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Biomedical subjects

F Gerheuser

Publications and source records attributed to F Gerheuser.

11 recordsLinked to original sources

[Spinal anaesthesia].

In spinal anaesthesia, surgical analgesia and in most cases motor block is achieved by injecting one or more drugs into the cerebrospinal fluid. As one of the earliest methods of anaesthesia it was introduced into clinical practice in the late nineteenth century. Although later on it was more or less replaced by "modern" general anaesthesia, it has regained popularity due to its benefits for certain patient populations. In spite of being a technically simple procedure, performing spinal anaesthesia requires a sound knowledge of applied physiology and pharmacology, especially in high-risk groups such as pregnant women or former preterm babies. For some patients even under anticoagulant therapy, spinal anaesthesia might be the best option, considering the individual risk of alternative methods.

Anesthesia, Spinal↗

[Desflurane in acute intermittent porphyria].

Despite the low incidence of the acute porphyrias, a profound knowledge of the disease is essential for anaesthesiologists, as a variety of perioperatively administered drugs are potential triggers of an acute attack. There is an ongoing discussion about the use of volatile anaesthetics in porphyrias, but halothane and isoflurane seem to be safe. There is no clinical data or case report about the use of desflurane in this specific patient group, but its fast and relatively unchanged elimination and the minimal induction of the cytochrome P 450 system seem to be favorable in this setting. We report the use of desflurane in a patient with acute intermittent porphyria, scheduled for hemihepatectomy. To minimize perioperative distress by pain or the need for postoperative mechanical ventilation, we chose a balanced anaesthesia technique with desflurane, sufentanil and atracurium in combination with a continuous epidural analgesia (bupivacain and fentanyl) for the postoperative period. Preoperatively the porphyrin precursors were analyzed in serum and urine and postoperatively the 24 h-urine was screened every 2 days until postoperative day 6 to monitor the porphyria activity. The preoperative data showed high concentrations of porphyrin precursor excretion, confirming the diagnosis of AIP. The postoperative data in the 24 h-urine were significantly lower than preoperative levels and reached normal levels at postoperative day 5. There were no clinical symptoms of a porphyric attack during the postoperative hospitalization. The patient was discharged on postoperative day 21 in excellent condition. We conclude that our perioperative management prevented an acute porphyric attack in this case. Desflurane might be a valuable alternative to other hypnotics in patients with AIP.

Aged↗

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↗

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↗

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↗

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↗

[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↗

Results of directional peripheral atherectomy with reference to histology, histochemistry, and ultrastructure.

One hundred patients with symptomatic peripheral vascular disease were treated with a directional atherectomy catheter; 153 lesions comprising 98 stenoses and 55 occlusions were located in the iliac (n = 22), superficial femoral (n = 114), popliteal (n = 16), and anterior tibial (n = 1) arteries. The majority of these patients were poor candidates for balloon angioplasty because of the complexity of lesions. There were 70 eccentric and 28 concentric lesions and 55 occlusions (mean length 4.2 +/- 2.9 cm). Acute success rate was 94% for both stenoses and occlusions. Four patients were treated in both lower extremities. The stenoses were reduced from 85 +/- 12% to 12 +/- 10% acutely (occlusions 100% to 9 +/- 9%). Six-month angiographic follow-ups were performed in 81% of treated patients, the others refusing angiography. Mean stenosis after six months was 33 +/- 25% (occlusions 44 +/- 28%). Restenosis (> 50%) was found in 20% of treated lesions: 26% in concentric lesions, 8% in eccentric lesions, and 32% in occluded vessels. Treatment of peripheral vascular disease with the atherectomy device is safe and effective therapy with good long-term results. These results were obtained in complex lesions with 55 occlusions. Atherectomy seems to be particularly beneficial in the treatment of eccentric and complex stenoses and is not limited by occlusion or calcification. Furthermore, insight into the pathogenesis of arteriosclerosis and the development of restenosis is enabled by analysis of removed plaque material.

Aged↗

[Current status of directional coronary atherectomy in interventional cardiology].

Directional coronary atherectomy (DCA) was used in 74 patients with an average age of 56 years. They were categorized into three different groups depending on the indications for atherectomy. Group I included all patients who had atherectomy as their primary intervention (n = 26), because they were assumed to be unsuitable for PTCA. Group II consisted of patients in whom DCA was used after failed balloon dilatation with unsuccessful but uneventful treatment (n = 20). Group III (n = 28) included cases where DCA was performed as a "rescue" or "bail-out" procedure after failed PTCA resulted in critical ischemia (ECG changes, chest pain, hypotension, and shock). The target lesions were located in LM 2, LAD 52, RCA 16, ACVB 4. The mean length of lesion was 8 mm (2-25 mm). The overall success rate was 94%. The mean stenosis was reduced from 90.6 +/- 10% to 17.2 +/- 14.8% in cases with primary success. The presently available follow-up angiography (n = 31) showed six restenoses. Major complications occurred in seven cases (death: 0, myocardial infarction: 2, CABG within 24 h: 5). Histological analysis revealed highly cellular areal as a major characteristics of a coronary lesion and also of restenotic tissue. Tissue of the lamina elastica was present in 44% and of media in 14%. Thrombus was found only rarely. Ultrastructure showed a significant amount of extracellular matrix in the primary coronary lesions and isolated smooth muscle cells without gap-junctions. RER, mitochondria were typical for the synthesizing type of smooth muscle cell. In restenotic tissue a focal high density of smooth muscle cells with increased synthesizing activity and gap-junctions was present. Endothelial cells (and macrophages) were found only rarely. Furthermore, altered smooth muscle cells from restenotic tissue showed a significantly increased migration and proliferation. Our results show that DCA is a safe and effective technique that can extend the use of percutaneous procedures and provide a promising, nonsurgical option in cases of failed PTCA. Histological analysis revealed a proliferative process as a characteristics of restenosis development.

Angioplasty, Balloon, Coronary↗

[Selective hematoporphyrin derivative (HMD) application in arterial vessels using a porous balloon catheter results in equivalent levels as compared to high-dose systemic administration].

The treatment of atherosclerotic vascular stenosis with percutaneous angioplasty is limited by a rate of restenosis of about 20-40%, in spite of new angioplasty devices. Histological and immune histological examinations of restenosed material obtained by coronary atherectomy indicate that cellular proliferation is an important determinant of restenosis. With the use of photodynamic therapy (PDT), it might be possible to selectively impair proliferating tissue by the application of the photosensitizer Photofrin II (a hematoporphyrin-derivative, HPD) followed by localized laser-light radiation. With the knowledge of the success of PDT in tumor therapy, the extension of the application of PDT in prophylaxis of restenosis should be examined. The technique used up to now works with the systemic application of the sensitizer. By applying HPD locally, however, one might be able to reduce the amount of the photosensitizer, but still achieve an equally cytotoxic effect. A recently developed catheter with a porous balloon enables local application of HPD. The following study describes the uptake and distribution of the hematoporphyrin-derivative Photofrin II within the walls of elastic and muscular type vessels after systemic and selective application. In 20 rabbits and seven pigs, Photofrin II was applied systemically (5 mg/kg i.v.) and locally (5 ml of 2.5 mg/ml). From each animal 12 vascular specimens (six arterial segments of either muscular and elastic type) were removed at a definite time within a defined period of 5 min to 24 h after application. To quantify the uptake of Photofrin II, we used fluorescence microscopy with digital image processing. After systemic application there was an increase of Photofrin II over a 4-h period. In contrast, a maximum concentration of Photofrin II was measured immediately after local application and found to be decreasing over a period of 4 h. The intima showed the highest uptake of HPD, both after local and systemic applications, as compared to uptake by the media and adventitia. The intimal uptake was significantly higher after local than after systemic application. Media and the adventitia showed, respectively, only one-half and one-fifth of the intima's intake. The rapid increase of the HPD concentration after local application would make PDT feasible in restenosis prophylaxis immediately after angioplasty without systemic side-effects of the photosensitizer.

Administration, Topical↗

Ultrastructural characteristics of cellular reaction after experimentally induced lesions in the arterial vessel.

UNLABELLED: Restenosis after angioplasty occurs with an incidence of 20-50% and remains a major drawback. Certain randomized studies suggest that a bigger post-angioplasty lumen predicts a better long-term outcome. Conversely other studies showed a better outcome with limited injury. The present study aimed to investigate the depth of the lesion and relate this to cellular alterations after graded vascular injury. METHOD: Vessel segments of 30 pigs underwent injury using a directional atherectomy catheter. Vessels were assigned according to the extent of injury to Group 1 (intima lesion) or Group 2 (media injury). 2 hours to 7 days after injury, 68 arteries showing 41 intimal and 27 media lacerations were excised and processed for histology and transmission electron microscopy. RESULTS: Immediately after injury, thrombus formation was found at the site of the altered segment. A marked, transient infiltration of polymorphonuclear leukocytes (PMN) occurred only if the media was lacerated, starting within the first hours and increasing up until the 12 hours time point. The cellular infiltration was followed by a transformation of contractile myocytes to a synthetic subtype. The ratio of myofilaments to organelles decreased. A pronounced myoproliferative response was found in Group 2 after 7 days (p < 0.01), whereas only moderate tissue hyperplasia was seen in Group 1. CONCLUSION: The data presented provide evidence that the cellular alteration of injured vessels begins immediately. Subsequent to an initial temporary PMN infiltration, an activation of local myocytes occurs at a very early stage. In particular, a myoproliferative response was found only after deep injury with rupture of the internal elastic lamina.

Animals↗