: selective coronary catheterization, and myoblast infusion or myoblast injection directly into the left ventricular wall. Autologous, primary rabbit skeletal myoblasts were harvested, were transduced ex vivo with adenoviruses expressing the Escherichia coli beta-galactosidase (beta-gal) gene, and were infused selectively into the coronary circulation or injected directly into the myocardial wall. After either delivery method, beta-gal expression was detectable at the earliest times examined (3 days) and persisted for several weeks. The method of delivery influenced the spatial pattern of beta-gal expression. After direct injection, a localized concentration of myoblasts that decreased with distance from the injection site was visible primarily in the myocardial layer of the ventricle, although occasional staining could be detected in other layers. After coronary infusion, discrete punctate or linear foci of beta-gal expression were found throughout the distribution of the left coronary circulation in all cardiac layers. After infusion or injection, beta-gal-positive cells were seen in direct physical apposition to cardiocytes; interestingly, beta-gal could be detected also in some branched cells with clear cross-striations. Autologous myoblasts survived with no obvious dysrhythmic effects despite their presence in extensive or discrete loci in the myocardium. These observations provide the first evidence that myoblast transfer is possible by catheter-based methods, and they create the basis for studies to investigate the functional consequences of myoblast infusion in damaged heart.

Animals↗
PubMed1995

Differential expression of tissue factor protein in directional atherectomy specimens from patients with stable and unstable coronary syndromes.

BACKGROUND: Tissue factor (TF) is a cell membrane-associated protein that catalyzes the rate-limiting step of the extrinsic coagulation pathway, which is the major source of thrombin production in vivo. To explore the potential role that TF may play in ischemic coronary syndromes, directional coronary atherectomy specimens were tested for the presence of TF protein using immunohistochemical techniques. METHODS AND RESULTS: Frozen sections from atherectomy specimens in 61 patients were examined for TF expression using an IgG murine monoclonal antibody against human TF. Patients were classified according to their admission diagnosis as having either an unstable or a stable coronary syndrome. An unstable coronary syndrome was defined as either angina pectoris occurring at rest or post-myocardial infarction (< 1 week) angina. Stable coronary syndromes included patients with stable, progressive, and new-onset (< 6 weeks) angina without rest pain. TF was detected in 15 (43%) of 35 patients with unstable coronary syndromes versus only 3 (12%) of 26 patients with stable coronary syndromes (odds ratio, 5.7; 95% confidence interval, 1.3 to 24.3; P = .018). Within the subgroup of patients with unstable coronary syndromes, TF was detected in 14 (60%) of 25 patients with de novo lesions versus only 1 (10%) of 10 patients with a restenosis lesion (P < .02). An additional 8 patients with stable coronary syndromes due to a restenosis lesion were also negative for TF. Therefore, the overall incidence of TF expression was only 6% (1 of 18) in restenosis lesions compared with 33% (14 of 43) in de novo lesions (P < .03). CONCLUSIONS: This study provides the first description of TF protein expression in human coronary artery lesions in vivo. Tissue factor was readily detected in de novo lesions in patients with unstable coronary syndromes, suggesting a role for TF in the pathogenesis of this disease process. Conversely, TF was rarely detected in patients with restenosis lesions even if the resulting clinical presentation was an unstable coronary syndrome. These results may have implications for the management of patients with unstable angina from de novo lesions and patients with ischemic symptoms from a restenosis lesion.

Angina Pectoris↗
PubMed1994

Angioscopic guided interventions in a saphenous vein bypass graft.

Intracoronary stents appear promising for treatment of focal vein graft lesions, but their use may be limited by the presence of intraluminal thrombus. This report describes the use of percutaneous coronary angioscopy to identify the presence or absence of intraluminal thrombus and to guide interventional therapy with transluminal extraction coronary atherectomy (TEC) and stenting in a patient with a complex vein graft stenosis.

Atherectomy, Coronary↗
PubMed1994

Transluminal extraction coronary atherectomy.

The TEC is a forward-cutting atherectomy catheter that has the unique potential to excise and aspirate atheroma, especially intraluminal thrombus. This device has been under clinical investigation for more than 6 years and received final marketing approval by the FDA for the treatment of lesions in the coronary vasculature in 1993. In the US TEC Multicenter Registry, the overall clinical and lesion successes were favorable. The success rates were similar for both native coronary vessels and saphenous vein bypass grafts. Importantly, the procedural success rates were maintained even in the presence of several unfavorable angiographic features, such as ostial location, intraluminal thrombus, and total occlusion. Further insights into the mechanisms of action of the TEC were made from studies using percutaneous angioscopy and intravascular ultrasound. Angioscopy clearly demonstrated that the TEC was indeed able to remove intraluminal thrombus, especially loosely adherent red thrombus, in a population of patients with unstable coronary syndromes. However, the TEC frequently leaves behind multiple intimal disruptions which not only create a possible nidus for restenosis but also explain the frequent hazy angiographic appearance of the vessel after TEC atherectomy. As is true for all new interventional devices, the specific niche for the TEC in interventional cardiology will best be determined in randomized clinical trials. There are several areas in which the TEC appears promising. First, this device may have a role in the management of patients with diffusely diseased saphenous vein grafts. Second, the TEC may be an effective primary therapy in lesions with intraluminal thrombus. Treatment with the TEC may then be followed by an adjunctive therapy to maximize the final vessel diameters. Finally, the TEC may be valuable in the treatment of lesions in patients with high-risk unstable coronary syndromes.

Atherectomy, Coronary↗
PubMed1991

Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase mRNA by nerve stimulation.

Tonic contractile activity induces mitochondrial biogenesis in mammalian skeletal muscles, necessitating regulation of both nuclear and mitochondrial genes encoding mitochondrial proteins. In this study we compared the time course of induction of citrate synthase (CS) mRNA, a nuclear gene product, to that of genes encoded by mitochondrial DNA during the adaptive response to indirect nerve stimulation in tibialis anterior muscles of adult rabbits. A CS cDNA probe was prepared from a rabbit heart cDNA library by the polymerase chain reaction using synthetic oligonucleotide primers based on the published sequence of the porcine gene. This cDNA probe hybridized to a single band on Northern blots of total or polyadenylated RNA from adult rabbit tissues. Nerve stimulation for 3 days increased the abundance of CS mRNA relative to total cellular RNA by 2.3 +/- 0.2-fold (mean +/- SE, n = 8; P less than 0.01). In contrast, CS enzyme activity and mitochondrial RNA transcripts were not significantly increased at this time point. However, when nerve stimulation was continued for 21 days, the increases in CS mRNA and mitochondrial RNAs were similar. These results support the hypothesis that genetic signaling mechanisms triggered by neural input are sensed initially within the nucleus and that expression of mitochondrial genes is regulated as a secondary event.

Animals↗
PubMed1990

Mitochondrial DNA structure and expression in specialized subtypes of mammalian striated muscle.

Mitochondrial DNA (mt DNA) in cells of vertebrate organisms can assume an unusual triplex DNA structure known as the displacement loop (D loop). This triplex DNA structure forms when a partially replicated heavy strand of mtDNA (7S mtDNA) remains annealed to the light strand, displacing the native heavy strand in this region. The D-loop region contains the promoters for both heavy- and light-strand transcription as well as the origin of heavy-strand replication. However, the distribution of triplex and duplex forms of mtDNA in relation to respiratory activity of mammalian tissues has not been systematically characterized, and the functional significance of the D-loop structure is unknown. In comparisons of specialized muscle subtypes within the same species and of the same muscle subtype in different species, the relative proportion of D-loop versus duplex forms of mtDNA in striated muscle tissues of several mammalian species demonstrated marked variation, ranging from 1% in glycolytic fast skeletal fibers of the rabbit to 65% in the mouse heart. There was a consistent and direct correlation between the ratio of triplex to duplex forms of mtDNA and the capacity of these tissues for oxidative metabolism. The proportion of D-loop forms likewise correlated directly with mtDNA copy number, mtRNA abundance, and the specific activity of the mtDNA (gamma) polymerase. The D-loop form of mtDNA does not appear to be transcribed at greater efficiency than the duplex form, since the ratio of mtDNA copy number to mtRNA was unrelated to the proportion of triplex mtDNA genomes. However, tissues with a preponderance of D-loop forms tended to express greater levels of cytochrome b mRNA relative to mitochondrial rRNA transcripts, suggesting that the triplex structure may be associated with variations in partial versus full-length transcription of the heavy strand.

Animals↗