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Biomedical subjects

M D Menger

Publications and source records attributed to M D Menger.

At least 19 recordsLinked to original sources
PubMed2001

Effects of hematocrit on cerebral microcirculation and tissue oxygenation during deep hypothermic bypass.

BACKGROUND: One rationale for hemodilution during hypothermic cardiopulmonary bypass (CPB) has been improved microcirculation. However, the optimal degree of hemodilution remains unclear. We therefore studied cerebral microcirculation and tissue oxygenation in a new intravital microscopic model at 3 different hematocrit (Hct) values. METHODS AND RESULTS: Three groups of 5 piglets with a cranial window over the parietal cortex underwent cooling at Hct of 10%, 20%, or 30%, followed by 1-hour deep hypothermic circulatory arrest (DHCA) and rewarming on CPB. For assessment of functional capillary density (FCD), plasma was labeled with fluorescein-isothiocyanate-dextran. Rhodamine-stained leukocytes were observed in postcapillary venules with analysis for adhesion and rolling. NADH, a natural intracellular fluorophore that increases during ischemia, was measured densitometrically during bypass and DHCA. FCD did not significantly differ from baseline during cooling in any group. However, during early reperfusion (5 minutes) after DHCA, the FCD was significantly higher in the Hct 30% group than in the Hct 10% group. Leukocyte adherence decreased in all groups during CPB and was only moderately increased at the end of the experiment. However, severe hemodilution (Hct 10%) was associated with a significantly greater number of rolling leukocytes relative to Hct 30%. CONCLUSIONS: Higher Hct does not impair cerebral microcirculation and reduces white cell/endothelial activation after deep hypothermic bypass and circulatory arrest. Severe hemodilution (Hct 10%) results in evidence of inadequate cerebral tissue oxygenation during the cooling phase of CPB. This study suggests that Hct of 30% is preferable relative to lower Hct values during hypothermic CPB, particularly if DHCA is used.

Animals↗
PubMed2001

Revascularization and microcirculation of freely grafted islets of Langerhans.

A considerable number of experimental studies have demonstrated that the reestablishment of an appropriate microvascular supply is an essential prerequisite for successful pancreatic islet transplantation. Freely transplanted islets show the first signs of angiogenesis (i.e., capillary sprout formation and protrusion) as early as 2 days after transplantation, and the entire vascularization process is completed after 10 to 14 days. Cryopreservation and culture of the isolated islets before transplantation and hyperglycemia of the transplant recipient seem not to affect the vascularization process essentially. In addition, immunosuppressive drugs, such as cyclosporin A and 15-deoxyspergualin, do not or only slightly inhibit revascularization of syngeneic islets; however, they are not able to prevent completely xenograft-induced microvascular perfusion failure. In contrast, novel immunosuppressants (e.g., RS-61443) or dietary supplementation of the antioxidant vitamin E were shown to prevent microvascular graft rejection almost completely, including leukocyte recruitment and capillary perfusion failure. Thus the development of novel strategies to improve posttransplant islet function should include concepts that accelerate the vascularization process and protect the newly formed microvasculature from rejection-mediated injury. The improvement of islet graft vascularization and the maintenance of adequate microvascular perfusion will contribute to the increased success of pancreatic islet transplantation.

Animals↗
PubMed2001

Hepatic arteriolo-portal venular shunting guarantees maintenance of nutritional microvascular supply in hepatic arterial buffer response of rat livers.

To elucidate the hepatic microvascular response upon the hepatic arterial buffer response (HABR), we analysed blood flow (ultrasonic flowprobes) of the hepatic artery (HA) and portal vein (PV), microcirculation (intravital microscopy), and tissue oxygenation (polarography) in anaesthetized Sprague-Dawley rats and re-evaluated the role of adenosine in mediating the HABR by using 8-phenyltheophylline as a competitive antagonist. 2. Upon restriction of PV blood flow to 11 +/- 3 % of baseline values, HA blood flow increased by a factor of 1.77 (P < 0.05), thus confirming HABR. Strikingly, red blood cell velocity and volumetric blood flow in terminal hepatic arterioles (THAs) did not increase but were even found to be slightly decreased, by 8 and 13 %, respectively. In contrast, red blood cell velocity and volumetric blood flow in terminal portal venules (TPVs) decreased to only 66 % (P < 0.05), indicating upstream hepatic arteriolo-portal venular shunting. As a consequence, red blood cell velocity and volumetric blood flow in sinusoids were found to be reduced to only 66-68 % compared with baseline (P < 0.05). Diameters of neither of those microvessels changed, thus excluding THA-, TPV-, and sinusoid-associated mechanisms of vasomotor control in HABR. 3. Tissue PO2 and hepatocellular NADH fluorescence remained unchanged, indicating HABR-mediated maintenance of adequate oxygen delivery, despite the marked reduction of total liver blood flow. Further, hepatic arteriolo-portal venular shunting guaranteed homogeneity of nutritive blood flow upon HABR, as given by an unchanged intra-acinar coefficient of variance of sinusoidal perfusion. 4. Pretreatment of animals with the adenosine antagonist 8-phenyltheophylline completely blocked the hepatic arterial buffer response with the consequence of decreased tissue oxygenation and increased heterogeneity of sinusoidal perfusion. 5. In conclusion, hepatic microhaemodynamics, in particular unchanged diameters of THAs, TPVs and sinusoids, during HABR indicate that reduction in resistance to HA flow is located upstream and functions via hepatic arteriolo-portal venular shunts resulting in equal distribution of microvascular blood flow and oxygen delivery under conditions of restricted PV blood supply.

Adenosine↗
PubMed2001

Microcirculatory derangements in acute pancreatitis.

During the past decade, a considerable number of experimental studies have confirmed the hypothesis that microcirculatory derangements play a pivotal role in the pathogenesis of acute pancreatitis, including the process of conversion from edematous to necrotizing injury. Predominant microcirculatory disorders are nutritive capillary perfusion failure, with the consequence of prolonged focal hypoxia or anoxia, and inflammation-associated microvascular leukocyte recruitment, CD11b- and intercellular adhesion molecule (ICAM)-1-mediated leukocyte-endothelial cell interaction and loss of endothelial integrity, which may result in both edema formation and necrosis. A variety of proinflammatory mediators, such as oxygen radicals, leukotrienes, platelet-activating factor, and interleukins, but also bradykinin and endothelins, seem to be involved in triggering the manifestations of these microcirculatory disorders. In contrast, the anti-inflammatory interleukin-10, as well as nitric oxide, are thought to be capable of protecting from these pancreatitis-associated microvascular injuries. This knowledge may be encouraging for the development of novel therapeutic strategies, aiming at the attenuation of microcirculatory disorders, and, thus, preventing tissue injury in acute pancreatitis.

Animals↗
PubMed2001

In vivo imaging of physiological angiogenesis from immature to preovulatory ovarian follicles.

To develop a model for the study of physiological angiogenesis, we transplanted ovarian follicles onto striated muscle tissue and analyzed the process of microvascularization in vivo using repeated fluorescence microscopy. Follicles were mechanically isolated from unstimulated as well as pregnant mare's serum gonadotropin (PMSG)- or PMSG/luteinizing hormone (LH)-stimulated Syrian golden hamster ovaries and were transplanted as free grafts into dorsal skinfold chambers of untreated or synchronized hamsters. Follicles lacking thecal cell layers did not vascularize regardless whether harvested from unstimulated or PMSG-stimulated animals, but underwent granulosa cell apoptosis, as indicated in vivo by nuclear condensation and fragmentation of bisbenzimide-stained follicular tissue. In contrast, all follicles at 48 hours after PMSG treatment with a multilayered thecal shell exhibited initial signs of angiogenesis within 3 days. Vascularization was completed within 7 to 10 days, comprising a dense glomerulum-like microvascular network. Nature and extent of vascularization of follicles harvested at 72 hours after either PMSG or PMSG/LH treatment did not notably differ from each other when transplanted into the respective synchronized animals. However, follicles with PMSG/LH treatment revealed significantly larger microvessel diameters and higher capillary blood perfusion compared to follicles with sole PMSG treatment, probably reflecting the adaptation to the increased functional demand upon the LH surge. Using the unique experimental approach of ovarian follicle transplantation in the dorsal skinfold chamber of Syrian golden hamsters, we could show in vivo the developmental stage-dependent vascularization of follicular grafts with sustained potential to meet their metabolic demand by increased blood perfusion.

Animals↗
PubMed2001

Heparin and the nonanticoagulant N-acetyl heparin attenuate capillary no-reflow after normothermic ischemia of the lung.

BACKGROUND: Ischemia-reperfusion injury of the lung frequently occurs after cardiopulmonary bypass, after pulmonary thromboendarterectomy, and especially after lung transplantation. Heparin is known to be protective in ischemia-reperfusion injury, but the risk for bleeding disorders may restrict its use in a variety of diseased conditions. Therefore, we tested the efficiency of nonanticoagulant N-acetyl (NA) heparin to protect from postischemic reperfusion injury of the lung. METHODS: Pentobarbital-anesthetized, mechanically ventilated Lewis rats were heparinized (100 IU/kg) before insertion of catheters. Additionally, animals received either heparin (200 IU/kg; n = 7), NA heparin (1.1 mg/kg; n = 7), or saline (control, n = 7) before ischemia. After normothermic ischemia for 50 minutes, the left lung was reperfused for 120 minutes, or until the death of the animal. The nonischemic right lung was excluded after 10 minutes of reperfusion. RESULTS: Survival rate at 120 minutes of reperfusion was 7 of 7 and 6 of 7 in the heparin and the NA-heparin group, but 0 in 7 in the control group (p < 0.01). At 30 minutes of reperfusion, PaO2, blood flow through the ascending aorta and mean systemic blood pressure were also significantly higher in the heparin and the NA-heparin group when compared with the control group (p < 0.05). Pulmonary vascular resistance was significantly lower in the heparin and the NA-heparin groups, and histologic examination of the lungs from these groups confirmed reperfusion of nutritive alveolar capillaries by the presence of red blood cells. Lack of red blood cells in the alveolar capillaries of lung specimens from the control group indicated failure of capillary reperfusion. CONCLUSIONS: Heparin and NA heparin exert similar protection against capillary no-reflow after normothermic ischemia of the lung. This implies that the protective effect of heparin is mediated by properties different from its anticoagulant activity. Thus the nonanticoagulant N-acetyl heparin may pose a safe new therapeutic approach in lung ischemia-reperfusion injury without increasing the risk of hemorrhagic complications.

Animals↗
PubMed2001

Differential effects of ET-1, ET-2, and ET-3 on pancreatic microcirculation, tissue integrity, and inflammation.

The differential effects of endothelin-1, -2, and -3 (ET-1, ET-2, and ET-3) on pancreatic microcirculation, pancreatic tissue integrity, and an initial inflammatory response, which are three distinct characteristics of acute necrotizing pancreatitis, were investigated in a dose-dependent manner in rats using in vivo microscopy. Red blood cell (RBC) velocity and functional capillary density (FCD) were estimated after topical superfusion of the pancreas with ET-1, ET-2, and ET-3 (100, 10, 1 pmol), revealing that ET-1 (100, 10, 1 pmol) or high ET-2 (100 pmol) and ET-3 (100 pmol) cause a dose-related deterioration of exocrine nutritive pancreatic blood flow. Analysis of pancreatic exocrine tissue damage employing the Spormann score displayed that the ET-mediated microcirculatory impairment was paralleled by dose-dependent tissue damage, which was significant compared to the control group (topical superfusion with 1 ml, saline solution 0.9%). Estimation of pancreatic postcapillary leukocyte accumulation by histomorphologically counting choracetate esterase (CAE) stained leukocytes in 50 high-power fields per animal demonstrated a significant increase in postcapillary accumulation of white blood cells, after topical administration of ET-1, ET-2, and ET-3 compared to controls. In contrast to ET-caused effects on microcirculation and tissue impairment, quantitative analysis of postcapillary leukocyte accumulation revealed the most pronounced effect after ET-2 administration but not after ET-1 administration. This demonstrates that ET-1, ET-2, and ET-3 are all able to mediate microcirculatory impairment, tissue damage, and inflammation. However, ET-3-induced damaging effects are less pronounced, while ET-1 most severely alters microcirculation and ET-2 preferentially induces leukocyte-dependent inflammation.

Animals↗
PubMed2001

Local heat-shock priming-induced improvement in microvascular perfusion in osteomyocutaneous flaps is mediated by heat-shock protein 32.

BACKGROUND: Stress conditioning is thought to improve microvascular free flap survival but the mechanisms of protection are not clear. The aim of this study was to determine whether local induction of heat-shock protein (HSP) 32 improves microvascular perfusion in transferred osteomyocutaneous flaps. METHODS: The hindlimb harvest region of osteomyocutaneous flaps in Wistar rats was subjected to stress conditioning by local heating (30 min, 42.5 degrees C) 24 h before microvascular flap transfer. In a second group of animals, after heat-shock priming, the action of HSP-32 was inhibited by tin protoporphyrin IX. Animals with unconditioned flaps served as controls. After transfer, the microcirculation of the muscle, cutaneous, subcutaneous and periosteal tissue of the flap was analysed quantitatively for 6 h using intravital fluorescence microscopy. RESULTS: Immunohistochemistry revealed that HSP-32 was detectable only after priming and not in unconditioned flaps. Priming did not alter functional capillary density or capillary red blood cell velocity compared with that in unconditioned flaps. However, heat-shock priming induced significant capillary dilatation (P < 0.05) and thus a substantial increase in capillary blood flow volume (P < 0.05) in all tissues of the transferred flaps. Inhibition of HSP-32 by tin protoporphyrin IX completely abolished the priming-induced improvement in capillary perfusion, as indicated by the lack of increased capillary diameters and volumetric blood flow. CONCLUSION: The present study demonstrated that stress conditioning by local heat-shock priming improves nutritive perfusion in osteomyocutaneous flaps by capillary dilatation, probably mediated through the vasoactive action of HSP-32.

Animals↗
PubMed2001

Reduction of inflammatory response in composite flap transfer by local stress conditioning-induced heat-shock protein 32.

BACKGROUND: The failure of composite flaps despite anastomotic patency is thought to be mediated by the inflammatory response within the microvasculature, which results from unavoidable surgical trauma and transfer-related ischemia-reperfusion. Evidence suggests that stress conditioning may improve flap survival; however, the molecular mechanisms of protection are far from being clear. Therefore, we analyzed whether stress conditioning-induced heat-shock protein 32 is effective to prevent the inflammatory response in transferred osteomyocutaneous flaps. METHODS: In a rat model, leukocyte-endothelial cell interaction and endothelial integrity disruption as early indicators of the inflammatory response were quantitatively analyzed in muscle, subcuticular tissue, and periosteum of microvascularly transferred osteomyocutaneous flaps by using intravital fluorescence microscopy. Twenty-four hours before flap transfer, stress conditioning was induced by local heating of the left hindlimb up to 42.5 degrees C for 30 minutes. In additional animals, stress conditioning-induced activity of heat-shock protein 32 was inhibited by tin protoporphyrin-IX. Unconditioned flaps served as controls. RESULTS: In all tissues analyzed, control flaps showed significant leukocyte adherence in postcapillary venules, increased intercellular adhesion molecule-1 (ICAM-1) expression, and endothelial integrity disruption, but a lack of heat-shock protein 32. In contrast, stress conditioning induced marked heat-shock protein 32 expression, which was associated with a significant reduction (P <.05) of leukocyte adherence, ICAM-1 expression, and endothelial hyperpermeability. The inhibition of heat-shock protein 32 by tin protoporphyrin-IX completely abolished the stress conditioning-induced amelioration of the inflammatory response in all tissues analyzed. CONCLUSIONS: Stress conditioning by local heat-shock priming reduces the inflammatory response in osteomyocutaneous flaps. The protective effect is predominantly mediated by the induction of heat-shock protein 32.

Animals↗
PubMed2001

Loss of physiologic hepatic blood flow control ("hepatic arterial buffer response") during CO2-pneumoperitoneum in the rat.

UNLABELLED: We analyzed whether a compensatory increase of hepatic arterial (HA) flow, known as the "hepatic arterial buffer response" (HABR), may serve for maintenance of liver blood supply during laparoscopy-associated portal venous (PV) flow reduction. We assessed HA and PV flow, as well as hepatic tissue oxygenation (PO2) during CO2-pneumoperitoneum in anesthetized and mechanically ventilated Sprague-Dawley rats (n = 7). Control animals (n = 7) without pneumoperitoneum, but tourniquet-induced PV flow reduction served to demonstrate physiologic HABR. Although stepwise tourniquet-induced reduction of PV flow to 20% of baseline values led to a significant (P < 0.05) increase of HA flow from 4.3 +/- 0.7 mL/min to 9.9 +/- 1.7 mL/min, stepwise intraabdominal pressure-induced decrease of PV flow was paralleled by a linear reduction of HA flow from 2.4 +/- 0.3 mL/min to 1.2 +/- 0.5 mL/min at 18 mm Hg intraabdominal pressure. This loss of HABR was sustained during a subsequent 2 h-period of CO2-pneumoperitoneum contrasting the 2 h of maintenance of HABR in controls. Hepatic tissue PO2 decreased during the 2 h-period of pressure- and tourniquet-induced PV flow reduction by 35% to 51%, respectively. On tourniquet release, all variables regained baseline values, whereas evacuation of the pneumoperitoneum allowed all variables except hepatic PO2 to return to baseline, indicating prolonged tissue hypoxia despite restored total liver blood flow in the Laparoscopic group. Concomitantly, increased liver enzyme activities reflected moderate tissue damage after 2 h of pneumoperitoneum. In conclusion, intraabdominal CO2-insufflation-induced hemodynamic alterations may impair tissue oxygenation and enzyme release, indicating the potential risk for hepatic tissue damage after prolonged periods of laparoscopic interventions. IMPLICATIONS: We investigated the effect of CO2-pneumoperitoneum on liver blood flow, hepatic tissue oxygenation (PO2) and liver enzyme release. CO2-insufflation reduces portal venous flow without a compensatory increase of hepatic arterial flow ("hepatic arterial buffer response"), resulting in reduced hepatic PO2 and increased ratios of serum alanine aminotransferase to serum aspartate aminotransferase.

Alanine Transaminase↗
PubMed2001

Lack of in vivo function of CD31 in vascular thrombosis.

A murine model of endothelial cell injury-based vascular thrombosis was used to test the role of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) in blood cell aggregate formation and vessel occlusion in vivo. Photochemically-induced thrombus formation was analyzed in detail using intravital fluorescence microscopy of individual microvessels in cremaster muscle preparations of CD31-deficient and wildtype mice. In venules, epi-illumination induced rapid thrombus formation with first platelet deposition after 0.56 +/- 0.11 min and complete vessel occlusion within 5.05 +/- 0.45 min. In arterioles, thrombus formation was markedly delayed with first platelet deposition after 3.03 +/- 0.47 min and complete vessel occlusion within 10.04 +/- 1.26 min. Kinetics of thrombus formation in both venules (first platelet deposition: 0.52 +/- 0.1 min; vessel occlusion: 5.03 +/- 0.52 min) and arterioles (first platelet deposition: 3.06 +/- 0.68 min; vessel occlusion: 10.02 +/- 1.38 min) of CD31-deficient mice was found almost identical compared with that in wildtype animals. Tail bleeding time was 233 +/- 24 s in wildtype and 243 +/- 32 s in CD31-deficient mice. Moreover, CD31-deficient and wildtype mice revealed comparable interaction of leukocytes to endothelium. This study shows for the first time in vivo that CD31 is not critically involved in blood cell thrombus formation upon endothelial cell injury.

Animals↗
PubMed2000

Targeting angiogenesis inhibits tumor infiltration and expression of the pro-invasive protein SPARC.

The solid growth of high-grade glioma appears to be critically dependent on tumor angiogenesis. It remains unknown, however, whether the diffuse infiltration of glioma cells into healthy adjacent tissue is also dependent on the formation of new tumor vessels. Here, we analyze the relationship between tumor angiogenesis and tumor cell infiltration in an experimental glioma model. C6 cells were implanted into the dorsal skinfold chamber of nude mice, and tumor angiogenesis was monitored by intravital fluorescence videomicroscopy. Glioma infiltration was assessed by the extent of tumor cell invasion into the adjacent chamber tissue and by expression of SPARC, a cellular marker of glioma invasiveness. To test the hypothesis that glioma angiogenesis and glioma infiltration are codependent, we assessed tumor infiltration in both the presence and the absence of the angiogenesis inhibitor SU5416. SU5416 is a selective inhibitor of the VEGF/Flk-1 signal-transduction pathway, a critical pathway implicated in angiogenesis. Control tumors demonstrated both high angiogenic activity and tumor cell invasion accompanied by strong expression of SPARC in invading tumor cells at the tumor-host tissue border. SU5416-treated tumors demonstrated reduced vascular density and vascular surface in the tumor periphery accompanied by marked inhibition of glioma invasion and decreased SPARC expression. A direct effect of SU5416 on glioma cell motility and invasiveness was excluded by in vitro migration and invasion assays. These results suggest a crucial role for glioma-induced angiogenesis as a prerequisite for diffuse tumor invasion and a possible therapeutic role for anti-angiogenic compounds as inhibitors of both solid and diffuse infiltrative tumor growth.

Angiogenesis Inhibitors↗
PubMed2000

Microvascular consequences of thrombosis in small venules: an in vivo microscopic study using a novel model in the ear of the hairless mouse.

Little is known of the development of chronic microvascular alterations following small vessel thrombosis, which is probably due to the lack of appropriate experimental models. Herein we report the first results on thrombosis-associated long-term changes of microvascular permeability and vessel tortuosity and diameter and blood perfusion using the ear of the hairless mouse, and intravital fluorescence microscopy. Thrombosis was induced photochemically in small venules (diameter: 75 to 100 microm) using light/dye exposure (fluorescein isothiocyanate-dextran 150,000), and the microcirculation compromised by the blockade of blood drainage was analyzed before and 30 minutes after induction of thrombosis as well as repeatedly over a 28-day observation period. Thrombus formation resulted in a marked increase (p<0.05) of microvascular permeability (0.85+/-0.11) when compared with baseline values (0.46+/-0.04). Permeability remained elevated (p<0.05) at days 1 (0.67+/-0.07), 3 (0.58+/-0.02), and 7 (0.60+/-0.06), but returned to normal after 28 days (0.43+/-0.03). Tortuosity, diameter, and red blood cell velocity of venular segments, located upstream of thrombus formation, were found unchanged during the entire 28-day observation period. This was probably due to the fact that blood flow from the thrombosis-affected tissue was frequently drained into nonaffected tissue via preexisting "through-fare" channels, serving as venulo-venular collaterals. In accordance, in 10 to 20% of these venular segments the direction of blood perfusion was found changed, while those changes were only rarely observed in venular vessel segments of the nonthrombotic contralateral ears. We conclude that thrombosis in small cutaneous venules is primarily characterized by an increased vascular permeability, reflecting an inflammatory response, similar to what is known from thrombophlebitis in patients. The model presented herein may be a versatile tool to study pathogenesis of chronic microcirculatory derangements in microthrombosis and their prevention by novel therapeutic strategies.

Animals↗
PubMed2000

Warm preflush with streptokinase improves microvascular procurement and tissue integrity in liver graft retrieval from non-heart-beating donors.

BACKGROUND: Apart from the warm ischemic insult, integrity of liver grafts from non-heart-beating donors (NHBD) is additionally affected by microvascular alterations including erythrocyte aggregation and thrombus formation, which might hamper appropriate equilibration of the preservation solution to the grafts' microvasculature precluding cold preservation. Thus, the objective of our study was to characterize microvascular perfusion quality of University of Wisconsin (UW) solution during initial flushout of livers from NHBD rats, and to analyze the effects of an additional warm preflush with Ringer's lactated solution (RL) and with RL containing streptokinase (SK). METHODS: Cardiocirculatory arrest was induced by phrenotomy. Subsequent to 30 min of warm ischemia, livers were perfused via an aortic catheter by gravity of 100 cm H2O either with 4 degrees C 100 ml UW solution (UW, n=7), or with 25 degrees C 30 ml RL preflush followed by 4 degrees C 100 ml UW solution (RL+UW, n=7), or with 25 degrees C 30 ml SK- (7500 IU) containing RL preflush and 4 degrees C 100 ml UW solution (SK/RL+UW, n=6). Liver microperfusion was quantified using in situ fluorescence epi-illumination microscopy. Liver microcirculation of sham-operated living animals (n=4) served as controls. Enzyme release after a 24-hr cold preservation period was used as an indicator of graft integrity. RESULTS: After 30 min of warm ischemia, microvascular perfusion of UW solution was found markedly altered when compared with that of sham-operated living controls, as indicated by a significant reduction (P<0.05) of acinar and sinusoidal perfusion. Preflush with RL (RL+UW) only slightly attenuated the acinar and sinusoidal perfusion deficits, whereas the addition of SK to RL (SK/RL+UW) resulted in a significant improvement of microvascular graft perfusion (P<0.05). Accordingly, the increased enzyme release observed in solely UW-flushed livers after 24 hr cold preseravtion was only slightly influenced by preflush with RL, but markedly attenuated (P<0.05) by pre-flush with RL containing SK. CONCLUSION: The additive fibrinolytic therapy using SK is effective to improve microvascular procurement of livers after warm ischemia and may thus represent a promising approach to attenuate parenchymal cell injury in liver graft retrieval from NHBD.

Adenosine↗
PubMed2000

Exocrine contamination of isolated islets of Langerhans deteriorates the process of revascularization after free transplantation.

BACKGROUND: We investigated the influence of exocrine tissue contamination on the process of vascularization of isolated pancreatic islets of Langerhans after free transplantation into Syrian golden hamsters. METHODS: After isolation by a modified collagenase digestion technique, a total of 45 individual islets contaminated with exocrine tissue were transplanted syngeneically into striated muscle of dorsal skinfold chambers of nine animals. Sixty-six purified islet grafts transplanted into nine additional animals served as controls. Islet engraftment as well as the process of angiogenesis and revascularization were analyzed at days 3, 5, 9, and 13 after transplantation using intravital fluorescent microscopic techniques. RESULTS: Islet grafts contaminated with exocrine tissue showed a significantly (P<0.05) lower take rate initially after transplantation when compared with purified islet grafts. In addition, functional capillary density, which served as an indicator of graft vascularization, was found significantly (P<0.05) decreased in contaminated compared with purified islets. Exocrine tissue contamination was further associated with marked leukocyte-endothelial cell interaction within the grafts' postcapillary venules, which finally resulted in six of nine animals in an overwhelming unspecific inflammation of the transplantation site with successive loss of the islet transplants. CONCLUSIONS: These findings support the view that exocrine tissue contamination is detrimental for the process of angiogenesis and vascularization of freely transplanted pancreatic islets when grafted to a confined site such as striated muscle tissue.

Animals↗