Biomedical subjects
I Marzi
Publications and source records attributed to I Marzi.
Influence of pentoxifylline and albifylline on liver microcirculation and leukocyte adhesion after hemorrhagic shock in the rat.
The aim of this study was to evaluate the effects of two xanthine derivates, pentoxifylline (PTX) and its more metabolically stable analogue, albifylline (HWA 138), on hepatic sinusoidal perfusion and leukocyte endothelial interactions in the liver after hemorrhagic shock. Sprague-Dawley rats (n = 8 per group) were exposed to hemorrhagic shock at 40 mm Hg for 60 minutes and subsequently resuscitated with 60% of shed blood and lactated Ringer's solution before intravital microscopy of the liver 3 hours after resuscitation. Using fluorescence markers, quantitative evaluations of red blood cell (RBC) and white blood cell (WBC) velocities and WBC endothelium interactions were performed. Animals were chosen randomly and blindly to receive either PTX or HWA 138 in a dosage of 25 mg/kg body weight 1 minute before resuscitation, or they received placebo. This was followed by a further infusion of 25 mg/kg body weight during the 3-hour resuscitation period. Although systemic parameters were comparable in all groups, both xanthine derivates enhanced the reduced velocity of RBCs and WBCs of the placebo group. Pathological values of WBC endothelium adhesion in the placebo group (adhesion index: 126.7 +/- 19.5 s/100 WBCs, mean +/- SE) was significantly reduced by PTX (64.4 +/- 10.5, p < 0.05) and HWA 138 (71.9 +/- 10.7, p < 0.05). The results indicate a significant reduction of shock-induced leukocyte adhesions to the sinusoidal endothelium in the liver. In addition, both xanthine derivates led to improved microvascular blood flow in the liver. Thus, PTX and HWA 138 reveal multiple positive effects on early shock-induced alterations in the liver, supporting earlier studies which indicated their potential application in shock therapy.
[Management of polytrauma].
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[Pathophysiology of polytrauma].
Sequential organ failure after multiple trauma emerges from a whole-body inflammatory process which develops as a complex host defense response to hypovolemic shock/resuscitation and traumatic tissue injury. Successful prevention and treatment involves exact assessment of inflicted damage and profound knowledge of the different stages of posttraumatic immune alterations. Local release of potent inflammatory mediators (cytokines, complement, arachidonic acid derivatives, reactive oxygen metabolites) primarily induces a repair process. However, massive soft tissue and bone injury, follow-up surgery, infections and blood transfusions trigger a systemic spill over of these mediators orchestrating a generalized inflammatory response (Systemic Inflammatory Response Syndrome, SIRS). Diffuse capillary leakage and microcirculatory disorder prepare cellular dysfunction. Secondary severe immune defects support septic complications which maintain an autodestructive process. Therapeutical advances depend on the analysis of local and time-dependent expression of relevant inflammatory mediators and cellular signalling systems.
[Shock room management of polytrauma].
The emergency room functions as a junction between preclinical and early clinical treatment of patients with multiple trauma and should have defined technical and room possibilities. The personal staff should continue resuscitation measures and perform clinical and technical diagnostic procedures according to trained algorithms. The recognition of life-threatening injuries, the set up of correct priorities and application of respective surgical procedures characterize a good emergency room management.
[Strategy of surgical management of polytrauma].
Operative procedures in multiple injured patients consist in the first stage in life-saving operations such as control of bleeding and cerebral decompression. Operative measures during the urgent second operative phase have to be undertaken under consideration of the development of a multiple organ failure syndrome. Early stabilization of relevant extremity fractures and thorough care of soft-tissue are of particular importance (day-1-surgery). Only second look procedures to optimize soft-tissue injuries and prevent infections may be allowed during this early intensive care period. Delayed operative procedures should only be performed after stabilization of the overall patient situation to prevent enhancement of the systemic inflammatory response. The required operative procedures of the multiple injuries have to be attributed to the respective operative phases.
[Perspectives of polytrauma management].
Despite a high standard of preclinical, clinical and rehabilitative trauma care, the number and degree of injuries will remain a social and medical challenge. Improvements of trauma care in the future may be possible in respect to social, economic, organisational, clinical and research issues. Prevention of trauma will be of major impact and improvements may be possible by preventive legislation and technical developments. Organisation of trauma care should integrate high level trauma centres early-on including a national, regional and local quality control system. The future preclinical and clinical individual care of multiple trauma patients should consider the complex pathophysiological mechanisms at all levels, while the understanding of these mechanisms is increasing continuously.
[Spiral CT of the thorax in primary diagnosis and intensive treatment of polytrauma patients].
The performance of a rapid spiral chest CT scan during primary diagnosis and intensive care leads, in a high percentage of cases, to clinically relevant diagnoses. In particular, occult ventral (tension-) pneumothoraces and lung contusions have been found in one third of polytraumatized patients both initially and during the sequential course. Additional insertion of chest tubes has been observed to be the major consequence.
Undissolved particles in UW solution cause microcirculatory disturbances after liver transplantation in the rat.
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N-acetylcysteine failed to improve early microcirculatory alterations of the rat liver after transplantation.
The application of radical scavengers reduces reperfusion injury of liver grafts despite the natural occurrence of cellular defense mechanisms enabling the cell to tolerate moderate oxidant stress without further cell damage. The glutathione peroxidase mechanism of the liver serves to reduce hydroxyl radical-induced lipid peroxidation by releasing reduced glutathione from intracellular stores. There is evidence that the application of cysteine-providing amino acids for glutathione synthesis could maintain or even increase liver glutathione. Therefore, the purpose of this study was to evaluate the effect of N-acetylcysteine (NAC) on oxidative stress-induced reperfusion injury after liver transplantation. This was done by applying intravital microscopy. Livers from female Sprague-Dawley rats weighing 220-260 g were stored for 20 h in University of Wisconsin (UW) solution and transplanted orthotopically using the cuff technique. Donors were given 150 mg/kg body weight NAC i.v. or placebo in a blind, random fashion 6 h prior to harvesting, followed by two injections of 50 mg/kg body weight, 4 and 2 h before explantation. In additional experimental groups, recipients were given a bolus of 83 mg/kg body weight NAC or placebo at the beginning of the recipient operations, 1 min prior to reperfusion, and 60 min after surgery. Ninety minutes after transplantation, intravital microscopy was applied and five liver lobules were recorded for 30 s after injection of acridine orange, a fluorescent leukocyte marker. Sinusoidal perfusion, sinusoidal width, and leukocyte adhesion, as well as reduced and oxidized glutathione, were determined in all livers.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparative effects of secretin (SEC) and cholecystokinin-octapeptide (CCK-8) on pancreatic microcirculation.
Using epifluorescent microscopy, we investigated the dynamic changes in pancreatic microcirculation in vivo after bolus administration of secretin (SEC) (0.1-10.0 micrograms/100 g body wt) and cholecystokinin-octapeptide (CCK-8) (0.005-1.2 micrograms/100 g body wt) in pentobarbital-anesthetized rats. Pancreatic capillary red cell velocity as a monitor for pancreatic capillary blood flow was measured in 1-min intervals from 2 min prior to 8 min following bolus infusion of SEC or CCK-8. Physiological concentrations of SEC did not increase pancreatic capillary blood flow. However, pharmacological SEC concentrations induced a dose-dependent increase in pancreatic capillary blood flow (to 162 +/- 19% of baseline; P < 0.05), due to an increase in blood flow velocity (to 153 +/- 18% of baseline; P < 0.05). In contrast, bolus administration of physiological CCK-8 concentrations, which have been proven to stimulate enzyme secretion, induced a transient and dose-dependent increase in pancreatic capillary blood flow (to 235 +/- 24% of baseline; P < 0.05), due to an increase in blood flow velocity (to 184 +/- 13% of baseline; P < 0.05) and capillary diameters (+0.63 +/- 0.15 micron; P < 0.05).
[Effects of desflurane on liver microcirculation in comparison with isoflurane and pentobarbital. An intravital microscopy study in the rat].
OBJECTIVE: It is well known that the volatile anaesthetics halothane, enflurane and isoflurane alter hepatic blood flow in a dose-dependent manner. However, there are only a few studies investigating the effect of the new anaesthetic desflurane on the hepatic blood flow. In particular no information is available about the influence of desflurane on liver microcirculation. Therefore, the aim of this study was to evaluate the effects of desflurane in comparison to isoflurane and pentobarbital on microcirculation of the liver in vivo using intravital fluorescence microscopy. MATERIALS: 18 female Sprague-Dawley rats were anaesthetised with pentobarbital sodium, tracheotomised and mechanically ventilated using a rodent ventilator. A midline laparotomy was performed for later intravital microscopy of the liver. At the beginning of the one-hour ventilation period the animals were assigned to one of the following groups: isoflurane 0.75 MAC, desflurane 0.75 MAC and pentobarbital group. Animals of the pentobarbital group received additionally 25 mg/kg pentobarbital intravenously. After 60 min of ventilation and continuous monitoring of the systemic circulation the hepatic microcirculation was investigated by intravital fluorscence microscopy. RESULTS: Mean arterial blood pressure decreased slightly in the isoflurane and the desflurane groups compared to the pentobarbital group. Neither isoflurane nor desflurane did affect the sinusoidal diameters or the sinusoidal blood flow compared to the pentobarbital group. CONCLUSION: Hepatic microcirculation is not affected by one-hour anaesthesia with 0.75 MAC isoflurane or desflurane in comparison to pentobarbital.
[Effect of organ preservation conditions on reperfusion after liver transplantation].
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Attenuation of shock-induced hepatic microcirculatory disturbances by the use of a starch-deferoxamine conjugate for resuscitation.
OBJECTIVE: To determine the effects of a hydroxyethyl starch-deferoxamine conjugate on hepatic microcirculation in an isobaric, anesthetized rat model of hemorrhagic shock and asanguineous resuscitation. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty-three female, inbred Lewis rats (190 to 215 g). INTERVENTIONS: After anesthesia (pentobarbital-sodium; 50 mg/kg), tracheotomy, and cannulation, animals were assigned to a hemorrhagic shock (mean arterial pressure at 40 +/- 3 mm Hg for 45 mins) or a time-matched sham protocol. Rats in the shock groups received either hydroxyethyl starch or a starch-deferoxamine conjugate for resuscitation. Liver microcirculation was assessed in vivo 60 mins after onset of volume therapy by epifluorescence microscopy. MEASUREMENTS AND MAIN RESULTS: Conventional resuscitation with the starch-vehicle failed to restore sinusoidal blood flow compared with either time-matched controls (71% of control value; p < .01) or the starch-deferoxamine-treated animals (89% of control value; p < .05 compared with starch-vehicle), although a comparable restoration of central hemodynamics was achieved with both starch preparations. Additionally, treatment with the starch-deferoxamine conjugate resulted in a significant attenuation of sinusoidal leukocyte margination (sham 72.4 +/- 11.0/mm2; starch-vehicle 194.5 +/- 19.0/mm2 [p < .01 compared with controls]; starch-deferoxamine conjugate 135.9 +/- 12.1/mm2 [p < .02 compared with sham and starch-vehicle]). CONCLUSIONS: Asanguineous resuscitation with conventional hydroxyethyl starch failed to restore hepatic microvascular blood flow, despite otherwise effective resuscitation. In contrast, the starch-deferoxamine conjugate improved volumetric blood flow and attenuated leukocyte margination in hepatic sinusoids compared with starch-vehicle, suggesting involvement of iron-dependent, oxygen-derived radicals in shock-induced hepatic microcirculatory disturbances.
Interleukin-1 receptor antagonist attenuates leukocyte-endothelial interactions in the liver after hemorrhagic shock in the rat.
OBJECTIVE: To evaluate the influence of interleukin-1 on leukocyte-endothelial cell interactions and the microcirculation in the liver after hemorrhagic shock by means of intravital microscopy using an interleukin-1 receptor antagonist (IL-1ra). DESIGN: Prospective, randomized, blinded, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized female Sprague Dawley rats weighing 200 to 230 g. INTERVENTIONS: Hypovolemic shock was induced and maintained for 1 hr (mean arterial pressure 40 mm Hg; cardiac output 50% of baseline). After adequate resuscitation and 5 hrs of reperfusion (mean arterial pressure > 100 mm Hg; cardiac output > 120% of baseline), the microcirculation in liver sinusoids was examined by intravital fluorescence microscopy. Continuous administration of IL-1ra (5 mg/kg/hr) was started at different times in a prospective, randomized, blinded fashion, either as pretreatment 5 mins before shock induction (n = 6), or as therapy at the time of resuscitation (n = 6). An additional bolus injection of 5 mg/kg of IL-1ra was given to the latter group. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, cardiac output, heart rate, and blood gases were comparable in all shock groups during the experiments. The percentage of permanently adherent leukocytes (adhesion time of > 20 secs) in the pretreated group was significantly decreased in comparison with the control group (pretreatment group 16.9 +/- 1.9% vs. control group 42.1 +/- 5.4%; p < .001 by analysis of variance; sham group 9.1 +/- 1.1%). Administration of IL-1ra at the time of resuscitation also reduced firm adhesion of leukocytes to sinusoidal endothelium (treated group 28.8 +/- 3.6%, p < .01). Temporary adhesion rates of leukocytes (adhesion time of < 20 secs) were unaffected by pretreatment or treatment with IL-1ra with respect to control values. Liver microcirculation was impaired after hemorrhagic shock but not improved by IL-1ra. CONCLUSIONS: The results show that adhesion of leukocytes to hepatic sinusoidal endothelium is at least partly regulated by interleukin-1. Adherence was attenuated by the application of IL-1ra, which might be due to diminished expression of adhesion receptors by endothelial cells or leukocytes. Even administration of IL-1ra at the time of resuscitation reduces the early inflammatory response in the liver after shock, thus offering a potentially important therapeutic approach.
A natural glycoprotein inhibitor (NIF) of CD11b/CD18 reduces leukocyte adhesion in the liver after hemorrhagic shock.
This study was designed to assess the effect of neutrophil inhibitory factor (NIF), a novel specific inhibitor of CD11b/CD18 on hepatic leukocyte trafficking by intravital microscopy 5 h after hemorrhagic shock. Anesthetized rats were instrumented for invasive hemodynamical monitoring. Hemorrhagic shock was induced for 60 min by withdrawal of arterial blood (mean arterial blood pressure = 40 mmHg). Rats were adequately resuscitated for 5 h to achieve a mean arterial blood pressure > 100 mmHg and were randomly assigned to blinded treatment with NIF or placebo control protein administered as a single intravenous bolus (10 mg/kg) at the time of resuscitation. Intrahepatic leukocyte adhesion was evaluated by in vivo fluorescence microscopy. There were no significant differences observed in hemodynamic parameters between the shock groups throughout the study, however, NIF significantly reduced firm leukocyte adhesion in liver sinusoids. The results suggest that NIF may be beneficial in the attenuation of the pathological shock-induced leukocyte adhesion.
Influence of venovenous hemofiltration on posttraumatic inflammation and hemodynamics.
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Effect of anti-tumor necrosis factor alpha on leukocyte adhesion in the liver after hemorrhagic shock: an intravital microscopic study in the rat.
Tumor necrosis factor (TNF) plays a well known role during the development of multiple organ failure, in part due to its role for the expression of adhesion molecules on endothelial cells, thereby contributing to inflammatory reactions. The purpose of this study was to investigate the effects of TNF on leukocyte-endothelial interactions in the liver as a key organ during the systemic inflammatory response syndrome. In Sprague-Dawley rats (n = 6/group) hemorrhagic shock was induced by reduction of the mean arterial blood pressure (MAP) to 40 mmHg for 45 min; resuscitation was initiated by retransfusion of shed blood (60%) and Ringer's lactate. At 1 and 5 h after resuscitation, intravital microscopy of the liver was performed after injection of acridine orange as marker of leukocytes in sham-control animals and in shock animals pretreated with anti-TNF monoclonal antibody (2 mg/kg b.w. TN3; Celltech, Slough, UK) or NaCl .9% 2 h prior to shock induction, respectively. At constant systemic hemodynamic conditions in all groups (e.g., normal MAP), sinusoidal diameters and sinusoidal blood flow were comparably decreased to approximately 75% of control values in all shock groups. Significant differences were observed particularly in respect to permanent adherent leukocytes with 31.8 +/- 4.7% in the shock/NaCl group and 20.7 +/- 2.6% (mean +/- S.E., p < .05) in the shock/TN3 group 5 h after resuscitation following hemorrhagic shock. Consistently higher adhesion rates were observed in the portal regions compared to pericentral regions of the liver lobules.(ABSTRACT TRUNCATED AT 250 WORDS)