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Biomedical subjects

P Gonschior

Publications and source records attributed to P Gonschior.

At least 19 recordsLinked to original sources
PubMed2001

High-resolution MR angiography: results in diseased arteries.

The purpose of this study was to investigate the value of a respiratory-gated three-dimensional (3D) magnetic resonance angiographic technique (MRCA) in identifying coronary arteries in healthy volunteers and patients with proximal coronary artery stenoses and to compare the results of the navigator echo technique in the assessment of coronary artery stenosis with conventional coronary angiography. Twenty healthy volunteers and twenty patients with proximal coronary artery stenosis were examined at 1.5 Teslas with a cardiac-gated and retrospective respiratory-gated 3D gradient echo sequence. Visualization of the main coronary arteries was analyzed after curved MPR-reconstruction in three defined segments. For the assessment of image quality, a grading system including six scores was used to evaluate 400 vessel segments. Detection of coronary artery stenosis was compared with conventional coronary angiography by two blinded readers. In healthy volunteers, an image quality with a score of at least 3 (i.e., completely identified coronary arteries with major luminal irregularities) was found in 55% for the proximal segment, 47% for the middle segment and 20% for the distal coronary artery segment. Respective data for patients were 69% for the proximal segment, 47% for the middle segment and 20% for the distal segment. In contrast to other studies, we compared MRCA and conventional coronary angiography in the assessment of stenoses for all coronary vessels and for selected coronary vessels with high image quality. For the assessment of coronary artery stenoses (n = 53), sensitivity was 73% and specificity was 50% after evaluation of all patients by two blinded readers. A sensitivity of 79% and a specificity of 54% were found for evaluation of coronary vessels with an image quality score of at least 3. With the navigator echo MR technique, a complete 3D visualization of the main coronary arteries is possible in cases with variable image quality, but further experience and improvement of the prospective navigator echo sequence using shorter acquisition times is necessary for reliable assessment of coronary artery stenoses.

Coronary Angiography↗
PubMed1999

Navigator echo-based respiratory gating for three-dimensional MR coronary angiography: results from healthy volunteers and patients with proximal coronary artery stenoses.

OBJECTIVE: The purpose of our study was to investigate the value of respiratory-gated three-dimensional (3D) MR angiography in identifying coronary arteries in healthy volunteers and in patients with proximal coronary artery stenosis and to compare the results with those of conventional coronary angiography. SUBJECTS AND METHODS: Twenty healthy volunteers and 20 patients with coronary artery stenosis were examined on a 1.5-T scanner with a retrospectively respiratory-gated 3D gradient-echo sequence. Visualization of the main coronary arteries was analyzed after curved multiplanar reconstructions. A six-point grading system was used to evaluate 400 vessel segments. The assessment of stenosis was performed by two observers who were unaware of the results of conventional coronary angiography. RESULTS: The proximal, middle, and distal segments of the coronary arteries were completely identified with or without luminal irregularities in 55%, 47%, and 20%, respectively, of the healthy volunteers. For the 20 patients, results were 69%, 44%, and 20%, respectively. For the assessment of coronary artery stenoses (n = 53), sensitivity was 73% and specificity was 50% after evaluation of the MR angiograms of all patients. A sensitivity of 79% and a specificity of 54% were found for evaluation of the MR coronary angiograms, with an image quality score of at least 3 (i.e., artery segments completely identified with major luminal irregularities). CONCLUSION: With the navigator echo MR imaging technique, a complete 3D visualization of the main coronary arteries was possible in cases with high image quality. However, further experience with and improvement of the navigator echo technique we used is necessary for reliable assessment of coronary artery stenosis.

Adult↗
PubMed1999

Local drug delivery via transvascular injection.

BACKGROUND: In this experimental series we tested drug distribution and systemic leakage using local drug delivery with a new transvascular injection system. METHODS: Porcine femoral and carotid arteries (n = 56) underwent local drug application with a new 5 French (Fr) over-the-wire needle-injection catheter system (NIC) using three needles. A radioactive indicator [C14-Carvedilol, 2.0 milliliter (ml); 0.03 milligram (mg)] was injected in two carotid and two femoral vessels in parallel. Serial blood withdrawal was performed thereafter. After randomization to different explantation times, the vessels, perivascular tissue, liver and spleen were removed [0.5, 1, 1.5, 3 and 4 hours after injection, respectively]. Radioactivity was determined in a scintillation counter or with autoradiography. The indicator amount was calculated in relation to total drug amount (100%). RESULTS: Use of the NIC caused vessel texture alteration in non-diseased porcine vessels, seen as vessel wall penetration and perivascular edema. After single injection the maximum of the indicator was found in perivascular tissue 0.5 hours at the application site (carotid perivascular tissue: 7.48%; femoral perivascular tissue: 2.56%). Thereafter, radioactivity in the artery increased and perivascular content declined. The maximum in femoral arteries (1 hour; 1.96%) occurred earlier and was significantly lower compared to carotid arteries (2 hours; 7.75%). Four hours post-injection, 1.4% of total drug amount was detectable in the carotid arteries and 0.6% was detected in the femoral arteries. Systemic content was measured after C14-Carvedilol application with a maximum in serum of 28% (10 minutes), liver 30% (0.5 hour) and spleen 0.6% (0.5 hour). After 3 hours, still 5% of the indicator was still measureable in the serum and liver and less than 0.1% was measurable in the spleen. LDD with the NIC system is dependent on the vascular anatomy. The data indicate redistribution from perivascular to vascular space thus allowing a prolonged vascular and perivascular drug delivery. The amount deliverable is lower than expected due to substantial systemic drug contamination with this catheter.

Animals↗
PubMed1998

Local Drug Delivery for Restenosis and Thrombosis Ñ Progress?

Platelet activation, inflammation, recoil, tissue hyperplasia and remodeling are pivotal pathophysiologic factors in acute myocardial ischemia and restenosis development after angioplasty. Even after the rising use of stents, the tremendous amount of resulting tissue hyperplasia remains a therapeutic problem. 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; the drug was detectable for up to 21 days. In media, 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. (Supported by DFG Go 739/1-1).

Journal Article↗
PubMed1997

Endovascular catheter-delivered photodynamic therapy in an experimental response to injury model.

BACKGROUND: The effectiveness of local endovascular photodynamic therapy (PDT) in preventing tissue hyperplasia was evaluated in a vascular injury model. METHODS: Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries (n = 180). Animals (n = 72) were randomly allocated to unidirectional injury only (Group 1), injury followed by drug delivery of photosensitizer with a porous balloon (Group 2), or by local exposure to monochromatic light (Group 3). In Group 4, injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (PDT). Up to 21 days after treatment, all experimental vessels were excised, fixed and processed for histology, immunohistochemistry and transmission electron microscopy. RESULTS: After vascular injury an inflammatory and myoproliferative response was observed in Groups 1, 2 and 3 (mean tissue hyperplasia/media ratio 1.0 +/- 0.5 at 21 days; area tissue hyperplasia: 1.57 +/- 0.9 mm2). Proliferation in injured vascular segments (Group 1-3) reached a maximum at 7 days, with 6%. Only in Group 4, after injury followed by photodynamic therapy, was there no significant vascular response (mean tissue hyperplasia/media ratio 0.3 +/- 0.2: area tissue hyperplasia: 0.1 +/- 0.05 mm2 p < 0.001, proliferating cells 0.3%). CONCLUSION: Vascular response after unidirectional injury was suppressed only by endovascular photodynamic therapy.

Animals↗
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↗
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

Comparison of local intravascular drug-delivery catheter systems.

Systemic and local delivery of the photosensitive drug Photofrin polyporphyrin was investigated in normal porcine arteries (n = 192). A macroporous balloon and a novel needle injection catheter were used for local drug delivery and compared with systemic delivery. Fluorescence microscopy combined with digital image analysis was used to quantify the drug-related fluorescence. Systemic delivery showed a maximum in the intima at 4 hours. Application with the porous balloon revealed maximum indicator-related fluorescence intensity in the intima after 5 minutes; delivery with the needle injection catheter resulted in a several-fold enhanced maximum in adventitia after 30 minutes compared with the maximum achieved with either systemic injection or porous balloon application. After 21 days fluorescence was detectable in arteries treated with the new needle injection catheter. Local drug delivery is feasible with either system, but prolonged delivery was achieved only with the needle injection catheter.

Animals↗
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

[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

[Pathophysiology and pathobiochemistry of restenosis].

The high rate of restenosis after percutaneous transluminal angioplasty obviously depends on multiple factors. Predictors for the clinical outcome seem to be the selection of lesion morphology, the acute result and the biological vessel response in the first months after treatment. Thrombus formation and recoil have been considered to be pivotal events. Thus, anticoagulation and Ca-antagonists were routinely applied after treatment. Multiple studies with medical intervention have been performed, mostly with anticoagulants. However, no effective reduction of restenosis has been achieved so far. Analysis of autopsy tissue obtained after angioplasty indicated the importance of early vascular wall "response to injury" that might as a consequence lead to restenosis formation. This was confirmed by systematic experimental data. With introduction of directional atherectomy "biopsies" of primary and restenotic tissue were obtained. Thus, a subtile diagnostic spectrum including histological, immunohistochemical, electron microscopical, and molecular tissue analysis could be established. In vitro cultures of obtained tissue were performed routinely. They enable a characterization of proliferative and synthetic cellular features. Moreover, the effects of therapeutic measures can be quantified and used for pre-clinical screening. To date, the above described methods indicate as pivotal event the angioplasty induced transformation of contractile myocytes to a synthesizing type of myocytes. The transformation to synthetic active cells is not device dependent, but seems to be a major feature of restenosis. This process is mostly terminated in a period of 3-6 months. To accelerate this physiologic termination would be one interesting therapeutic option. Alternatively, special local drug delivery devices could be used to administer sufficient antiproliferative drugs at the site that needs to be treated.

Angioplasty, Balloon, Coronary↗