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Biomedical subjects

P Gonschior

Publications and source records attributed to P Gonschior.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Immunohistologic cell characterization of tissue of primary and re-stenoses].

Smooth muscle cells and macrophages are essential parts of arteriosclerotic lesions. This study should enable the analysis of different functional and morphological features of cells in primary and restenotic biopsies. Therefore detection of specific cell markers in human arteriosclerotic material derived from directional coronary atherectomy (DCA) of primary and restenotic lesions was used. Cryosections (2-4 microns) were stained immunohistologically (44 samples from 27 patients, 12 restenosis) with monoclonal antibodies. For further analysis antibodies against 5B5 (Prolylhydroxylase), alpha-actin, desmin and collagen I and IV were used. Endothelial structures (CD 31), T-cells and monocyte derived macrophages (CD 68, KP 1) were detected. In a second set-up alpha-actin and CD 68 were double-labelled. Semi-quantitative analysis in relation to total cell count was performed. The tissue removed consisted quantitatively of 78% intima- and 22% media-compartments and thrombus. 40% of the intimal area was comprised of low cellular compartments and in 57% high cellularity and foam-cells were found. In high cellular compartments 81% of the cells were positive for alpha-actin, only 13% of these cells were also positive for desmin. In intimal compartments in 58% of the cells macrophages were detected by CD-68 marker immunohistologically. 87% of these cells showed the expression of the 5B5 antigen (Prolylhydroxylase), in 90% monocytic antigenes were detected. Typical foam cells were not alpha-actin positive, whereas 40% of the CD 68 positive cells were alpha-actin positive. In myofibroblastic cells, positive staining with 5B5, collagen IV and extracellular matrix (collagen I) was present. Staining with antibodies against contractile filaments was diminished compared to the media compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1993

Analysis of atherectomy specimens.

Atherectomy specimens may be regarded as biopsy tissue excised from human vascular target lesions. Proceeding from contrary histologic findings that attribute focal hypercellularity to restenosis, and hypocellularity to chronic lesions, further analysis of atherectomy specimens was performed to study ultrastructural characteristics and functional aspects propagated by both lesion types. Transmission electron microscopy examination showed that intimal smooth muscle cells (SMCs) were the predominant cells in both primary and restenotic lesions. SMCs exhibited variable degrees of metabolic activation, typically higher in SMCs of restenotic lesions. This SMC phenotype was equally expressed when tissue samples were placed in a cell culture model. In an attempt to quantify SMC activity, proliferative as well as migratory activities of cultured cells were measured by growth curves and a computer-assisted motion analysis system, respectively. A 2- to 3-fold increase of both activity determinants was observed with SMCs cultivated from restenotic lesions compared with those from primary lesions, irrespective of their coronary or peripheral origin. Drug-induced interference of human SMC metabolic activation and antagonism to their proliferative and migratory activities may be helpful in evaluation of therapeutic concepts to prevent restenosis. The antitubulin colchicine was studied for its effect on the defined determinants. The data in vitro demonstrate that colchicine decreased proliferative and migratory activity of SMCs and caused disorganization of the cytoplasmic ultrastructure. In conclusion, electron microscopy and cell culture studies may help to shed more light on the structures and mechanisms underlying restenosis and plaque growth. Deliberate counteraction of any of the specific early events implicated in these complex pathobiologic processes may eventually become effective means to suppress restenosis and may thus result in a prophylactic as well as therapeutic treatment of the diseased vascular wall.

Animals↗
PubMed1993

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↗
PubMed1992

[The day-night rhythm in the 24-hour blood pressure profile. A possibility of distinguishing between primary and secondary hypertension?].

Automatic 24-hour blood pressure measurements were undertaken in 60 patients with primary systemic hypertension (24 women, 36 men; mean age 51 +/- 23 years) and 105 with secondary hypertension (36 women, 69 men; mean age 51 +/- 24 years). The aim of the study was to ascertain whether the absence of a day-night blood pressure rhythm is a reliable sign that the hypertension is secondary or whether it can also occur in primary hypertension. None of the patients was receiving any treatment. Day-night rhythm was abolished in 10 patients with primary hypertension (16%) and in 65 of those with secondary hypertension (62%). But an analysis of 11 case reports indicated that in an individual case there is no absolute rule. While absence of the day-night rhythm points to secondary hypertension, there are numerous exceptions.

Adult↗
PubMed1992

Efficacy of directional coronary atherectomy in cases unsuitable for percutaneous transluminal coronary angioplasty (PTCA) and after unsuccessful PTCA.

Directional coronary atherectomy (DCA) was used in 10 female and 50 male patients with an average age of 58 years. They were categorized into three different groups depending on the indications for atherectomy. Group 1 included all patients who had atherectomy as their primary intervention (n = 20) because they were assumed to be unsuitable for percutaneous transluminal coronary angioplasty (PTCA). Group 2 consisted of patients in whom DCA was used after failed balloon dilatation with unsuccessful but uneventful treatment (n = 17). Group 3 (n = 23) included patients in whom DCA was performed as a "rescue" or "bailout" procedure after unsuccessful PTCA resulting in critical ischemia (ECG changes, chest pain, hypotension, and shock). The target lesions were located in the left main artery in two, left anterior descending artery in 43, right coronary artery in 15, and aortocoronary venous bypass in five. The mean length of the lesions was 8 mm (2 to 25 mm). The overall success rate for 65 lesions was 92%. The mean stenosis was reduced from 87 +/- 12% to 19 +/- 17% in patients with primary success. Presently available follow-up angiograms (30) showed six restenoses. Major complications occurred in seven patients (myocardial infarction in two and coronary artery bypass graft surgery within 24 hours in five); there were no deaths. 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 unsuccessful PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1992

Rotational angioplasty and directional atherectomy to treat complex lesions of the right coronary artery.

A combination of interventional devices including the Rotablator and directional coronary atherectomy (DCA) was used to treat a 39-year-old patient with a complex lesion of the right coronary artery. The devices enabled the recanalization and reconstruction of the diseased vessel without laceration or dissection, leaving a smooth-edged segment. The histological analysis of the tissue obtained from DCA revealed no predictors of restenosis, like highly cellular material or media. Thus, combination of mechanical interventional devices allowed to treat a highly complex lesion without lacerating the vessel and leaving an excellent acute and long-term outcome.

Adult↗
PubMed1991

[Percutaneous peripheral atherectomy in arterial occlusive disease. Angiographic and clinical acute and long-term results].

130 arteriosclerotic lesions--10 in the iliac, 109 in the superficial femoral, 10 in the popliteal and 1 in the anterior tibial artery--were treated by percutaneous atherectomy in 80 patients (62 men and 18 women: mean age 65 +/- 10 years). 23 of the lesions were concentric, 65 eccentric stenoses, while 42 were fully occlusive. 32 patients were in stage IIb (after Fontaine), 24 in stage IIa and 12 each in stage III or IV. Most of the stenoses were not suitable for conventional balloon dilatation because of their primary morphology. A good early angiographic result (residual stenosis less than 50%) was achieved in 94% of lesions. Mean stenosis degree was reduced from 85 +/- 12% to 12 +/- 10% (occlusions from 100% to 9 +/- 9%). The Doppler index increased from 0.6 +/- 0.18 to 0.85 +/- 0.15 (P less than 0.01). Follow-up angiography after 6 months in 104 lesions demonstrated an average stenosis degree of 33 +/- 25% (occlusions 44 +/- 28%). 26 of the 104 re-studied lesions fulfilled the criterion for re-stenosis (greater than 50%): six concentric ones and five eccentric ones, as well as 15 occlusions. These findings indicate that peripheral atherectomy can be employed with good short and long-term results even in morphologically unfavourable, markedly eccentric or calcified lesions and occlusions.

Acute Disease↗
PubMed1991

[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↗
PubMed1991

[Uptake and distribution of hematoporphyrin derivatives (HPD) in arteriosclerotic and normal vessel segments].

Percutaneous treatment of vascular disease is limited by a relatively high long-term restenosis rate. Proliferation of smooth muscle cells may be one of the major reasons for restenosis. Therefore, due to its selective cytotoxic effect, photodynamic therapy (PDT) with HPD-injection and local laser light-application might be a promising therapeutic principle as prophylaxis of restenosis. Up to now, PDT has been used clinically in the treatment of superficial tumors. We studied its potential application as an antiproliferative modality for restenosis prophylaxis. Basic conditions for therapeutic use are: uptake of HPD in arteriosclerotic vessels; arteriosclerotic lesions show a higher photosensitivity than normal vessel after application of HPD. We investigated the uptake of HPD (Photofrin II) in normal (n = 15) and arteriosclerotic (primary lesions n = 52; restenosis n = 10) human vessel segments using quantitative fluorescence detection after incubation with 2.5 micrograms and 5 micrograms HPD/ml cell culture medium. HPD content, as reflected by fluorescence intensity, was measured after 15, 30, 60 min, and 24 h of incubation. Fluorescence intensity was concentration-dependent, with 80% of the maximal uptake reached at 1 h. A preferential uptake of HPD was measured in arteriosclerotic as compared to normal vessel segments (primary lesion: fluorescence-ratio of 3:1 at 1 h; restenosed lesion: fluorescence-ratio of 4:1 at 1 h). In addition, highly cellular plaque segments like restenosed material showed markedly increased fluorescence as compared to acellular matrix. Uptake of HPD was quickly (within 1 h) and preferentially detected in arteriosclerotic segments. A selective cytotoxic effect when combined with laser light may result and could be applied to restenosis prophylaxis.

Arteriosclerosis↗
PubMed1991

[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↗
PubMed1991

[Directional coronary atherectomy: acute results and angiography follow-up in 42 treated patients].

We used directional coronary atherectomy (DCA) as a therapeutic option for coronary lesions unsuitable for PTCA (eccentric, ostial, branching or restenotic) and as "rescue device" for failed PTCA. Forty-two patients were treated by DCA using the Simpson coronary atherectomy device, including four female and 38 male patients with an average age of 55.7 years. Atherectomy as primary intervention was performed in 16 patients (Group I), because morphology of their lesions was assumed to be unsuitable for PTCA. DCA was also used after failed balloon dilatation in eight patients with unsuccessful, but uneventful treatment (Group II). In 18 cases (Group III) DCA was performed as "rescue procedure" after failed PTCA and resulting critical ischemia (local dissection, signs and symptoms of ongoing ischemia, occlusion after PTCA). Target lesions were located in LM 1, LAD 33, RCA 9, CABG 3. Mean length of lesion was 8.1 mm (2-25 mm). The overall success rate for 46 lesions was 93%. Mean stenosis was reduced from 92% to 17% in cases with primary success. Presently, available follow-up angiography (24) showed six restenoses (defined as greater than 50% stenoses). Major complications occurred in seven cases (death: 0, MI: 2, CABG within 24 h: 5; 3 in Group III). "Rescue indication" (Group III) after failed balloon dilatation procedure showed a favorable primary result with a success rate of 78%; only three cases of this group needed CABG. Our results show that DCA is a safe and effective technique which can extend the indication for percutaneous procedures and gives a successful nonoperative option in cases of failed PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1989

Myocardial surface PO2--an indicator of myocardial tissue oxygenation?

The validity of myocardial surface tissue PO2 (PtO2) as a reliable indicator of transmural myocardial tissue oxygenation was studied in six anaesthetised, open chest pigs. Epicardial surface PtO2 was correlated with other variables of myocardial tissue oxygenation such as regional blood flow, coronary venous PO2, O2 saturation, PCO2 and regional myocardial lactate extraction. The study design was based on an experimental model in which the effects of a pacing induced tachycardia on tissue oxygenation of ischaemic and normally supplied myocardium were measured. Two platinum multiwire surface electrodes were placed on the epicardium, on the areas supplied by the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (CX). The LAD was constricted to reduce mean surface PtO2 in the LAD area to about 50% of its baseline value. This did not affect surface PtO2 in the CX area. The reduction of surface PtO2 in the LAD area was associated with decreases in coronary venous PO2 and O2 saturation and with increases in coronary venous lactate and PCO2. Subendocardial regional blood flow and the subendocardial to subepicardial flow ratio were significantly lower than in the CX area. Increasing the heart rate by pacing (+45 beats.min-1) led to an increased degree of ischaemia as shown by fall in surface PtO2 in the LAD area to values around zero kPa, by marked increase in coronary venous lactate and PCO2, by reduction in total (-10%) and subendocardial (-40%) LAD flow and by deterioration of the subendocardial to subepicardial flow ratio. The increased degree of ischaemia was not accompanied by an increase in O2 extraction. The marked decrease in surface PtO2 occurred in spite of a slight increase in the subepicardial regional blood flow (+10%); thus the increase in O2 delivery was not sufficient to meet the increase in O2 demand. Total flow was increased by 27% in the CX area without changes in the subendocardial to subepicardial flow ratio and in the surface PtO2 values. When pacing was stopped, surface values of PtO2 in the LAD area returned to prepacing values, as did lactate extraction and coronary venous PCO2. Clear and close relationships with surface PtO2 were found for regional lactate extraction, coronary venous PCO2 and the normalised subendocardial RBF. Poor or no correlations were found for the normalised subepicardial regional blood flow, the coronary venous O2 saturation and the absolute values of subendocardial and subepicardial regional blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Regional blood flow and tissue oxygen pressures of the collateral-dependent myocardium during isoflurane anesthesia in dogs.

The authors investigated the effects of isoflurane on blood flow and tissue oxygen pressures of a collateral-dependent myocardium. Seventeen dogs divided into two groups were studied 3-4 weeks after implantation of ameroid coronary artery constrictors to completely occlude the proximal part of the left anterior descending artery. Experiments were performed during anesthesia with an opiate that was infused intravenously throughout the experiments. In Group 1 (n = 9), measurements were obtained during control and during isoflurane- (1.6-2.2 vol%) induced hypotension (mean arterial pressure, 60 mmHg). In Group 2 (n = 8), the identical protocol was applied, but norepinephrine was infused to maintain normotension. Dipyridamole effects were studied in five animals of Group 2 after a second control period at least 1 h after discontinuation of isoflurane. Isoflurane-induced hypotension caused reductions of blood flow and surface tissue oxygen pressures in the collateral flow-dependent area. Vasodilation in the normal left ventricular areas was demonstrated by an unchanged blood flow despite a reduced oxygen consumption and by a significantly increased coronary sinus hemoglobin oxygen saturation. When arterial pressure was maintained at its control level by norepinephrine, tissue oxygen pressures remained constant and collateral as well as normal area flow increased significantly during isoflurane. Coronary vascular resistance was lower during administration of isoflurane and norepinephrine compared with that during isoflurane induced hypotension, suggesting a significant contribution of tissue oxygen demand in regulation of coronary vascular resistance. At comparable levels of arterial pressure and left ventricular oxygen consumption, normal zone blood flow was significantly higher during dipyridamole than during isoflurane and norepinephrine. Thus, isoflurane-induced hypotension decreased blood flow and tissue oxygen pressures of collateral flow-dependent myocardial areas. However, neither isoflurane nor dipyridamole caused such alterations when arterial pressure was normal.

Anesthesia, Intravenous↗
PubMedDate not supplied

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↗