Synergistic effects of brain death and liver steatosis on the hepatic microcirculation.

Background: The routine transplantation of steatotic livers could potentially mitigate the donor shortage, but so far is associated with a high rate of graft dysfunction. Steatosis and brain death have been perceived as independent risk factors, but they may synergistically target the hepatic microcirculation. This study compares the effects of brain death on the microcirculation of steatotic and normal livers.

Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation.

Aim: To investigated the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.

Methods: Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls, n=8) or GSH (50 or 100 micromol/(h/kg), n=5 each) was continuously administered via the jugular vein.

Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia.

Objective: To evaluate the potential of postischemic intravenous infusion of the endogenous antioxidant glutathione (GSH) to protect the liver from reperfusion injury following prolonged warm ischemia.

Background Data: The release of reactive oxygen species (ROS) by activated Kupffer cells (KC) and leukocytes causes reperfusion injury of the liver after warm ischemia. Therefore, safe and cost-effective antioxidant strategies would appear a promising approach to prevent hepatic reperfusion injury during liver resection, but need to be developed.

[Effect of adenosine on intravascular accumulation of leukocytes and tissue damage in striated muscle in endotoxemia].

Under the experimental conditions of endotoxinemia, the therapeutic use of an intravenous infusion of adenosine (110 micrograms x kg-1 x min-1) has been investigated in the microcirculation model of the BALB/c mouse. Injection of S. abortus-equi endotoxin (2 mg x kg-1 body wt.

Evaluation of murine liver transmission electron micrographs by an innovative object-based quantitative image analysis system (Cellenger).

Background: Transmission electron micrographs are widely used to demonstrate tissue damage. However, the results are qualitative and dependent on the experience of the investigator. Recently, a new multiscale object-based quantitative image analyzing systems (Cellenger) has been introduced to study highly textured black-and-white images.

Heat-shock preconditioning protects fatty livers in genetically obese Zucker rats from microvascular perfusion failure after ischemia reperfusion.

Reduced tolerance of steatotic livers to ischemic injury is considered to correlate with impaired microcirculation. The aim of this study was to investigate the impact of heat-shock preconditioning (HSPC) on microcirculatory failure after ischemia/reperfusion (I/R) in steatotic livers by means of intra-vital fluorescence microscopy. Obese Zucker rats were used.

Microcirculatory failure after rat liver transplantation is related to Kupffer cell-derived oxidant stress but not involved in early graft dysfunction.

Background: Microcirculatory failure, activation of Kupffer cells (KC), and the formation of reactive oxygen species (ROS) are considered pivotal mechanisms of reperfusion injury after orthotopic liver transplantation. However, the sequence of these events and their impact on early graft function remain controversial. We therefore investigated whether KC induce microcirculatory disturbances through ROS release and whether microcirculatory failure contributes to early graft function after liver transplantation.

The influence of organ temperature on hepatic ischemia-reperfusion injury: a systematic analysis.

Background: Although hepatic ischemia-reperfusion (I/R) injury can be reduced by cooling of the ischemic organ, a systematic in vivo analysis of the influence of organ temperature in I/R injury is missing. The aim of this study was to systematically investigate the impact of defined temperatures of the ischemic liver tissue on microvascular I/R injury.

Methods: Ischemia of the left liver lobe was induced in C57BL/6 mice for 90 min.

Ischemia at 4 degrees C: a novel mouse model to investigate the effect of hypothermia on postischemic hepatic microcirculatory injury.

Hypothermia of the ischemic organ at 4 degrees C protects hepatic microcirculation from ischemia-reperfusion (IR) injury. The effect of hypothermia during ischemia was investigated in animal models using liver transplantation and storage of the harvested organ in cold preservation solutions. No investigation of the isolated influence of hypothermia at 4 degrees C of the ischemic organ on hepatic IR injury exists, due to the lack of an appropriate animal model.

Role of hypotension in brain-death associated impairment of liver microcirculation and viability.

Hypotension in brain-dead organ donors is considered a determinant factor of graft viability. The aim of this study was to elucidate the role of hypotension in brain-death associated impairment of hepatic microcirculation and function. Male Sprague-Dawley rats with an intracranial balloon were used.

Effect of lung water content, manipulated by intratracheal furosemide, surfactant, or a mixture of both, on compliance and viscoelastic tissue forces in lung-lavaged newborn piglets.

Objective: To study the impact of lung water content and its reduction by a topically applied diuretic on respiratory and lung tissue mechanics in comparison with surfactant administration in surfactant-deficient newborn piglets with lavage-induced lung injury.

Design: Controlled, randomized study.

Setting: Animal research facility.

Fibrinogen deposition at the postischemic vessel wall promotes platelet adhesion during ischemia-reperfusion in vivo.

Following ischemia-reperfusion (I/R), platelet adhesion is thought to represent the initial event leading to remodeling and reocclusion of the vasculature. The mechanisms underlying platelet adhesion to the endothelium have not been completely established. Endothelial cells rendered ischemic acquire a procoagulant phenotype, characterized by fibrinogen accumulation.

Effects of the phlebotropic drug Daflon 500 mg on postischemic reperfusion injury in striated skin muscle: a histomorphologic study in the hamster.

The objective of this study was to investigate the effects of the purified, micronized, flavonoid fraction Daflon 500 mg (S 5682, 90% diosmin and 10% hesperidin) on tissue damage and leukocyte emigration in striated skin muscle after ischemia-reperfusion, as assessed by histomorphometric analysis. The experimental model used was the transparent dorsal skin fold chamber in the awake Syrian golden hamster. Sixty-four animals were randomly allotted to two treatment groups and time points of investigation.

Effects of the phlebotropic drug Daflon 500 mg on postischemic microvascular disturbances in striated skin muscle: an intravital microscopic study in the hamster.

The objective of this study was to investigate the effects of the micronized purified flavonoid fraction Daflon 500 mg (90% diosmin and 10% hesperidin) on I/R-induced microvascular leukocyte-endothelium interaction and leakage of the high molecular weight plasma tracer FITC-dextran (relative molecular mass, 150 kd) as assessed in the striated skin muscle of the dorsal skin fold chamber model in the hamster. Intravital fluorescence microscopy was used for analysis of microvascular perfusion, leukocyte-endothelium interaction, and macromolecular leakage of FITC-dextran 150 kd in the striated skin muscle of the hamster. A tourniquet ischemia of 4 hours' duration was induced followed by reperfusion.

Time-dependent efficacy of initial reperfusion with 2,3 butanedione monoxime (BDM) on release of cytosolic enzymes and ultrastructural damage in isolated hearts.

Background: Reperfusion injury after cardioplegia may not be sufficiently addressed by conventional cardioplegic techniques in open heart surgery. 2,3-butanedione monoxime (BDM) has the potential to reduce myocardial reperfusion injury by uncoupling myocyte contraction from the intracellular calcium concentration, thus reducing reperfusion contracture. The aim of this study was to investigate the effects of different application periods of BDM during initial reperfusion on myocardial tissue injury after cardioplegia.

Changes in hepatic microcirculation and histomorphology in brain-dead organ donors: an experimental study in rats.

Objective: To assess the effect of brain death on hormonal homeostasis, hepatic microcirculation, and histomorphology in organ donors.

Design: Prospective randomised experimental study.

Setting: Institute for Surgical Research, Germany.

Optimizing the oxygen balance during initial reperfusion with 2,3-butanedione monoxime attenuates cardiac reperfusion injury.

The effect of 20 mmol/L butanedione monoxime on myocardial ischemia/reperfusion damage was studied in isolated guinea pig hearts. Three groups of hearts (n = 8) were perfused in the Langendorff mode and cardioplegic arrest was induced with St. Thomas Hospital II solution (STS) at 37 degrees C for 50 min.

The nitric oxide donor sodium nitroprusside protects against hepatic microcirculatory dysfunction in early endotoxaemia.

Objective: Endotoxin rapidly inhibits the activity of the constitutive endothelial nitric oxide synthase (ecNOS); this precedes the production of NO from inducible NOS (iNOS). This leaves a period in early endotoxaemia with a supposed scarcity of NO. The present study was conducted to examine the effects of external supplementation of NO on liver microcirculation and function.

Resuscitation with hypertonic saline dextran reduces endothelial cell swelling and improves hepatic microvascular perfusion and function after hemorrhagic shock.

Background: Hemorrhagic shock severely compromises hepatic microcirculation and function with tendency to promote hepatic insufficiency and multiple organ failure.

Material And Methods: The aim of the study was to evaluate the effects of small volume resuscitation on liver microcirculation (intravital fluorescence microscopy and electron microscopy) and function (arterial ketone body ratio (AKBR) and bile flow), in a rat model of traumatic-hemorrhagic shock. One hour after hemorrhage (MAP 40 mm Hg) the rats were resuscitated with HSD (7.

Prevention of initial perfusion failure during xenogeneic ex vivo liver perfusion by selectin inhibition.

Background: Endothelial cell activation triggered by xenoreactive antibodies and complement products is the main feature of discordant xenograft rejection. The contribution of early cell-mediated mechanisms to this rejection process is poorly understood, and the function of adhesion molecules in xenogeneic cell interactions in vivo is unclear. The aim of the study was to investigate the role of selectins in mediating cell-dependent initial perfusion failure and functional restrictions in xenoperfused guinea pig (GP) livers.

Attenuation of postischemic reperfusion injury in striated skin muscle by diaspirin-cross-linked Hb.

Hemoglobin-based oxygen carriers have been suggested to enhance the formation of oxygen free radicals, especially under conditions of ischemia-reperfusion (I/R), in which activation and adhesion of leukocytes play a pivotal role for propagation of reperfusion injury. This study investigates the effects of the hemoglobin-based oxygen carrier diaspirin-cross-linked hemoglobin (DCLHb) in an I/R model of hamster striated skin muscle. The dorsal skinfold chamber model in the awake Syrian golden hamster was used for analysis of the microcirculation and local tissue PO2 in striated skin muscle utilizing the technique of intravital fluorescence microscopy and a multiwire platinum surface (Clark type) electrode.

Efficacy of myocardial initial reperfusion with 2,3 butanedione monoxime after cardioplegic arrest is time-dependent.

Objective: In a previous study, initial reperfusion of isolated hearts after cardioplegic arrest with 2,3 butanedione monoxime (BDM) for 5 min was markedly superior to warm hyperkalemic reperfusion in improving the initial oxygen balance and reducing reperfusion arrhythmias. However, left ventricular contractility was only marginally enhanced. The goal of the present study was to test, wether the efficacy of BDM reperfusion can be enhanced by prolonging the application period.

Platelet-endothelial cell interactions during ischemia/reperfusion: the role of P-selectin.

Growing evidence supports a pathophysiological role for platelets during the manifestation of postischemic reperfusion injury; in the current study, we investigated the nature and the molecular determinants of platelet-endothelial cell interactions induced by ischemia/reperfusion (I/R). Platelet-endothelium and leukocyte-endothelium interactions after 1 hour of ischemia were monitored in vivo within mouse small intestine. By intravital fluorescence microscopy, we observed that platelets, like leukocytes, roll along or firmly adhere to postischemic microvascular endothelial cells.

Impact of dextran on microvascular disturbances and tissue injury following ischemia/reperfusion in striated muscle.

The aim of this study was to evaluate the effect of dextran (Dx) 1 versus Dx 60 (molecular weights 1,000 and 60,000) on microvascular disturbances and tissue injury in striated muscle after ischemia/reperfusion (I/R). Experiments were performed using a 4 h pressure-induced ischemia model in the hamster dorsal skinfold chamber. Three groups (n=6) of animals received a continuous infusion (45 min, 3 microL/min) of either Dx 1 or Dx 60 (total dose 5 mg/kg) or saline solution beginning 15 min before reperfusion.