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Biomedical subjects

M D Menger

Publications and source records attributed to M D Menger.

At least 73 records · Page 4Linked to original sources
PubMed2000

Heparin and phentolamine combined, rather than heparin alone, improves hepatic microvascular procurement in a non-heart-beating donor rat-model.

Improvement of organ procurement from non-heart-beating donors (NHBDs) could increase the donor organ pool for liver transplantation. Whether anti-coagulative and anti-vasospastic substances can improve hepatic microvascular preservation from NHBDs is unknown. In donor rats which were pretreated with either heparin (n = 6) or heparin combined with phentolamine (n = 7) 10 min prior to cardiac arrest, the extent and homogeneity of hepatic microvascular reperfusion was assessed at the end of a 60-min period of cardiac arrest using in situ fluorescence microscopy. Non-pretreated animals with cardiac arrest for 60 min served as controls (n = 6). In the non-treated NHBDs, arterial gravity perfusion of 100 cm H2O with HTK-solution led to a hepatic acinar reperfusion of only approximately 22 % with a remarkably diminished sinusoidal density. Application of heparin prior to cardiac arrest resulted in a two-fold, but insignificant increase of acinar perfusion and sinusoidal density with a still considerable heterogeneity of both parameters. Livers of NHBDs that additionally received phentolamine exhibited significantly increased values of both acinar perfusion and sinusoidal density. Phentolamine was found to reduce heterogeneity of organ microperfusion. Thus, our results indicate that the combined application of heparin and phentolamine is a useful additive for optimizing the quality of organs harvested from NHBDs.

Alanine Transaminase↗
PubMed2000

Significance of hepatic arterial responsiveness for adequate tissue oxygenation upon portal vein occlusion in cirrhotic livers.

We investigated sinusoidal blood flow and hepatic tissue oxygenation during portal vein occlusion in cirrhotic rat livers to examine the effect of cirrhosis on the properties of hepatic microvascular blood flow regulation. After 8 weeks of CCl4/phenobarbital sodium treatment to induce cirrhosis Sprague-Dawley rats were prepared surgically to allow assessment of portal venous and hepatic arterial inflow using miniaturized flow probes with simultaneous analysis of hepatic microcirculation and tissue oxygenation by fluorescence microscopy and polarographic oxymetry. Age-matched noncirrhotic animals served as controls. Upon portal vein occlusion in cirrhotic livers (flow reduction to < 20%), hepatic arterial blood flow increased 1.5-fold (61 +/- 8 ml/min per 100 g liver) of baseline (40 +/- 7 ml/min per 100 g liver), reflecting an appropriate hepatic arterial buffer response (HABR), similarly as seen in control livers. The net result was a reduction in total liver inflow from 90 +/- 12 to 72 +/- 11 ml/min per 100 g liver, which was associated with a significant decrease in both sinusoidal red blood cell velocity and volumetric blood flow to approx. 71% and 76% of baseline values. However, portal vein occlusion did not cause a deterioration in hepatic tissue pO2 (11 +/- 3 vs. 10 +/- 3 mmHg at baseline). Sinusoidal diameters were found unchanged, disproving a major role of the sinusoidal tone in the regulation of HABR. Microvascular response of cirrhotic livers did not generally differ from that in noncirrhotic livers upon portal inflow restriction. We conclude that HABR in cirrhotic livers operates sufficiently to meet the liver tissue oxygen demand, most probably by an increased relative contribution of arterial perfusion of hepatic sinusoids.

Animals↗
PubMed2000

Acceleration of wound healing by topical drug delivery via liposomes.

BACKGROUND: Despite intensive research, impaired wound healing remains a considerable complication. Therefore, topically applied liposome-encapsulated buflomedil hydrochloride was investigated for its ability to improve wound repair in normal (n=16) and ischemic (n=16) skin tissue. METHODS: Experiments were performed using the wound healing model of the ear of hairless mice. Standardized skin wounds (4.25 mm(2)) were created by circular excision of the epidermal layer and the subcutaneous tissue. Liposomes were applied daily until complete neovascularization of the wound occurred. Tissue regeneration by complete epithelialization and neovascularization of the wound area, microcirculatory parameters, and leukocyte-endothelium interaction were investigated by means of intravital microscopy. Microvascular perfusion was assessed by laser-Doppler flowmetry. RESULTS: Topical application of buflomedil liposomes led to a significantly (P<0.05) accelerated wound closure in both normal (9.6+/-0.7 days) and ischemic (13.4+/-0.1 days) skin tissue compared with animals that were treated with unloaded liposomes (controls; 13.1+/-0.8 days; 15.3+/-0.6 days). Complete neovascularization of the wound was also enhanced (P<0.05) in buflomedil-treated animals (normal tissue 18.8+/-0.4 days; ischemic tissue 19.6+/-0.7 days) compared with controls (20.6+/-0.6 days; 22. 6+/-1.2 days). CONCLUSION: These data suggest that buflomedil-loaded liposomes might be of beneficial use for clinical wound care.

Administration, Cutaneous↗
PubMed2000

Experimental development and validation of a technique for lumboendoscopic anterior fusion of lumbar spine fractures: comparison of endoscopic and open surgery in a live porcine model.

BACKGROUND: Using a porcine model, this study describes the feasibility of a lumboendoscopically guided approach to the lumbar spine for anterior interbody fusion, and compares the results with that of the open procedure. The objectives of this study were to develop a minimally invasive approach to the lumbar spine for anterior fusion in pigs, and to test the validity and safety of the procedure in this porcine model. Besides posterior stabilization, considerable number of thoracolumbar spine (Th12-L5) fractures require intervention for anterior fusion to prevent loss of height of the injured segment and kyphotic deformation. Because anterior fusion needs major surgery (thoracophrenolumbotomy for Th12-L1), which is associated with high morbidity, this study aimed to develop a less traumatic minimally invasive approach. METHODS: Six pigs under balanced anesthesia were used to study the feasibility of the lumboendoscopic approach for bisegmental fusion (iliac crest bone block and dynamic compression plate) from Th15 to L6. In an additional six animals, lumboendoscopic fusion was performed at the level of diaphragm insertion (Th14-Th16), representing Th12-L1 in patients. For comparative analysis, six animals undergoing open thoracophrenolumbotomy and anterior Th14-Th16 fusion served as control subjects. RESULTS: Endoscopic anterior fusion could be successfully performed at all levels of the thoracolumbar spine without major complications. In three cases, unintended opening of the peritoneal cavity was observed, however, without the operative procedure being affected. Comparative analysis revealed a significantly longer p < 0.01 operation time (126 +/- 6.5 min) and increased femoral vein pressure (11.3 +/- 0.7 mmHg) in animals undergoing endoscopic surgery (open procedure, 76.0 +/- 11.6 min and 5.2 +/- 0.5 mmHg). However, the microvascular blood supply (perfusion) to the distal extremities, as assessed by laser Doppler flowmetry, was not affected. CONCLUSIONS: Our study demonstrates that lumboendoscopic anterior spine fusion in pigs is feasible at all levels from Th14 to L6, and can be performed in an acceptable operation time without major complications.

Animals↗
PubMed2000

Reliable noninvasive parameters for early detection of cardiopulmonary compromise induced by carbon dioxide thoracoretroperitoneum in minimally invasive thoracolumboendoscopic spine surgery.

BACKGROUND: Using a novel endoscopic retroperitoneal approach for thoracolumbar anterior spine fusion, we examined the cardiopulmonary effects of the inevitably associated carbon dioxide (CO2) thoracoretroperitoneum and evaluated noninvasive parameters, which may provide early and adequate recognition of cardiopulmonary dysfunction. METHODS: Under balanced anesthesia and paralysis, six pigs subjected to endoscopic CO2 thoracoretroperitoneal spine fusion underwent extensive pulmonary and hemodynamic online monitoring throughout the operative procedure. Open thoracophrenolumbotomy in six pigs served as a control procedure. RESULTS: In contrast to unchanged cardiopulmonary parameters during open thoracolumbar spine surgery, CO2 thoracoretroperitoneum caused significant hypercapnia, hypoxia, and acidemia with concomitant tachycardia, pulmonary hypertension, and systemic hypotension. Ventilatory adjustment, CO2 evacuation, or both promptly reversed the cardiopulmonary effects. Noninvasively assessed end-tidal CO2, peak respiratory pressure, and heart rate were early clues for detecting the tension pneumothorax-like cardiopulmonary dysfunction, as indicated by a significant correlation with the invasively assessed pulmonary hemodynamic parameters and arterial blood gases. CONCLUSIONS: During endoscopic thoracolumbar spine fusion, CO2 thoracoretroperitoneum induces cardiopulmonary dysfunction, which, however, can be detected reliably by changes in end-tidal CO2, peak respiratory pressure, and heart rate, and which can be corrected immediately by appropriate ventilatory adjustments. Therefore, endoscopic CO2 thoracoretroperitoneal spine fusion might not necessarily require extraordinarily extensive and invasive monitoring of systemic and pulmonary hemodynamics, but ventilatory adjustment and intrathoracic pressure evacuation should be readily available to reexpand the lung, and to facilitate rapid normalization of hemodynamic conditions.

Animals↗
PubMed2000

Anti-ICAM-1 blockade reduces postsinusoidal WBC adherence following cold ischemia and reperfusion, but does not improve early graft function in rat liver transplantation.

BACKGROUND/AIM: The present in vivo study investigated the impact of a monoclonal antibody directed against the intercellular adhesion molecule-1 (ICAM-1) on initial microvascular reperfusion injury after liver transplantation. METHODS: Orthotopic, syngeneic liver transplantation including arterial reconstruction was performed in male Lewis rats after 24 h graft storage in University of Wisconsin (UW) solution at 4 degrees C. Animals received either an anti-ICAM-1 antibody (n=7), an IgG1 control antibody (n=8) or saline only (n=7). Hepatic microvascular alterations during the initial 90 min of reperfusion were assessed using intravital fluorescence microscopy. Early graft dysfunction was determined by analysis of bile flow. RESULTS: After treatment with anti-ICAM-1 mAb, hepatic microvascular perfusion was found improved when compared with that of IgG1- and saline-treated controls. In addition, anti-ICAM-1 mAb effectively reduced the number of permanently adherent white blood cells in postsinusoidal venules (284.4+/-59.1 mm(-2) vs IgG1: 371.9+/-26.7 mm(-2) and saline: 431.8+/-46.4 mm(-2); p<0.05). In contrast, the number of stagnant white blood cells in sinusoids was higher (p<0.05) in liver grafts with blocked ICAM-1 (320.6+/-17.2 mm(-2)) compared with that of IgG1- (215.2+/-11.1 mm(-2)) and saline-treated controls (226.4+/-14.0 mm(-2)). Measurement of hepatic uptake of fluorescent-labeled latex particles did not reveal significant differences in phagocytic activity. Finally, bile flow also did not differ between the three groups studied. CONCLUSION: Together these results indicate that ICAM-1 is involved in the process that mediates white blood cells adherence in postsinusoidal venules, whereas in hepatic sinusoids other mechanisms apart from ICAM-1-mediated white blood cells adherence seem to be fundamental for posttransplant white blood cells accumulation. Our data further suggest that white blood cells adherence in postsinusoidal venules via ICAM-1 does not make a major contribution to the pathogenesis of early cold ischemia/reperfusion injury after liver transplantation.

Animals↗
PubMed2000

Lymphocyte function antigen 1 (LFA-1) mediates early tumour necrosis factor alpha-induced leucocyte adhesion in venules.

A co-ordinated expression of specific adhesion molecules regulates leucocyte-endothelium interactions in the microcirculation. In the present study, we used intravital microscopy of the cremaster muscle in CD11a gene-targeted mice to examine the role of lymphocyte function antigen 1 (LFA-1, CD11a/CD18) in tumour necrosis factor alpha (TNF-alpha)-induced leucocyte rolling and firm adhesion in venules. We found that 30 min after TNF-alpha administration leucocyte rolling was unchanged compared with phosphate-buffered saline (PBS)-treated mice and similar in LFA-1-deficient and wild-type animals. In contrast, firm leucocyte adhesion in venules increased by almost 10-fold following 30 min of TNF-alpha challenge in LFA-1-expressing animals, whereas no increase was observed in LFA-1-deficient mice. Four hours after intrascrotal administration of TNF-alpha, venular leucocyte adhesion was found to be markedly increased, but similar in extent to LFA-1-deficient and wild-type mice. Histological examination of haematoxylin-eosin-stained tissue sections revealed that approximately 90% of the leucocytes in the TNF-alpha-stimulated venules in both wild-type and LFA-1-deficient mice were polymorphonuclear. Taken together, our functional in vivo data demonstrate that LFA-1 is an important adhesion molecule in early TNF-alpha-induced venular leucocyte adhesion.

Animals↗
PubMed2000

The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and L-selectin function in vivo.

BACKGROUND: Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. MATERIALS AND METHODS: For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. RESULTS: We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. CONCLUSIONS: Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L-selectin function but may instead be related to the anticoagulative capacity of fucoidan.

Animals↗
PubMed2000

Complete shutdown of microvascular perfusion upon hepatic cryothermia is critically dependent on local tissue temperature.

Since microvascular dysfunction with complete circulatory arrest and, thus, prolongation of tissue ischaemia is considered a potential mechanism for cell necrosis following hepatic cryosurgery, we determined the temperature necessary for induction of complete nutritive perfusion failure in cryothermia-treated rat livers. After localization of the cryoprobe with seven thermocouples and application of a single or double freeze-thaw cycle, in vivo fluorescence microscopy of the cryoinjured left lobe was performed over a 2-h period using a computer-controlled stepping motor, which guaranteed analysis of the identical liver tissue segments with exact allocation of the thermocouples and thus determination of tissue temperature. Cryothermia resulted in a central non-perfused part of injury, surrounded by a heterogeneously perfused peripheral zone. The non-perfused area after single and double freezing continuously increased over the first 90-min period due to a successive shutdown of perfusion within the peripheral border zone. Analysis of the thermocouples' temperature at the end of freezing revealed the 0 degrees C-front at 11.7 mm (single freeze-thaw cycle) and 12.1 mm (double freeze-thaw cycle) distant from the centre of the cryoprobe, which exactly corresponds with the initial (30 min) expansion of the area with nutritive perfusion failure. The increased non-perfused tissue area at 2 h conformed a critical border temperature between 8.29 +/- 1.63 degrees C and 9.07 +/- 0.24 degrees C. From these findings, we conclude that freezing of liver tissue to temperatures of at least < 0 degrees C causes complete/irreversible perfusion failure, which consequently will result in cell death and tissue necrosis, and may thus be supposed as a prerequisite for the safe and successful application of cryosurgery in hepatic tumour ablation.

Animals↗
PubMed2000

Establishment of an immunocompetent nipple valve anastomosis to prevent faecal reflux after ileocolic resection in dogs.

OBJECTIVE: To construct an immunocompetent nipple valve anastomosis (NVA) to exclude faecal reflux and compare it with an end-to-end anastomosis to see if it would prevent recurrent inflammation caused by intraluminal bacterial antigens in Crohn's disease. DESIGN: Laboratory study. SETTING: Teaching hospital, Germany. ANIMALS: Two groups of six beagle dogs each of which had NVA or end-to-end anastomosis. INTERVENTIONS: Construction of a NVA by stapling the telescoped nipple, and replacing the ileal mucosa on the valve by colonic mucosa; end-to-end anastomosis. MAIN OUTCOME MEASURES: Radiological, bacteriological, angiographic, and morphometric results. RESULTS: Absolute retrograde pressure-competence and free orthograde permeability of the NVA resulted in significantly lower intestinal bacterial counts compared with the end-to-end anastomosis (p < 0.05). Transposition of colonic mucosa was successful as demonstrated by revascularisation from the ileal nipple and looked normal on morphometry. CONCLUSION: If NVA were constructed in patients with Crohn's disease, recurrences should be prevented, which would verify the immunopathogenetic hypothesis of new inflammation.

Anastomosis, Surgical↗
PubMed2000

The thrombin antagonist hirudin fails to inhibit endotoxin-induced leukocyte/endothelial cell interaction and microvascular perfusion failure.

Besides its central role in coagulatory pathways, thrombin is known to be a key mediator of macrophage and granulocyte activation in vitro. During recent years the concept of thrombin inhibition by the specific thrombin inhibitor, hirudin, has been established to treat septic disorders. Since basic mechanisms of sepsis include leukocyte/endothelial cell interaction and deterioration of capillary perfusion, we hypothesized that hirudin modulates leukocyte activation and microvascular injury. Severe endotoxemia was induced in Syrian hamsters by intravenous administration of endotoxin (lipopolysaccharide [LPS], E. coli, 2mg/kg) at 0 h. Hirudin (0.25 mg/kg/h) was substituted intravenously during the 4 h after the induction of endotoxemia (n = 7, hirudin). In control animals (n = 6, control) LPS was given without hirudin substitution. In skinfold chamber preparations leukocyte/endothelial cell interaction and functional capillary density (FCD, measure of capillary perfusion) were analyzed during a 24-h period after LPS injection using intravital fluorescence microscopy. Hirudin effectively normalized thromboplastin time and antithrombin activity when compared to controls (P < 0.05, ANOVA). However, hirudin did not attenuate LPS-induced arteriolar and venular leukocyte adherence, and even tended to increase leukocyte adherence after 24 h (P > 0.05, MANOVA). In parallel, addition of hirudin led to a significant deterioration of FCD over time when compared to controls (hirudin: baseline = 171 +/- 19 cm(-1) versus 16 +/- 9 at 24 h; control: baseline = 150 +/- 20 cm(-1) versus 62 +/- 18 at 24 h; P < 0.05). The fall in FCD in hirudin animals was associated with a significant increase of wet-to-dry weight ratios in lung, kidney, muscle, and small intestine (P < 0.05 versus control, ANOVA). Thus our study does not indicate a protective effect of hirudin on microcirculation during endotoxemia, despite an improvement of coagulatory parameters. This result may at least in part explain the lack of efficacy of hirudin on lethality during endotoxemia and sepsis.

Animals↗
PubMed2000

Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway.

Antithrombin (AT) is known as the most important natural inhibitor of thrombin activity and has been shown to improve distinct clinical parameters during the course of septic (endotoxin)-induced multiple organ dysfunction. We hypothesized that AT acts by inhibiting leukocyte activation and microvascular injury via the promotion of endothelial release of PGI(2), and therefore, we studied the effects of AT on leukocyte/endothelial cell interaction and microvascular perfusion during endotoxemia. In a skinfold preparation of Syrian hamsters, severe endotoxemia was induced by repeated administration of endotoxin intravenously [lipopolysaccharide (LPS), Escherichia coli, 2 mg/kg] at 0 and 48 h. AT (250 IU/kg) was administered intravenously at 0, 24, and 48 h (n = 6, AT group). In control animals (n = 5, control), LPS was given without AT supplementation. By intravital fluorescence microscopy, leukocyte-endothelial cell interaction and functional capillary density (FCD; measure of capillary perfusion) were analyzed during a 72-h period after the first LPS injection. AT significantly attenuated LPS-induced arteriolar and venular leukocyte adherence after both the first and the second LPS injection [P < 0.01, measures analysis of variance (MANOVA)]. In parallel, AT was effective in preventing LPS-induced depression of FCD after the first and the second LPS administration (P < 0.05, MANOVA). By pretreatment with the cyclooxygenase inhibitor indomethacin (n = 6), effects of AT on leukocyte adherence and FCD were found completely abolished. Thus our study indicates that AT exerts its beneficial effects in endotoxemia by reducing leukocyte-endothelial cell interaction and microvascular perfusion failure probably via liberation of prostacyclin from endothelial cells.

Animals↗
PubMed2000

Impact of intrinsic blood flow regulation in cirrhosis: maintenance of hepatic arterial buffer response.

The hepatic arterial buffer response (HABR) effectively controls total blood perfusion in normal livers, but little is known about blood flow regulation in cirrhosis. We therefore studied the impact of HABR on blood perfusion of cirrhotic livers in vivo. After 8-wk CCl(4) treatment to induce cirrhosis, 18 anesthetized rats (and 18 noncirrhotic controls) were used to simultaneously assess portal venous and hepatic arterial inflow with miniaturized ultrasonic flow probes. Stepwise hepatic arterial blood flow (HAF) or portal venous blood flow (PVF) reduction was performed. Cirrhotic livers revealed a significantly reduced total hepatic blood flow (12.3 +/- 0.9 ml/min) due to markedly diminished PVF (7.3 +/- 0.8 ml/min) but slightly increased HAF (5.0 +/- 0.6 ml/min) compared with noncirrhotic controls (19.0 +/- 1.6, 15.2 +/- 1.3, and 3.8 +/- 0.4 ml/min). PVF reduction caused a significant HABR, i.e., increase of HAF, in both normal and cirrhotic livers; however, buffer capacity of cirrhotic livers exceeded that of normal livers (P < 0.05) by 1. 7- to 4.5-fold (PVF 80% and 20% of baseline). Persistent PVF reduction for 1, 2, and 6 h demonstrated constant HABR in both groups. Furthermore, HABR could be repetitively provoked, as analyzed by intermittent PVF reduction. HAF reduction did not induce changes of portal flow in either group. Because PVF is reduced in cirrhosis, the maintenance of HAF and the preserved HABR must be considered as a protective effect on overall hepatic circulation, counteracting impaired nutritive blood supply via the portal vein.

Animals↗