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Biomedical subjects

B Höfling

Publications and source records attributed to B Höfling.

At least 37 records · Page 2Linked to original sources
PubMed1996

Local photodynamic therapy reduces tissue hyperplasia in an experimental restenosis model.

Local photodynamic therapy may have potential in preventing myointimal hyperplasia after angioplasty. In this study, the effect of photodynamic therapy was evaluated in an experimental model of restenosis. Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries. Animals were randomly allocated to four groups: group 1, unidirectional injury only; group 2, injury followed by local delivery of photosensitizer; group 3, injury followed by local exposure to monochromatic light; and group 4, where injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (photodynamic therapy). Seven, 14 or 21 days after treatment, all experimental vessels were excised, fixed and processed for histology. An inflammatory and myoproliferative response was observed after injury in vessels from groups 1, 2 and 3. In group 4, after injury followed by photodynamic therapy, the myoproliferative response was significantly reduced. Thus, in this study, tissue hyperplasia after unidirectional injury was effectively suppressed by photodynamic therapy.

Animals↗
PubMed1996

[Local drug administration systems, preclinical and clinical use: perspectives and limitations].

Platelet activation, inflammation, recoil, tissue hyperplasia and remodeling are pivotal pathophysiologic factors in acute myocardial ischemia and restenosis development after angioplasty. It has been suggested that short duration of effective drug levels and poor efficiency of systemic drug administration account for the failure of therapy in clinical trials. A rational effective therapy for angina and restenosis should therefore be locally administered at the site of vascular obliteration. Special local drug delivery devices could be used to administer sufficient drug amounts at the site that needs to be treated. Local drug delivery systems using modified balloon systems, stent systems or newly designed catheters have been developed. In experimental studies different effects can be demonstrated by using endoluminal and adventitial substance delivery. Endoluminal application usually resulted in < 1% effective drug delivery in the arterial wall and short lasting deposition. Adventitial deposition led to higher mural concentrations and the drug was detectable therefore up to 21 days. In media and adventitia the maximum is still comparable to the maximum obtained after systemic application. Experimental studies indicate positive therapeutic effects in restenosis models. Feasibility has been proven in clinical studies of unstable angina with anticoagulants or antithrombotics. Further preclinical and preliminary clinical studies are needed to clarify regional drug distribution, regional wash-out, adverse effects and evaluation of long-term therapeutic effects. Recent developments in catheter techniques might enable effective local drug application in angina and restenosis prophylaxis with a reduction in systemic adverse effects.

Administration, Topical↗
PubMed1996

[Directional coronary atherectomy in coronary dissection?].

Significant local dissection at the site of angioplasty remains the most common cause of complications at balloon dilatation. In the past, the only solution was to transfer the patient for emergency coronary artery bypass grafting. Recent improvements in equipment and increasing experience mean that alternative instrumental methods are now available to manage dissection; in particular, by directional atherectomy and stent implantation, thus possibly avoiding surgery. In this article, the use of atherectomy as management for acute local dissection will be discussed, with special reference to the potential difficulties which may be encountered. Data showing that excellent immediate results and good long-term success can be achieved with atherectomy for acute dissection using careful selection criteria will be presented, indicating that atherectomy is a valid alternative instrumental treatment for the management of such dissection.

Aortic Dissection↗
PubMed1995

[Coronary sinus blood flow after intracoronary or intravenous administration of bisoprolol in coronary disease].

OBJECTIVE: To measure changes in haemodynamics and myocardial blood flow after acute intravenous (i.v.) and intracoronary (i.c.) injection of bisoprolol in patients with coronary heart disease. PATIENTS AND METHODS: A prospective, randomized controlled study of 14 patients (12 men, 2 women; mean age 65 [50-73] years) with angio-graphically proven coronary artery stenosis (reduced in lumen of at least 70%) in one or more major vessels. Seven patients received, before balloon angioplasty, either 0.01 mg/kg body weight directly into the coronaries (group 1, infusion through the guiding catheter) or 2.5 mg (group 2, via the sheath). Heart rate and blood pressure were measured before and after bisoprolol injection. Coronary blood flow was measured by the thermodilution method via two indwelling catheters in the coronary sinus. RESULTS: After bisoprolol there was a reduction in heart rate (group 1: from 83/min to 75/min; group 2: from 77/min to 72/min) and blood pressure (group 1: from 137/80 mm Hg to 125/70 mm Hg; group 2: from 135/86 mm Hg to 126/80 mm Hg). Coronary blood flow was lower after i.c. bisoprolol injection than before (group 1: 383 ml/min vs 352 ml/min, but higher after i.v. injection (group 2: 353 ml/min vs 384 ml/min). These differences were statistically not significant. CONCLUSION: While after-load was clearly reduced and myocardial blood flow remained unchanged, bisoprolol improved myocardial oxygen balance. No different effects could be detected after intracoronary vs intravenous application of bisoprolol.

Aged↗
PubMed1995

Dislocation of the rotating cutter during directional coronary atherectomy: a note of caution.

Directional coronary atherectomy (DCA) has received increased attention, especially as a bail-out procedure after failed balloon angioplasty. However, this technique may also be burdened by severe pitfalls. We report a patient with a balloon-resistant left coronary artery lesion subsequently treated with DCA. Despite its over-the-wire guidance, as the rotating cutter was advanced, it deviated from its intra-housing course and intruded into the vascular wall. Dislocation of the rotating blade was due to pressure from hard plaque tissue. After having carefully pulled back the complete catheter system, a severe spasm of the left main stem occurred, which was reversed by intracoronary nitroglycerine. The final angiography showed a left coronary artery without significant, residual stenosis. The case report underscores that DCA passes must be performed under continuous fluoroscopic control, especially for balloon-resistant lesions because of the unpredictability of DCA-imminent complication.

Atherectomy, Coronary↗
PubMed1995

Experimental directional atherectomy injury in arterial vessels: impact of trauma depth on cellular response.

This study investigates cellular alterations after directional atherectomy vessel injury (DI) in an experimental model in 50 pigs. Two hundred arteries were excised at eight different times (2 hours to 21 days) after DI and were examined by electron microscopy and immunohistochemistry. The extent of injury varied with the number of repetitive passes of the atherectomy catheter. According to the extent of injury the vessel segments with DI were assigned to three groups: intima injury (group 1), media injury (group 2), and adventitia injury (group 3). A myoproliferative response was found in relation to DI depth, increasing from group 1 (ratio tissue hyperplasia/media: 0.3 +/- 0.2; p < 0.001) to group 2 (ratio tissue hyperplasia/media: 1 +/- 0.5) and group 3. Intense neutrophil infiltration occurred in groups 2 and 3 (peak 12 hours after DI) and was followed by the early occurrence of synthetic smooth-muscle cells (SMC; > 50% of all SMC present). Volume fraction of desmin and actin was transiently reduced in injured media and myoproliferative tissue (7d: 9% vs > 90% normal media). SMC proliferation started in groups 2 and 3 at 48 hours and peaked at 7 days (+500% vs normal media, p < 0.001). After DI was done, vascular response started immediately and depended on injury depth. A transient myoproliferative response resulted, correlating with the extent of vessel trauma.

Actin Cytoskeleton↗
PubMed1995

A new catheter for prolonged local drug application.

BACKGROUND: Local drug delivery using a new 5F catheter with six small needles is described. The needles can be extended laterally into vascular tissue for drug deposition. METHODS: A fluorescent indicator (Photofrin) was injected with a new local drug delivery device into porcine carotid arteries. The vessels were explanted 15, 30, 60 min and 14 days after local drug delivery. Vascular segments were analyzed using semi-quantitative measurement of fluorescence (calculated in relation to a standard, 100% representing the maximum fluorescence achieved by systemic intravenous application of Photofrin). RESULTS: Maximum fluorescence was found in adventitia (15 min: 374%; 30 min: 388%; 60 min: 251%). In intimal tissue, the detected fluorescence was 107% after 15 min, 294% after 30 min, and 25% after 60 min. Media fluorescence was lower (15 min: 151%, 30 min: 102%, 60 min: 55%). No systemic drug content was measured. Fourteen days after local drug delivery, 15% of maximal fluorescence was still found in media but no adverse tissue hyperplasia was observed. CONCLUSIONS: These experiments demonstrate that high-dose perivascular local drug delivery is feasible and allows prolonged and selective application of drugs in a vessel segment without side effects.

Angioplasty, Balloon↗
PubMed1995

Enhanced migratory activity of vascular smooth muscle cells with high expression of platelet-derived growth factor A and B.

UNLABELLED: Proliferation and migration of vascular smooth muscle cells (SMCs) are major events in atherogenesis. It is known that platelet-derived growth factor (PDGF) stimulates both of these processes in a paracrine fashion, whereas autocrine stimulation has been shown only for proliferation. The aim of this study was to investigate the influence of PDGF expression in SMCs on migratory activity of these cells. SMCs were cultivated from the vascular tissue of 23 patients. Cellular motility was analyzed by a computer-assisted motion analysis system; 54 images per sample, obtained during an observation period of eighteen hours, were analyzed. PDGF-A and PDGF-B mRNA levels were determined by quantitative polymerase chain reaction (PCR) following reverse transcription. To quantitate mRNA content of SMCs, the authors coamplified cDNA copies of mRNA from cells and from a synthetic reference RNA in the same reaction vessel. Cells derived from atherosclerotic lesions produced a 1.6-fold increase of PDGF-A (P < 0.05) and a 5-fold increase of PDGF-B mRNA (P < 0.05) as compared with those from normal vessels. The migratory velocity (range 11.1-49.2 microns/hr) was independent of PDGF-A and PDGF-B mRNA expression. A significant correlation between levels of PDGF-A mRNA and PDGF-B mRNA and the degree of directional changes of SMCs on the covered track (klinokinesis) was found (P < 0.05). CONCLUSION: PDGF-A and PDGF-B mRNA expression is significantly correlated with positive klinokinesis without affecting migratory velocity. This finding reflects enhanced migratory activity of SMCs. Besides its known mitogenic effects, the authors present evidence that PDGF may act as an autocrine motogen* in SMCs.

Adolescent↗
PubMed1995

Migration behavior of human smooth muscle cells cultivated from restenotic and primary lesions.

Subintimal smooth muscle cell (SMC) migration is considered an essential determinant of arteriosclerosis and neointimal formation. In this study, a cell culture model was established to characterize migration activity of SMCs originating from restenotic and primary lesions. Plaques from symptomatic stenoses of 32 patients (19 men, 13 women; 4 carotid, 17 peripheral, 11 coronary lesions) were removed by percutaneous atherectomy or direct operative approach. Ten patients suffered from recurrent stenosis. Cell cultures were established by explantation of tissue samples. By indirect immunofluorescence microscopy, SMCs were shown to be the predominant cell type of all advanced lesions irrespective of their origin. The spontaneous cellular motility of SMCs was analyzed in vitro by means of a computer-assisted observation system. Cells of all groups exhibited random motility. SMC migratory velocity was found to be significantly (P < 0.001) greater in cells from restenotic lesions than in those from primary plaques. In conclusion, migration behavior of human SMCs originating from arteriosclerotic lesions may be quantified in vitro as a functional determinant characterizing restenotic versus primary lesions.

Aged↗
PubMed1995

Regulation of smooth muscle cell proliferation and its possible role in preventing restenosis post-angioplasty.

The introduction of balloon angioplasty in 1978 as an alternative treatment for vascular stenosis has created a new clinical problem: restenosis, the renarrowing that occurs after the procedure in certain patients. Restenosis is an important long-term complication, with an incidence of 30-50% within 6 months post-angioplasty. Three mechanisms contribute to vascular restenosis: recoil, thrombus formation and direct trauma. Growth factors which enhance the expression of other growth-regulating proteins, in particular "second messengers", proto-oncogenes and other cell cycle controlling proteins, are released by local thrombi and the injured arterial segment itself, resulting in an excessive inflammatory and myofibroproliferative response which culminates in restenosis. From investigations in animal models it is known that restenosis takes place in several phases: thrombosis, inflammation, cell proliferation and matrix formation. Various factors seem to interact in each particular phase, either as agonists or antagonists; hence the pathway that results in restenosis is complex. The introduction of directional percutaneous atherectomy has made it possible to examine human arterial tissue obtained in vivo, including restenosis material, from a sufficient number of patients in order to complement animal experiments. Not all of the mechanisms which lead to restenosis are known; nevertheless, after more than 15 years' experience of balloon angioplasty, there is an urgent need to develop therapeutic strategies based on currently available information. Selective elimination or alteration of proliferating cells, enhancement of natural growth inhibitors, blocking of signal transduction or inhibition of the gene expression for distinct growth-stimulating proteins all appear to be potentially promising.

Angioplasty, Balloon↗
PubMed1995

[Ultrastructural characteristics of cellular reaction to experimental catheter-induced lesions of arterial blood vessels].

UNLABELLED: After angioplasty, restenosis remains the major drawback of the procedure with an incidence of between 20-40%. It is a matter of concern whether the cellular alterations start immediately after directional atherectomy (DA) and if they are dependent on the depth of the lesion. METHOD: Cellular alterations immediately after DA were investigated using peripheral atherectomy in normal vessels of 30 pigs (A. femoralis, A. carotis communis). DA was used to remove material. The arteries were assigned to two groups according to the depth of vessel injury. (Group 1: lesions to the intima; Group 2: lesions to the media.) 68 arteries with 41 intimal and 27 media lacerations were excised 4 to 24 hours later and processed for transmission electron microscopy, histology and immunohistochemistry. RESULTS: Immediately after DA, thrombus formation at the site of the altered segment was found. A transient infiltration of polymorphonuclear leukocytes (PMN) occurred, especially if the media was lacerated, followed by the transformation of contractile smooth muscle cells (SMC) into the synthetic subtype. A marked myoproliferative response was found in Group 2 whereas only moderate tissue hyperplasia was seen in Group 1. CONCLUSION: The present data provides evidence that cellular alteration of the atherectomized vessel begins immediately after atherectomy. Subsequent to the initial temporary PMN infiltration, an activation of local SMC occurs at a very early stage. These effects and, in particular, a myoproliferative response were found lesions injured the internal elastic membrane, while only minor effects were seen when the lesion affected the intimal layer.

Animals↗
PubMed1995

[Drug and instrumental therapeutic approaches for prevention of restenosis].

In recent years, several of the shortcomings of coronary angioplasty have been successfully countered. With more effective measures of treating acute complications, better equipment and more experienced operators, there has been a subsequent expansion of the indications and the type of lesions suitable for angioplasty. In the long-term, however, the restenosis rate remains the limiting factor for the success of the procedure. To date, clinical studies using systemic therapy or alternative instrumental devices have not convincingly demonstrated a benefit in preventing restenosis. New devices have mostly been used to manage complications at angioplasty or to increase the type of lesions that can be tackled transluminally. This article will describe recent findings relating to the pathology of restenosis and then discuss a new therapeutic concept, local drug delivery to suppress restenosis. The aim of this method of drug application is to achieve a high local concentration of agents that inhibit restenosis, while avoiding systemic side-effects. Possible substances which could be utilized in this manner include conventional therapies such as platelet or calcium antagonists, or anti-thrombotic, anti-inflammatory or anti-proliferative treatments, and also novel agents such as gene therapy. The latter strategy might include inhibition of certain stimulatory factors that control restenosis, for example, through antisense oligonucleotides, or alternatively, augmentation of naturally occurring inhibitory factors, perhaps with expression vector plasmids and virus-mediated gene integration. The various ways in which these substances can be locally delivered to the arterial wall, together with results from initial experimental studies will be summarized. It is possible that eventually the combination of effective treatments with local drug delivery (LDD) may at last resolve the restenosis problem in patients.

Angioplasty, Balloon, Coronary↗
PubMed1994

Resection of guide catheter fragments during coronary atherectomy in aorto-ostial lesions: a note of caution.

Angioplasty of coronary aorto-ostial lesions is considered to be troublesome with decreased acute and long-term results and high complication rates. We report a patient with an ostial right coronary artery lesion which was treated after failed PTCA with directional atherectomy as a rescue intervention. After a favorable angiographic and clinical outcome, plastic material was found in the AtheroCath's housing due to resection of the tip of the guide catheter.

Angioplasty, Balloon, Coronary↗
PubMed1994

Adenosine: a sensitive marker of myocardial ischaemia in man.

OBJECTIVE: In the human heart, the significance of adenosine as an indicator of myocardial ischaemia is controversial. Since adenosine fulfils key functions in the regulation of cardiac metabolism, its sensitivity as a marker of tissue ischaemia was investigated in this study in relation to other metabolites such as hypoxanthine and lactate. METHODS: Cardiac metabolite production was studied in 18 patients with left coronary obstruction (> 90%) undergoing percutaneous transluminal coronary angioplasty (PTCA). Three balloon inflation procedures per patient were performed for 30, 60, and 90 s (+/- 5 s each) and coronary sinus adenosine, hypoxanthine, uric acid, and lactate were determined. RESULTS: Before PTCA, coronary sinus concentrations of adenosine and hypoxanthine were 176(SEM 34) and 723(73) nM, respectively, and the lactate concentration was 0.47(0.07) mM. Lactate was extracted by cardiac tissue during normoxia, and adenosine and hypoxanthine were in the physiological range of healthy volunteers. During reperfusion the concentrations of all myocardial metabolites were temporarily increased. In particular, adenosine was enhanced in close proportion to the duration of coronary occlusion. Moreover, coronary sinus adenosine, but not lactate, was significantly lowered during reperfusion when nifedipine (0.2 mg) was given by intracoronary injection before PTCA. CONCLUSIONS: With longer periods of coronary occlusion (> 30 s) the relative rank order of sensitivity indicating myocardial ischaemia was adenosine > lactate > hypoxanthine > uric acid. Coronary sinus concentrations of adenosine are quantitatively sufficient to be responsible for some of the changes in coronary blood flow occurring during reactive hyperaemia.

Adenosine↗