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M D Menger

Publications and source records attributed to M D Menger.

At least 127 records · Page 7Linked to original sources
PubMed1998

In vivo analysis of microvascular injury after myocardial cryothermia.

We studied microvascular injury after myocardial cryothermia in rats using intravital fluorescence microscopic techniques. Cryolesions were induced to the right ventricle by freezing with -160 degrees C (probe diameter: 5 mm) for a total of 5 min. Fluorescence microscopy was performed at 15, 30, 60, 90, and 120 min as well as at 3 and 7 days after cryothermia. Analysis of the epicardial microvasculature 15 min after cryothermia revealed an area of 24.6 +/- 3.8 mm2 of nonperfused tissue, which was reduced to 5.3 +/- 1.5 mm2 (P < 0.05) after the initial 2-h observation period. Vital microscopic images of reperfused tissue characteristically demonstrated extravasation of the macromolecular fluorescent tracer FITC-dextran (21.7 +/- 3.4 mm2), suggesting substantial loss of endothelial integrity. In vivo propidium iodide staining confirmed membrane damage of microvascular endothelial cells. Three days after cryoinjury the area of nonperfused tissue was reduced further to 1.1 +/- 0.4 mm2 in the center of the lesion, while the area of perfused tissue with disruption of endothelial integrity was found significantly increased to 47.4 +/- 5.9 mm2 (P < 0.05) toward the periphery. Analysis at 7 days revealed endothelial repair at the periphery of the cryolesion, but now a central necrotic area was found demarcated (nonperfused), presenting with a size (26.0 +/- 3.5 mm2) similar to that shown during the very early (15 min) reperfusion period. Our study demonstrates recovery of microvascular perfusion during the first hours and days after myocardial cryothermia. This is, however, associated with endothelial injury, i.e., damage of plasma membrane and loss of barrier function. Infarction with capillary perfusion failure is evident at 7 days with a size which strikingly corresponds to the sizeof nonperfused tissue observed immediately after cryointervention.

Animals↗
PubMed1998

A novel approach for comparative study of periosteum, muscle, subcutis, and skin microcirculation by intravital fluorescence microscopy.

Herein, we report a new model, which allows comparative study of the microcirculation of different peripheral tissues, i.e., periosteum, skeletal muscle, subcutis, and skin. Using dextran-insensitive Wistar rats gracilis and semitendinosus muscles of the left hindlimb were prepared in association with their appertaining tibial fragments, subcutis, and skin. Blood supply was guaranteed by the femoral artery via the saphenous vessels. High-resolution intravital epi-illumination microscopy of the two muscles displayed the typical microvascular architecture with the capillaries running in parallel to each other (capillary density (CD) 128.4 +/- 4.5 cm-1). In subcutis and skin, capillaries were found arranged as interconnecting mesh-like networks with a density, which was significantly higher (P < 0.05) in subcutis (191.0 +/- 5.5 cm-1) compared with skin (108.9 +/- 3.3 cm-1). Analysis of periosteal tissue revealed two distinct types of arrangements of microvascular architecture. Adjacent to the major feeding and draining vessels of the periosteum, capillaries were organized in densely meshed shunt-like networks, revealing the highest capillary density (242.7 +/- 13.2 cm-1; P < 0.05) of all tissues studied. Periosteal capillaries distant from the major feeding and draining vessels were arranged in parallel to the longitudinal axis of the tibial bone and presented with a density similar to that of the skeletal muscle (128. 6 +/- 9.4 cm-1). Topical application of acetylcholine for analysis of physiological reactivity of the microvasculature showed dose-dependent arteriolar dilation. Moreover, a 3-min upstream femoral artery occlusion demonstrated an appropriate hyperemic response in all tissues studied, indicating intact myogenic control. A prolonged period of ischemia (120 min) followed by reperfusion (60 min) caused massive (P < 0.05) leukocyte-endothelial cell interaction in postcapillary venules, similarly as reported in other microvascular tissue preparations. We propose that the model presented provides a good approach to all peripheral tissues for both the analysis of the physiology of tissue-confined microvascular control and the development of novel therapeutic strategies to counteract manifestation of nutritional dysfunction and inflammatory response in disease.

Acetylcholine↗
PubMed1998

[The effect of gamma-hydroxybutyrate (GHB) on proinflammatory cytokine gene expression in coronary surgical procedures].

OBJECTIVE: To determine the influence of gamma-hydroxy-butyrate (GHB) on spontaneous and lipopolysaccharide (LPS)-stimulated release of tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interleukin-10 (IL-10) in whole blood from patients undergoing coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC). In addition, the pharmacological modulation on lipopolysaccharide (LPS)-stimulated cytokine release by GHB (GHB-Na and GHB-ethanolamide) was characterized in a separate in vitro-assay. METHODS: In a prospective, randomized, double-blinded study, 12 patients undergoing elective CABG were assigned to receive either saline (control) or GHB-Na (25 mg/kg as loading dose followed by 25 mg/kg/h) intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min after ECC and (C) 24 h after ECC. Plasma levels (spontaneous release) as well as LPS-stimulated cytokine secretion were measured in a whole blood culture system ex vivo and correlated with mRNA-expression in peripheral blood mononuclear cells (PBMC). In addition, the dose-response characteristics of modulation of the cytokine response by GHB was studied in vitro in the same assay. RESULTS: Plasma IL-6 and IL-10 levels were significantly elevated after CABG, while TNF and IL-1 beta were detectable only occasionally in both groups. Expression of all cytokines studied was significantly reduced upon ex vivo LPS-stimulation at time point B. Despite maintained expression of TNF and IL-1 beta mRNA-transcripts upon ex vivo LPS-stimulation in patients treated with GHB, release of the cytokines in the supernatant was decreased to a similar degree as in the control group. Cytokine response upon LPS-stimulation was restored 24 h after CABG for the group mean, however, with substantial individual heterogeneity. In vitro, pharmacological doses of GHB-Na (2 mg/ml) attenuated LPS-induced IL-1 beta release. However, application of the GHB-receptor antagonist NCS-382 caused a nearly complete cessation of IL-1 beta release in vitro (to 2.5% of control). GHB-ethanolamide (LK 544) did not influence the LPS-stimulated release of the cytokines studied. CONCLUSION: The results suggest a biphasic response of stimulated PBMC cytokine gene expression during CABG with an initial tolerance to LPS-stimulation shortly after termination of ECC. However, whether or not PBMC express functional GHB receptors remains unclear in light of contradictory effects of the different ligands. In spite of the ex vivo and in vitro results, application of GHB-Na in doses which are primarily based on its use as an anesthetic agent do not seem to modulate the release of the cytokines studied.

Adult↗
PubMed1998

Cold preservation of the small intestine with the new Celsior-solution. First experimental results.

The aim of the present study was to evaluate the potential of Celsior, a recently developed cardioplegic and heart storage solution, to protect the small bowel during ischemic storage. Small bowel segments were isolated from rats, flushed with either UW or Celsior solution, and cold-stored for 18 h at 4 degrees C in the respective solution. After ischemic storage, some preparations were freeze-clamped for analysis of tissue metabolites while other preparations were tested for structural and functional integrity by isolated perfusion in vitro using a previously validated model. After 18 h of ischemic storage no significant differences were seen between Celsior and UW with regard to the development of edema, energy charge, or creatine phosphate, but lactate accumulation was significantly reduced in the Celsior group, although glucose catabolism was not inhibited. Histological evaluation of the cold-stored organs showed no differences with regard to structural integrity between the two groups. Total vascular resistance upon reperfusion was significantly lower in the Celsior group (666 +/- 126 vs 827 +/- 88 MPa s m-3*), as was the intestinal release of LDH (9.7 +/- 4.4 vs 18.2 +/- 4.6 U/l*). Carbohydrate absorption from the intestinal lumen amounted to venous effluent concentrations of 0.58 +/- 0.24 vs 0.18 +/- 0.15 mg% * of galactose in the Celsior and UW groups, respectively. Within the limits of this in vitro pilot study, Celsior provided better postischemic recovery of the small bowel than UW in terms of vascular perfusion characteristics, enzyme release, and carbohydrate absorption and may, thus, be considered a suitable alternative for intestinal organ preservation.

Adenosine↗
PubMed1998

The use of intravital microscopy in surgical research. 26-years of experience analyzed by studies presented at the Surgical Forum of the Annual Congress of the German Society of Surgery.

Recent developments in intravital microscopy make this technique an attractive approach to studying microvascular, cellular, and molecular mechanisms of distinct surgical diseases. We investigated the value of this technique in surgical research laboratories by analyzing the studies presented during the past 26 years (1972-1997) at the Surgical Forum of the Annual Congress of the German Society of Surgery. From a total of 2279 papers 188 contributions (8.3%) presented data which derived from the analysis of the microcirculation using techniques, such as H2 and 133Xe clearance, autoradiography, thermodiffusion, laser Doppler fluxmetry, laser speckle, radioactive and fluorescent microspheres, polarographic oximetry, and intravital microscopy. There were 72 presentations (3.2% of all contributions) reporting the use of intravital microscopy, thus reflecting 38.3% of all microcirculatory analyses. Although these numbers may be considered quite small, analysis over time revealed a significant (P<0.05) increase in the number of microcirculatory studies (11.4%) and in particular of those using intravital microscopy (6.3%) in the 1990s when compared to the 1970s (5.3%; 0.1%) and 80th (7.1 %; 1.3%). In 1997, 27 of 165 contributions (16.4%) included microcirculatory analyses, and 18 of the 165 contributions (10.9%) reported results analyzed by intravital microscopy. Thus our analysis reflects an increasing interest of surgical researchers to study in vivo the microcirculation, and by doing so to use intravital microscopy for the elucidation of mechanisms of surgical disease.

Germany↗
PubMed1998

Cell surface and nuclear changes during TNF-alpha-induced apoptosis in WEHI 164 murine fibrosarcoma cells. A correlative light, scanning, and transmission electron microscopical study.

Tumour necrosis factor (TNF)-alpha-induced apoptosis is associated with several nuclear and cell surface alterations, in particular with the condensation of chromatin and the fragmentation of the cell nucleus, formation of blebs on the cell surface and breakdown of the plasma membrane. However, there is little information about the relationship between the cell surface alterations and the nuclear changes during apoptosis. To study this, cultured WEHI cells were exposed to TNF-alpha over different time periods. The cytological changes were studied using a correlative approach, which allowed observation of the same cell consecutively under light, scanning and transmission electron microscopy. The earliest sign of cell alteration was a reduction of the number of microvilli after 15 min of TNF-alpha exposure. This reaction was reversible (reappearance of microvilli) and took place during the first hour, in which neither nuclear alterations nor plasma membrane breakdown were observed. The changes in the nucleus began with condensation of chromatin after approximately 1 h of TNF-alpha-exposure. After 4-5 h the microvilli disappeared again, particularly in areas where the formation of blebs (blebbing) was observed. Strikingly, cell surface alterations (bleb formation) were detected only in those cells that presented with condensed chromatin, and not in cells with a normal chromatin pattern, proving at least a close correlation between nuclear and cell surface changes during the process of apoptosis.

Animals↗
PubMed1998

Differential effect of cyclooxygenase metabolites on proinflammatory cytokine release by Kupffer cells after liver ischemia and reperfusion.

BACKGROUND: Liver ischemia and reperfusion (I/R) induce Kupffer cell (KC) activation with increased release of proinflammatory cytokines. Prostaglandins are potent counterregulatory mediators to control the production of cytokines by macrophages. METHODS: To study the role of cyclooxygenase metabolites for the release of proinflammatory cytokines by KC in liver I/R, Sprague-Dawley rats were subjected to 20-minute global hepatic ischemia and 60 minutes of reperfusion. Sham-operated animals were used as controls. Kinetics of spontaneous and lipopolysaccharide (LPS)-induced release of proinflammatory cytokines and prostaglandin E2 (PGE2) by KC were assessed both in the presence and absence of the cyclooxygenase inhibitor ibuprofen. RESULTS: Early after liver I/R (4, 16 hours) the spontaneous secretion of TNF-alpha (+1,058%), IL-1alpha (+152%), and IL-6 (+161%) by KC was increased (P <0.05), while PGE2 release in the I/R group was reduced by 51% (P <0.05) in comparison with the sham-operated group. Increased release of PGE2 in the later period (32 hours) after I/R was associated with decreased TNF-alpha release by KC. Inhibition of PGE2 production by ibuprofen induced a prolonged and enhanced production of TNF-alpha, while the release of IL-1alpha and IL-6 was not affected. CONCLUSIONS: Liver I/R leads to a temporary suppression of PGE2 release by KC, while the release of TNF-alpha is increased. Thus, during early reperfusion, excessive secretion of TNF-alpha by KC may be the result of the absent negative feedback control of cyclooxygenase metabolites.

Animals↗
PubMed1998

In vivo analysis of antithrombotic effectiveness of recombinant hirudin on microvascular thrombus formation and recanalization.

PURPOSE: This study was undertaken to evaluate in vivo the effect of recombinant hirudin (r-hirudin [HBW 023]), a potent thrombin inhibitor, on the process of microvascular thrombus formation and recanalization. METHODS: Thrombosis was induced photochemically in distinct arterioles (n = 25) and venules (n = 30) of the ear of 16 hairless hr/hr mice (8 to 10 weeks old, 25 to 30 g of body weight). r-Hirudin (1 mg/kg of body weight) was administered intravenously directly before thrombus induction; saline-treated animals served as controls. Thrombus formation (i.e., first platelet deposition at the endothelial lining [FPD]; inner luminal diameter reduction to 50% [D/2]; complete vessel occlusion [CVO]), vessel recanalization, microcirculatory parameters, and leukocyte-endothelial cell interaction were analyzed by means of intravital fluorescence microscopy. RESULTS: Hirudin significantly delayed the process of thrombus formation compared with saline-treated controls in both arterioles (FPD: 381 +/- 80 vs 137 +/- 25 seconds, P < 0.05; D/2: 627 +/- 49 vs 501 +/- 71 seconds; CVO: 925 +/- 78 vs 854 +/- 60 seconds) and venules (FPD: 173 +/- 11 vs 59 +/- 4 seconds; D/2: 342 +/- 54 vs 228 +/- 27 seconds; CVO: 541 +/- 85 vs 344 +/- 43 seconds; P < 0.05). In addition, r-hirudin-treated animals showed an increased rate of vessel recanalization at 24 hours after thrombus induction (arterioles: 54% [7 of 13] vs 0% [0 of 12], P < 0.05; venules: 77% [10 of 13] vs 53% [9 of 17]), whereas microcirculatory parameters and leukocyte-endothelial cell interaction were not affected. CONCLUSION: Our data indicate that r-hirudin not only counteracts the process of thrombus formation but also promotes vessel recanalization, thus supporting its use in clinical microvascular surgery.

Animals↗
PubMed1998

In vivo assessment of the influence of cold preservation time on microvascular reperfusion injury after experimental small bowel transplantation.

BACKGROUND: This study describes the impact of prolonged cold storage on microvascular reperfusion injury of transplanted rat small bowel isografts. METHODS: In vivo fluorescence microscopy was used to assess intestinal microcirculation after 6, 12, 18 and 24 h of cold (4 degrees C) ischaemia in University of Wisconsin solution and 20-90 min of reperfusion. Sham-operated animals served as controls. RESULTS: Whereas 6 and 12 h of ischaemia did not affect functional capillary density of the intestinal graft mucosa, villous perfusion was significantly impaired after 18 and 24 h of cold preservation. Similarly, microvascular perfusion of circular and longitudinal muscle was not affected after 6 h, but deteriorated following prolonged cold ischaemia. Leucocyte-endothelial cell interaction in submucosal venules was significantly enhanced after 6 h of ischaemia with peak values after 12 and 18 h. A progressive reduction of lymphatic capillary drainage indicated an ischaemia time-related deterioration in graft function. CONCLUSION: The results provide evidence that leucocyte-endothelial cell interaction in submucosal venules of the transplanted intestine is a primary step in the manifestation of reperfusion injury following short periods of cold ischaemia.

Animals↗
PubMed1998

Characterization of angiogenesis and microcirculation of high-grade glioma: an intravital multifluorescence microscopic approach in the athymic nude mouse.

The current study follows angiogenesis and microcirculatory changes associated with malignant glioma growth by means of an intravital fluorescence microscopic approach, which allows for the direct and continuous visualization of the glioma microvasculature and its quantitative analysis. Fluorescently labeled C6 rat glioma cells (5 x 10(5)) were implanted into dorsal skinfold chamber preparations of athymic nude mice. Glioma growth, vascularization, microhemodynamics, vascular permeability, and leukocyte-endothelial cell interactions were simultaneously followed over a 22-day observation period using intravital epiillumination microscopy and a multifluorescent labeling technique. Analysis of the process of glioma vascularization revealed three stages with distinct microvascular characteristics: avascular stage (days 0 to 6), lag of glioma growth but initial glioma-induced angiogenesis within the host tissue in peritumoral areas; early vascular stage (days 6 to 14), glioma cell proliferation associated with a spatially homogeneous development of a glioma microvasculature; and late vascular stage (days 14 to 22), exponential tumor growth and expansion (> 400 mm3) with high vascular densities in the peritumoral region and reduced vascularization (microvascular perfusion) in the glioma center. Within the center, the functional vessel length per area correlated inversely with glioma size (P < 0.01). In the peritumoral region, functional vessel length per area was independent of glioma size, indicating persistent, high angiogenic activity throughout the observation period. Thus, the microvasculature of mature gliomas revealed a microvascular zonal division with a progressive reduction of the functional vessel length per area within the tumor center. The perfusion failure of individual microvessels within the glioma center was partly compensated by an increase of diameters (P < 0.05), and thus by an increase of blood flow in these functional microvessels (P < 0.05) over time. Histologic analysis demonstrated both expanding and infiltrating growth patterns, as well as focal necroses on day 22. These are the first data from repeated in vivo analysis of glioma growth, vascularization, and microcirculation.

Animals↗
PubMed1998

Effects of local cooling on microvascular hemodynamics and leukocyte adhesion in the striated muscle of hamsters.

OBJECTIVES: Cellular metabolism is dependent on the local temperature in tissues. Induced hypothermia has been shown to be protective in a number of conditions, especially traumatic, ischemic, burn, and neurological injury. However, the protective mechanisms of cold therapy remain controversial and the hemodynamic changes in the microcirculation of striated muscles in response to hypothermia have not been studied in detail previously. METHODS: In this study, we investigated the microvascular response of local cooling and rewarming in the striated muscle of hamsters by use of the dorsal skinfold preparation and in vivo fluorescence microscopy. RESULTS: We found that reduction of the surface temperature to 8 degrees C for 30 minutes caused arteriolar vasoconstriction with a decrease in diameters by 43+/-7% while the venular and capillary diameters remained unchanged. The cooling procedure also markedly reduced the functional capillary density and the blood flow velocity and diameters in all vessel types, i.e., arterioles, venules, and capillaries. Moreover, the percentage of capillaries with no flow increased from 0.4+/-0.5% to 44+/-14% after 10 minutes of cold therapy. However, these hemodynamic changes induced by local hypothermia were completely reversed to the precooling values after termination of cooling and 30 min of rewarming. Strikingly, we found no increase in the number of adherent leukocytes and vascular permeability after the cooling and rewarming period, while, in contrast, additional experiments with warm ischemia (30 minutes) and reperfusion (30 minutes), i.e., reduced microvascular perfusion and reperfusion at normothermia, caused a sustained decrease in local perfusion and a nine-fold increase in venular leukocyte adhesion. CONCLUSIONS: Taken together, our functional data demonstrate that hypothermia markedly reduces microvascular perfusion, which is completely restored upon rewarming. The reduced microvascular perfusion during hypothermia did not provoke an inflammatory response, whereas leukocyte recruitment was prominent after reduced perfusion at normothermia, indicating that transient hypothermia has no adverse effects on microvascular parameters in the striated muscle in vivo.

Animals↗
PubMed1998

Reduction of skin flap necrosis by transdermal application of buflomedil bound to liposomes.

The influence of the vasoactive drug buflomedil hydrochloride bound to liposomes (2 mg/ml) was investigated in an arterial pattern skin flap model using the ear of hairless mice. For flap creation, the ear is cut at four-fifths of its base, which leaves the anterior artery as the only feeding vessel of the flap. Liposomes were locally applied daily for 30 minutes up to 5 days after flap creation. Microvascular perfusion in the proximal, central, and distal parts of the flap was measured by laser Doppler flowmetry. The border between perfused and nonperfused tissue was visualized by intravital fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled dextran (Mr 150,000) for contrast enhancement of microvessels. The area of nonperfused tissue was assessed by digital planimetry. Five days after flap creation the nonperfused area amounted to 23.8 +/- 3.1 percent of total flap surface in treated ears compared with 46.1 +/- 5.6 percent in untreated ears (p < 0.05) of the contralateral side. Additional preoperative treatment for 5 days did not further reduce the area of nonperfused tissue (treated ears, 23.0 +/- 1.3 percent; control ears, 44.6 +/- 5.1 percent). Microvascular perfusion was higher in the postoperatively treated ears in all parts of the flap from day 1 after flap creation until termination of the experiment. Five days after flap creation, perfusion as measured by laser Doppler flowmetry was reduced to 46.0 +/- 10.8 percent in the distal part in control ears compared with 91.9 +/- 8.3 percent (p < 0.05) in treated animals. Additional preoperative treatment for 5 days did not result in further improvement. It is concluded that local application of the vasoactive drug buflomedil docked to liposomes could be of therapeutic use in the treatment of ischemic tissue, including skin flaps.

Animals↗
PubMed1998

Proinflammatory cytokine gene expression in whole blood from patients undergoing coronary artery bypass surgery and its modulation by pentoxifylline.

The influence of coronary artery bypass grafting (CABG) on spontaneous and lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 as well as its modulation by pentoxifylline (PTF) were studied in a prospective, randomized, double-blinded study. 12 patients undergoing elective CABG were randomly assigned to receive either saline or PTF (1 mg/kg as a loading dose followed by 1 mg/kg/h) intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min after CABG, and (C) 24 h after CABG. Cytokine plasma levels as well as LPS-stimulated cytokine secretion were measured in a whole blood culture system ex vivo and correlated with mRNA expression in peripheral blood mononuclear cells. In addition, the dose-response characteristics of modulation of the cytokine response by PTF were studied in cultured whole blood in vitro. Plasma IL-6 and IL-10-levels were significantly elevated after CABG, whereas neither TNF-alpha nor IL-1beta were detectable. In contrast to the spontaneous release of IL-6 and IL-10, the expression of all cytokines studied was significantly reduced upon ex vivo LPS stimulation early after CABG. Proinflammatory cytokine response upon LPS stimulation was restored 24 h after CABG for the group mean, however, with substantial interindividual heterogeneity. Therapeutic doses of PTF in vitro attenuated LPS-induced TNF-alpha (-50.5%) and most notably IL-10 (-83.9%) release, whereas IL-1beta was even increased (+45.7%). However, application of PTF during CABG neither inhibited the spontaneous production of IL-10 nor modulated cytokine production ex vivo. These results suggest a biphasic response of stimulated peripheral blood mononuclear cell cytokine gene expression during CABG with an initial tolerance to LPS stimulation. The application of PTF during CABG in doses that are primarily based on its use in occlusive arterial disease do not seem to modulate the release of the cytokines studied.

Adult↗
PubMed1998

Striated muscle microvascular response to zymosan-induced generalized inflammation in awake hamsters.

The effect of zymosan-induced generalized inflammation on the microcirculation of distant striated skin muscle was studied for a 12 day period in awake Syrian golden hamsters (n = 18) using the dorsal skinfold chamber model and intravital fluorescence microscopy. Intraperitoneal zymosan exposure (125 mg/100 g body weight) induced significant nutritive perfusion failure in the distant striated muscle tissue at Day 1 without complete recovery over the 12 day observation period, as indicated by the marked reduction of functional capillary density when compared with both baseline values and values of sham-treated control animals. Moreover, intraperitoneal zymosan exposure induced endothelial disintegration, as demonstrated by the continuous increase of macromolecular leakage throughout the 12 days of observation. Strikingly, zymosan did not induce significant leukocyte adherence to the endothelial lining of postcapillary and collecting venules of the striated muscle tissue. Thus, we conclude that in this model of generalized inflammation nutritive perfusion failure and loss of endothelial integrity in distant striated muscle is not mediated by activated leukocytes, but must rather be attributed to direct toxic effects of mediators, elicited by the local (intraperitoneal) zymosan challenge and systemically released.

Animals↗
PubMed1998

Experimental intracoronary stenting: comprehensive experience in a porcine model.

Appropriate animal models for intracoronary stenting are most important for improving understanding of the pathophysiology of acute occlusion and long-term re-stenosis, which currently limits the safety and efficacy of percutaneous transluminal coronary angioplasty in humans. Since the anatomy and physiology of swine coronary arteries closely resemble those of humans, the procine model should be ideal for testing of stents. This is a comprehensive report on an experimental set-up in pigs, communicating in detail the necessary techniques as well as some modifications facilitating safe intracoronary stent placement and successful follow-up studies for weeks or months. Stent procedure is performed in mechanically ventilated and haemodynamically monitored animals under balanced anaesthesia. Intracoronary application of flow wires allows the assessment of local flow conditions, flow properties and coronary flow reserve. Real-time intravascular ultrasonography (IVUS) provides detailed information on coronary morphology and enables the appropriate sizing of the coronary lumen. From our own experience, we like to propose that the use of the porcine model has the potential to gain new insights into the pathophysiology of intracoronary stent placement-associated complications and allows for the study of modifications in techniques and materials, and the development of novel pharmacological therapeutic strategies.

Angioplasty, Balloon, Coronary↗
PubMed1998

Vascularization of purified pancreatic islet-like cell aggregates (pseudoislets) after syngeneic transplantation.

To clarify whether avascular purified endocrine cell aggregates derived from islets of Langerhans (pseudoislets) revascularize similarly to what is known for intact pancreatic islet grafts, we studied the process of angiogenesis and revascularization of syngeneically transplanted pseudoislets using intravital fluorescence microscopy. Pseudoislets were composed of pure beta-cells (B) or non-beta-cells (NB), as well as of mixed beta- and non-beta-cells (B/NB; 70/30%) or nonsorted-cells (NC), and were transplanted into the dorsal skinfold of Syrian golden hamsters. Intact islet grafts served as controls. At day 6 after transplantation, microvascularization of all types of pseudoislets was found to be less than in controls, as indicated by a reduced number of transplants that contained newly formed microvessels (take-rate: B, 38.8; NB, 38.7; B/NB, 43.8; and NC, 40.3% vs. intact islet grafts, 71.9%; P < 0.01). Moreover, those pseudoislets that had developed a microvascular network revealed a significantly lower functional capillary density (145.8+/-49.5 to 241.0+/-47.5 cm(-1) vs. intact islet grafts: 459.8+/-65.6 cm(-1); P < 0.05). After 20 days, the take-rate of pseudoislets was still lower (B, 67.4; NB, 45.3; B/NB, 48.4; and NC, 64.2%) when compared with intact islet grafts (88%; P < 0.05); however, islet-like aggregates with vascularization now showed an islet-specific glomerulus-like network of capillaries with a functional capillary density (498.5+/-49.1 to 601.4+/-124.0 cm[-1]) similar to that of intact islet grafts (644.3+/-26.8 cm[-1]). We conclude that the dissociation of pancreatic islets, followed by reaggregation of the purified endocrine cells to islet-like clusters (pseudoislets), delays the process of angiogenesis and revascularization after free transplantation; however, this does not influence the capacity to form an intact islet-specific microvasculature (angio-architecture), which appears to be independent from the cellular composition of pseudoislets.

Animals↗