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Biomedical subjects

B Vollmar

Publications and source records attributed to B Vollmar.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2000

Effect of warm ischemia time and organ perfusion technique on liver microvascular preservation in a non-heart-beating rat model.

BACKGROUND: Current organ shortage has led to a reconsideration of non-heart-beating cadaveric donation. METHODS: We assessed the effectivity of dual, i.e., arterial and portal-venous versus exclusive, arterial gravity perfusion for procurement of rat livers after 30 min and 60 min of cardiac arrest, analyzing the rate and homogeneity of microvascular perfusion by in situ fluorescence microscopy. RESULTS: After 30 min of cardiac arrest, a nearly 100% recovery of acinar perfusion with a sinusoidal density not significantly different from that of normal, nonischemic livers was achieved by dual gravity perfusion. Prolongation of cardiac arrest to 60 min caused an almost 50% deficit of acinar and sinusoidal perfusion (P<0.05) with a concomitant 2-3-fold increase of heterogeneity of hepatic microperfusion. Regardless of the warm ischemic time period, dually perfused livers exhibited significantly (P<0.05) higher rates of both acinar and sinusoidal perfusion with increased homogeneity of microcirculation when compared with exclusive arterial perfusion. CONCLUSION: These data underline the need and benefit of dual perfusion as well as the limitation of warm ischemic tolerance to 30 min for safe liver procurement of non-heart-beating donors.

Animals↗
PubMed2000

Striated muscle microvascular response to silver implants: A comparative in vivo study with titanium and stainless steel.

Local microvascular perfusion is the primary line of defense of tissue against microorganisms and plays a considerable role in reparative processes. The impairment of the microcirculation by a biomaterial may therefore have profound consequences. Silver is known to have excellent antimicrobial activity and, although regional and systemic toxic effects have been described, silver is regularly discussed as an implant material in bone surgery. Because little is known about the influence of silver implants on the adjacent host tissue microvasculature, we studied in vivo nutritive perfusion and leukocytic response, and compared these results with those of the conventionally used materials titanium and stainless steel. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, the implantation of a commercially pure silver sample led to a distinct and persistent activation of leukocytes combined with a marked disruption of the microvascular endothelial integrity, massive leukocyte extravasation, and considerable venular dilation. Whereas animals with stainless-steel implants showed a moderate increase in these parameters with a tendency to recuperate, titanium implants caused only a transient increase of leukocyte-endothelial cell interaction within the first 120 min and no significant change in macromolecular leakage, leukocyte extravasation and venular diameter. After 3 days, five of six preparations with silver samples showed severe inflammation and massive edema. Thus, the use of silver as an implant material should be critically judged despite its bactericidal properties. The implant material titanium seems to be well tolerated by the local vascular system and currently represents the golden standard.

Animals↗
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

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

Transcriptional activation of heme oxygenase-1 and its functional significance in acetaminophen-induced hepatitis and hepatocellular injury in the rat.

BACKGROUND/AIM: Glutathione depletion contributes to acetaminophen hepatotoxicity and is known to induce the oxidative stress reactant heme oxygenase-1. The metabolites of the heme oxygenase pathway, biliverdin, carbon monoxide, and iron may modulate acetaminophen toxicity. The aim of this study was to assess cell-type specific expression of heme oxygenase-1 and its impact on liver injury and microcirculatory disturbances in a model of acetaminophen-induced hepatitis. METHODS: Gene expression of heme oxygenase-1 was studied by Northern- and Western analysis as well as immunohistochemistry. The time course of heme oxygenase-1 and -2, cytokine-induced neutrophil chemoattractant-1, and intercellular adhesion molecule-1 was studied by Northern analysis. DNA-binding activity of nuclear factor-kappaB was determined by electrophoretic mobility shift assay. Sinusoidal perfusion and leukocyte-endothelial interactions were assessed by intravital microscopy. RESULTS: Acetaminophen caused a moderate sinusoidal perfusion failure (-15%) and infiltration of neutrophils along with activation of nuclear factor-kappaB and intercellular adhesion molecule-1 and cytokine-induced neutrophil chemoattractant-1 mRNAs. Induction of heme oxygenase-1 mRNA and protein (approximately 30-fold) in hepatocytes and non-parenchymal cells paralleled the inflammatory response. Blockade of heme oxygenase activity with tin-protoporphyrin-IX abrogated acetaminophen-induced hepatic neutrophil accumulation and nuclear factor-kappaB activation, but failed to affect sinusoidal perfusion and liver injury. CONCLUSIONS: The inflammatory response associated with acetaminophen hepatotoxicity is modulated by the parallel induction of the heme oxygenase-1 gene. However, heme oxygenase-1 has no permissive effect on sinusoidal perfusion and does not affect liver injury in this model. These data argue against a central role of nuclear factor-kappaB activation and neutrophil infiltration as perpetuating factors of liver injury in acetaminophen toxicity.

Acetaminophen↗
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

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↗