Effect of salvianolic acid B on TNF-a induced cerebral microcirculatory changes ina micro-invasive mouse model

Purpose: To investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor a (TNF-a) induced alterations of cerebral microcirculation with a bone-abrading model. Methods: The influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 mg/kg$bw TNF-a on cerebral venular leakage of fluorescein isothiocyanate (FITC)- albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G. The therapeutical effects of SAB on TNF-a induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg$h SAB starting at 20 min before or 20 min after TNF-a administration, respectively. The expressions of CD11b/CD18 and CD62L in leukocytes were measured with flow cytometry. Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells. Results: Compared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-a intervention only caused responses of vascular hyperpermeability and leukocyte rolling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CD11b/CD18 and CD62L in leukocytes and E-selectin and ICAM-1 in endothelial cells induced by TNF-a. Conclusions: The pre- and post-applications of SAB during TNF-a stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.     

Sevoflurane Depresses Myocardial Contractility Less than Halothane during Induction of Anesthesia in Children

Background: Cardiovascular stability is an important prerequisite for any new volatile anesthetic. We compared echocardiographically derived indices of myocardial contractility during inhalation induction with sevoflurane and halothane in children.

Methods: Twenty children were randomized to receive either halothane or sevoflurane for inhalation induction of anesthesia. No preoperative medications were given. Myocardial contractility was evaluated at baseline and at sevoflurane and halothane end-tidal concentrations of 1.0 minimum alveolar concentration (MAC) and 1.5 MAC.

Results: There were no differences between groups in patient age, sex, physical status, weight, or height. Equilibration times and MAC multiples of sevoflurane and halothane were comparable. Vital signs remained stable throughout the study. Left ventricular end-systolic meridional wall stress increased with halothane but remained unchanged with sevoflurane. Systemic vascular resistance decreased from baseline to 1 MAC and 1.5 MAC with sevoflurane. Halothane depressed contractility as assessed by the stress-velocity index and stress-shortening index, whereas contractility remained within normal limits with sevoflurane. Total minute stress and normalized total mechanical energy expenditure, measures of myocardial oxygen consumption, did not change with either agent.     

Acute loss of renal function attenuates slow leukocyte rolling and transmigration by interfering with intracellular signaling

Acute loss of renal function reduces leukocyte recruitment into inflamed tissues, and we studied the molecular basis of this using intravital microscopy of cremaster muscle and an autoperfused flow chamber system after bilateral nephrectomy or sham operation in mice. Acute loss of renal function resulted in cessation of selectin-induced slow leukocyte rolling on E-selectin/intercellular adhesion molecule 1 (ICAM-1) and P-selectin/ICAM-1. It also reduced in vivo neutrophil extravasation (assessed by reflected light oblique transillumination) without affecting chemokine-induced arrest. This elimination of selectin-mediated slow leukocyte rolling was associated with a reduced phosphorylation of spleen tyrosine kinase, Akt, phospholipase C-γ2, and p38 MAPK. However, the levels of adhesion molecules located on the neutrophil surface were not altered. Leukocytes from critically ill patients with sepsis-induced acute kidney injury showed a significantly higher rolling velocity on E-selectin/ICAM-1- and P-selectin/ICAM-1-coated surfaces compared with patients with sepsis alone or healthy volunteers. Thus, an acute loss of renal function significantly impairs neutrophil rolling and transmigration, both in vivo and in vitro. These effects are due, in part, to decreased phosphorylation of selectin-dependent intracellular signaling pathways.     

活血化瘀注射液对大鼠肠系膜活体微循环作用的观察

目的：观察血活化瘀注射液（HHI-I）对大鼠肠系膜活体微循环的影响。方法：将观察到的毛细血管后静脉微循环现象记录于录象带留作分析。观察指标包括白细胞滚动数、粘附数、平均血流速度和壁切率。结果：HHI-I及丹参注射液对生理状态下的肠系膜微循环无作用,急性胰腺炎（AP）使微循环各指标明显恶化,于AP造模的同时给予HHI-I可防止微循环障碍,丹参注射液无类似作用。结论：HHI-I降低AP时的白细胞滚动及粘附数增加,能增加血流速及壁切率。     

The therapeutic effects of epidural intercellular adhesion molecule-1 monoclonal antibody in a rabbit model: involvement of the intercellular adhesion molecule-1 pathway in spinal cord ischemia

The pathophysiology of ischemia/reperfusion injury involves extravascular migration of leukocytes from the bloodstream to the site of injury. Leukocyte adhesion and intercellular adhesion molecule-1 (ICAM-1) play an important role in the recruitment of leukocytes to the site of injury. In this study, we evaluated the role of the ICAM-1 in spinal cord ischemia and the therapeutic effects of epidural ICAM-1 monoclonal antibody (Mab). The descending aorta was occluded below the renal artery with an aneurysm clip in rabbits anesthetized with halothane. The following variables were evaluated, in addition to ICAM-1 expression in the lumbar spinal cord, in animals receiving saline or ICAM-1 Mab via the epidural route: (1) leukocyte recruitment in the lumen of capillary vessels of the lumbar spinal cord (L6-7) at 8 h after 30 min of aortic occlusion and (2) neurological evaluation at 20 h after aortic occlusion of 10, 15, 17.5, 20, or 25 min. Paraplegia was graded with the following scale: Grade 0, no deficit; Grade 1, partial deficit; and Grade 2, complete paraplegia. Spinal cord ischemia increased the expression of ICAM-1 in the endothelium of spinal cord capillaries and led to capillary leukocyte recruitment and extravascular migration into the lumbar spinal cord parenchyma, which was ablated with epidural ICAM-1 Mab. Epidural ICAM-1 Mab reduced neurological deficits and offered neuroprotection. These findings demonstrate the involvement of the ICAM-1 pathway in spinal cord ischemia and the neuroprotective effects of epidural ICAM-1 Mab. Strategies to ameliorate spinal cord ischemia may entail the administration of leukocyte antiadhesion molecules into the neuraxial space.     

Effects of cardiopulmonary bypass on leukocyte and endothelial adhesion molecules

During the inflammatory response, triggered by cardiopulmonary bypass, interaction between activated leukocytes, platelets, and endothelial cells is mediated through the expression of three main groups of adhesion molecules: the selectins, the integrins, and the immunoglobulin superfamily. The selectins, which mediate the initial rolling of the leukocyte on the endothelium, are divided in three subgroups: L-selectin is expressed on all three leukocyte types, P-selectin is expressed on platelets and endothelial cells, and E-selectin is only expressed on endothelial cells. Integrins can be found on most cell types, consist of an and a β subunit and mediate firm adhesion of the leukocyte and migration into the tissues. They are classified into subgroups according to the type of their β subunit. Immunoglobulins such as ICAM-1 and VCAM-1 are expressed mainly on endothelium and act as ligands for certain integrins. This review article summarizes the existing, and rapidly expanding, literature concerning the effects of cardiopulmonary bypass on the expression of leukocyte and endothelial adhesion molecules. Deeper understanding of the behavior and the role of adhesion molecules during cardiopulmonary bypass may facilitate effective intervention in the inflammatory response process and suppression of its adverse effects.     

Effects of Intraoperative Blood Salvage on Leukocyte Recruitment to the Endothelium

Background: The contamination of salvaged wound blood with activated leukocytes has been suspected to play a role in leukocyte-mediated tissue injury by increased adhesion to the endothelium. To verify this hypothesis, the authors performed a clinical study to examine the effects of blood salvage on leukocyte-endothelial interactions.

Methods: Expression of L-selectin, CD18, and CD11b and leukocyte adhesion to activated endothelium from human umbilical veins were measured in 25 patients undergoing major orthopedic surgery. Adhesion of fluorescently labeled leukocytes was examined in a flow chamber at shear rates of 50-1,600 s-1. Comparisons were made between samples from venous blood and from processed salvaged wound blood (SWB).

Results: At 30% hematocrit, SWB contained 2,162 +/- 147 leukocytes/[mu]l. In comparison with venous blood, CD11b was up-regulated in SWB 1.3- to 3.6-fold on monocytes and neutrophils, whereas L-selectin and CD18 decreased on monocytes by 53% and 15%, respectively (P < 0.05). Despite up-regulation of CD11b, firm adhesion was significantly reduced by 74-76% in SWB. Rolling fractions and rolling velocities were significantly higher in SWB, and their relation to shear rate was markedly altered (P < 0.01). In addition, adherent leukocytes from SWB were significantly less resistant to increments of shear rate than leukocytes from venous blood (P < 0.01).     

Early expression of adhesion molecules after lung transplantation: evidence for a role of aggregated P-selectin-positive platelets in human primary graft failure.

BACKGROUND: Primary graft failure (PGF) secondary to ischemia-reperfusion injury is the main cause of death in the first month after lung transplantation. The aim of this study was to identify early cellular and immunologic events associated with PGF in human lung transplants. METHODS: Induction of P-selectin, E-selectin and intercellular adhesion molecule-1 (ICAM-1) and evaluation of leukocytes and platelets accumulation were investigated in 18 post-reperfusion surgical specimens of lung allografts by an immunohistochemical technique. RESULTS: Selectins were restricted to the venular plexus after reperfusion as in the normal lung, whereas ICAM-1 was induced in all cases on alveolar capillaries. Numerous polymorphonuclear cells (18 of 18 cases) and aggregated platelets (7 of 18 cases) were identified along the venular plexus after reperfusion. Compared with the other patients, those with aggregated P-selectin-positive platelets were characterized by a longer duration of mechanical ventilation (p < 0.01), a lower PaO2/FiO2 ratio (p < 0.01) and the presence of radiologic edema (p < 0.05) within the first 3 post-operative days. CONCLUSIONS: We showed in the reperfused lung a distinct expression of adhesion molecules on venous and capillary pulmonary endothelia that may influence the role of leukocytes and platelets during the early course of transplantation. Furthermore, the knowledge of an association between the presence of P-selectin-positive platelet aggregates and PGF criteria might have implications for graft management and therapeutic strategies.     

Halothane, Isoflurane, and Sevoflurane Reduce Postischemic Adhesion of Neutrophils in the Coronary System

Background: Polymorphonuclear neutrophils (PMNs) contribute to postischemic reperfusion damage in many organs and tissues, a prerequisite being adhesion of PMNs to vascular endothelial cells. Because adhesion processes involve orderly interactions of membrane proteins, it appeared possible that "membrane effects" of volatile anesthetics could interfere. We investigated the effects of halothane, isoflurane, and sevoflurane on postischemic adhesion of human PMNs in the intact coronary system of isolated perfused guinea pig hearts.

Methods: The hearts (n = 7-10 per group) were perfused in the "Langendorff" mode under conditions of constant flow (5 ml/min) using modified Krebs-Henseleit buffer equilibrated with 94.4% oxygen and 5.6% carbon dioxide. Global myocardial ischemia was induced by interrupting perfusion for 15 min. In the second minute of reperfusion (5 ml/min), a bolus dose of 6 x 105 PMNs was injected into the coronary system. The number of cells reemerging in the coronary effluent was expressed as a percentage of the total number of applied PMNs. Halothane, isoflurane, and sevoflurane, each at 1 and 2 minimal alveolar concentration (MAC), were vaporized in the gas mixture and applied from 14 min before ischemia until the end of the experiment.

Results: Under nonischemic conditions, 24.7 +/- 1.3% of the injected neutrophils did not reemerge from the perfused coronary system. Subjecting the hearts to global ischemia augmented retention (36.4 +/- 2.8%, P <.05). Application of halothane reduced adhesion of neutrophils to 22.6 +/- 2.1% and 24.2 +/- 1.8% at 1 and 2 MAC, respectively (P < .05). Exposure to 1 and 2 MAC isoflurane was similarly effective, whereas basal adhesion was not significantly influenced. Sevoflurane-treated hearts (1 and 2 MAC) also showed decreased adhesion of PMNs (23 +/- 2.3% and 24.8 +/- 1.8%, respectively; P < .05) and an identical reduction resulted when sevoflurane (1 MAC) was applied only with the onset of reperfusion.     

Inhibition of neutrophil activation by volatile anesthetics decreases adhesion to cultured human endothelial cells.

BACKGROUND: Polymorphonuclear leukocytes (neutrophils, PMNs) have been shown to mediate vascular and tissue injury, leading to so-called systemic inflammatory response syndrome. The authors evaluated the effect of volatile anesthetics on neutrophil adhesion to human endothelial cells, focusing on whether the inhibitory effect observed is linked to an alteration in the function of endothelial cells or neutrophils. METHODS: The adhesion of human PMNs was quantified using cultured human umbilical vein endothelial cells (HUVECs). The increase in the number of adhering PMNs was assessed when HUVECs (with 1 mM hydrogen peroxide), PMNs (with 10 nM N-formyl-methionyl-leucyl-phenylalanine), or both were prestimulated. To determine the influence of volatile anesthetics on the adhesion of PMNs, the experiments were performed in the absence or presence of 0.5, 1, and 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane, whereby HUVECs, PMNs, or both were pretreated with gas. RESULTS: Activation of HUVECs with hydrogen peroxide or stimulation of PMNs with N-formyl-methionyl-leucyl-phenylalanine resulted in a 2.5-fold increase in PMN adhesion. Preincubation of PMNs, separately, with halothane, isoflurane, or sevoflurane, respectively, abolished enhanced neutrophil adhesion to hydrogen peroxide-activated HUVECs and adhesion of PMNs prestimulated with N-formyl-methionyl-leucyl-phenylalanine to unstimulated HUVECs (maximal effect at 1 minimum alveolar concentration). No decrease in adhesion was detected when only HUVECs were pretreated with volatile anesthetics. Additional exposure of HUVECs and PMNs to volatile anesthetics had no inhibitory effect on adhesion greater than that seen when only PMNs were treated. Appropriately, the volatile anesthetics abolished the upward regulation of the adhesion molecule CD11b on PMNs (as evaluated at 1 minimum alveolar concentration each), whereas 1 minimum alveolar concentration halothane failed to affect the expression of P-selectin, an adhesion molecule on endothelial cells. CONCLUSIONS: This study indicates that halothane, isoflurane, and sevoflurane inhibit neutrophil adhesion to human endothelial cells at concentrations relevant to anesthesia in a static system. The effects appear to be mediated by inhibition of PMN activation; that is, by attenuating the upward regulation of neutrophil CD11b.     

异氟醚、七氟醚吸入麻醉对鼠骨骼肌微循环白细胞活动的影响

目的 探讨异氟醚、七氟醚吸入麻醉对鼠骨骼肌微循环白细胞活动的影响。方法 选择SD雄性大鼠20只,随机分为两组,制备提睾肌微循环模型。吸入异氟醚、七氟醚麻醉后,分别记录吸入异氟醚、七氟醚1．5MAC3h内微循环、小动脉A1的直径和血流速度,微循环毛细血管后微静脉的白细胞滚动和粘附数量。结果 吸入异氟醚、七氟醚1．5MAC3h内HR,MAP,CVP和A1的直径和血流速度无明显改变（P＞0．05）。微循环毛细血管后微静脉的白细胞流动和粘附数量显著增加（P＜0．01）。结论 长时间吸入异氟醚、七氟醚后,可引起大鼠骨骼肌微循环毛细血管后微静脉的白细胞滚动和粘附数量显著增加。     

Hypoxia and reoxygenation do not upregulate adhesion molecules and natural killer cell adhesion on human endothelial cells in vitro

Objectives: Ischemia/reperfusion injury is characterized by endothelial cell activation leading to increased expression of adhesion molecules such as inter-cellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, endothelial- and platelet-selectin (E- and P-selectin), and to the subsequent recruitment of leukocytes. The aim of the present study was to investigate the respective effects of a proinflammatory cytokine (tumor necrosis factor alpha , TNF-), hypoxia and/or reoxygenation on adhesion molecule expression and natural killer (NK) cell adhesion in an in vitro model of I/R. Methods: Human aortic endothelial cells (HAEC) were stimulated in vitro for 8h with TNF- (1000 U/ml) and exposed to hypoxia (1% O₂), reoxygenation (21% O₂) or different combinations thereof. Cell surface expression of ICAM-1, VCAM-1 and E-/P-selectin on HAEC was analyzed by flow cytometry, and culture supernatants were tested for soluble adhesion molecules by ELISA. Rolling adhesion of NK cells on HAEC was determined using a rotating assay. Results: Untreated HAEC constitutively expressed ICAM-1 on their surface but neither expressed E-/P-selectin, VCAM-1, nor shedded soluble adhesion molecules. Exposure of HAEC to hypoxia or hypoxia and reoxygenation did not upregulate cell surface expression or shedding of adhesion molecules. In contrast, TNF- significantly upregulated cell surface expression of ICAM-1, VCAM-1, and E-/P-selectin and led to the shedding of ICAM-1 and E-selectin. Combined treatment of HAEC with TNF-, hypoxia and reoxygenation reduced E-/P-selectin surface expression and enhanced E-selectin shedding, but did not further influence ICAM-1 and VCAM-1. Soluble VCAM-1 was not detected. NK cell adhesion on HAEC increased 4-fold after TNF- stimulation, but was not affected by hypoxia or hypoxia and reoxygenation. Conclusions: Both the expression of endothelial adhesion molecules and rolling NK cell adhesion was upregulated by TNF- but not by hypoxia alone or hypoxia followed by reoxygenation supporting the view that anti-inflammatory treatment may reduce ischemia/reperfusion injury.     

Effect of halothane and isoflurane on binding of ADP- and TRAP-6- activated platelets to leukocytes in Whole blood.

BACKGROUND: Adhesion of activated platelets to neutrophils and monocytes has an important role in the regulation of inflammatory processes. This study investigates whether halothane and isoflurane affect binding of activated platelets to leukocytes in human whole blood. METHODS: Citrated whole blood was incubated for 60 min with either 1 or 2 minimum alveolar concentration (MAC) halothane or isoflurane. After stimulation with adenosine-5-diphosphate (ADP) or the thrombin receptor agonist protein TRAP-6, platelet-leukocyte adhesion and surface expression of CD62P on platelets were evaluated by flow cytometry. RESULTS: Halothane led to an inhibition of agonist-induced adhesion of activated platelets to neutrophils and monocytes. One MAC halothane reduced the formation of TRAP-6-induced platelet-monocyte conjugates. After exposure to 2 MAC halothane, agonist-induced platelet-monocyte and platelet-neutrophil adhesion were inhibited. Surface expression of CD62P on ADP- and TRAP-6-stimulated platelets were significantly reduced after 1 and 2 MAC halothane. After 2 MAC isoflurane, the authors observed an increase of the percentage of lymphocytes with bound platelets after activation with ADP. The percentage of neutrophils with bound platelets after activation with ADP or TRAP-6 was also increased in this group. Two MAC isoflurane led to an increase of the percentage of platelets expressing CD62P in the unstimulated and TRAP-6 stimulated samples, and of the amount of CD62P epitopes on the surface of platelets in the ADP-stimulated samples. CONCLUSION: This study indicates that halothane inhibits, whereas isoflurane enhances, adhesion of agonist-activated platelets to leukocytes. Interaction of both anesthetics with the expression of CD62P on platelets contribute to theses effects.     

Fundamental and distinct roles of P-selectin and LFA-1 in ischemia/reperfusion-induced leukocyte-endothelium interactions in the mouse colon

OBJECTIVE: To study the adhesive mechanisms underlying ischemia/reperfusion (I/R)-induced leukocyte-endothelium interactions in the colon. SUMMARY BACKGROUND DATA: Leukocyte recruitment is a key feature in I/R-induced tissue injury, but the mechanisms regulating leukocyte rolling and adhesion in the colon are not known. The authors recently developed a new model to study the molecular mechanisms of I/R-provoked leukocyte-endothelium interactions in the colon microcirculation using inverted intravital fluorescence microscopy. METHODS: The superior mesenteric artery was occluded for 30 minutes and leukocyte responses were analyzed after 120 minutes of reperfusion in colonic venules in mice. The adhesive mechanisms underlying I/R-induced leukocyte rolling and adhesion were investigated using monoclonal antibodies against L-, E- and P-selectin, and CD11a gene-targeted mice were used to examine the role of lymphocyte function antigen-1 (LFA-1, CD11a/CD18). RESULTS: Reperfusion provoked a clear-cut increase in leukocyte rolling and adhesion in colonic venules compared to negative controls. Both P- and E-selectin mRNA were expressed in the colon after this I/R insult. Pretreatment with an anti-P-selectin antibody reduced leukocyte rolling and adhesion by 88% and 85%, respectively, whereas antibodies against L- and E-selectin had no effect. Moreover, I/R-induced leukocyte adhesion in LFA-1-deficient mice was reduced by more than 95%. CONCLUSIONS: This study provides evidence that leukocyte rolling is exclusively and nonredundantly mediated by P-selectin and that firm adhesion is supported by LFA-1 in I/R-induced leukocyte recruitment in the colon. Taken together, both P-selectin and LFA-1 may be important targets to control pathologic inflammation in I/R-induced tissue injury in the colon.     

L-selectin and leukocyte function in skeletal muscle reperfusion injury.

HYPOTHESIS: Treatment with anti-L-selectin monoclonal antibody will reduce venular neutrophil-endothelial rolling (flux and velocity) and adhesion associated with ischemia reperfusion injury in rat skeletal muscle. DESIGN: Prospective, randomized experimental trials. SETTING: Basic science research laboratory. MATERIALS: Male Wistar rats weighing 109 +/- 5 g (mean +/- SEM). INTERVENTIONS: Gracilis pedicle muscle flaps were elevated and microcirculation was observed by intravital microscopy. Two groups were evaluated: (1) the control group, which received 4 hours of global ischemia, and (2) the experimental group, which received 4 hours of global ischemia, plus treatment with anti-L-selectin monoclonal antibody 30 minutes before reperfusion. MAIN OUTCOME MEASURES: The number of rolling and adherent leukocytes in postcapillary venules were counted in the 2 groups at baseline and at 1 through 5, 10, 15, 20, 30, 45, and 60 minutes of reperfusion. RESULTS: Treatment with the monoclonal antibody to L-selectin significantly reduced the number of rolling leukocytes (flux) at 2 through 5, 20, 30, 45, and 60 minutes of reperfusion compared with controls (P<.05). Use of the monoclonal antibody significantly reduced the number of adherent neutrophils at 5, 10, 15, 20, 30, 45, and 60 minutes of reperfusion (P<.05). There was no significant difference in leukocyte velocity. CONCLUSION: L-Selectin plays a significant role in leukocyte rolling and adherence to venular endothelium in rat skeletal muscle ischemia reperfusion injury.     

In vivo visualization of hemodialysis-induced alterations in leukocyte-endothelial interactions

BACKGROUND: The aim of this study was to develop a model for hemodialysis (HD) in small animals using conventional dialysis equipment that would allow the intravital microscopic observation of leukocyte-endothelial interactions in vivo. METHODS: Cuprophan dialyzers were adapted to obtain a similar ratio of membrane area to blood volume as in clinical HD. A silicone ring was inserted into the dialyzer's inlet to limit the number of blood-perfused capillaries. Rabbits were dialyzed for one hour without a dialysate flow. RESULTS: Extracorporeal circulation with the cuprophan dialyzer resulted in a transient leukopenia and complement activation. At the nadir of leukopenia, leukocytes that rolled along the venular wall were scarcely observed, whereas rolling was abundant (54 +/- 9 per min) prior to extracorporeal circulation. The adhesion of leukocytes to the vascular endothelium was not induced. After 60 minutes, rolling of leukocytes was still reduced by 73 +/- 5.5%, despite the full recovery of circulating leukocyte counts. Extracorporeal circulation without a dialyzer also tended to reduce leukocyte rolling, although systemic leukocyte counts were not affected. CONCLUSIONS: The use of adapted conventional cuprophan hemodialyzers in rabbits yielded a transient leukopenia similar to that in clinical HD. Using intravital microscopy, we demonstrated impairment of leukocyte-endothelial interactions. In addition, our data indicate that tissues, in which leukocytes can roll and adhere, are not automatically sites of leukocyte sequestration during HD-induced leukopenia.     

Effects of intraoperative blood salvage on leukocyte recruitment to the endothelium

BACKGROUND: The contamination of salvaged wound blood with activated leukocytes has been suspected to play a role in leukocyte-mediated tissue injury by increased adhesion to the endothelium. To verify this hypothesis, the authors performed a clinical study to examine the effects of blood salvage on leukocyte-endothelial interactions. METHODS: Expression of L-selectin, CD18, and CD11b and leukocyte adhesion to activated endothelium from human umbilical veins were measured in 25 patients undergoing major orthopedic surgery. Adhesion of fluorescently labeled leukocytes was examined in a flow chamber at shear rates of 50-1,600 s. Comparisons were made between samples from venous blood and from processed salvaged wound blood (SWB). RESULTS: At 30% hematocrit, SWB contained 2,162 +/- 147 leukocytes/microl. In comparison with venous blood, CD11b was up-regulated in SWB 1.3- to 3.6-fold on monocytes and neutrophils, whereas L-selectin and CD18 decreased on monocytes by 53% and 15%, respectively (P < 0.05). Despite up-regulation of CD11b, firm adhesion was significantly reduced by 74-76% in SWB. Rolling fractions and rolling velocities were significantly higher in SWB, and their relation to shear rate was markedly altered (P < 0.01). In addition, adherent leukocytes from SWB were significantly less resistant to increments of shear rate than leukocytes from venous blood (P < 0.01). CONCLUSIONS: Despite up-regulated CD11b, integrin-mediated adhesion is markedly impaired in salvaged blood. Therefore, the effect of blood salvage cannot be predicted from cell surface expression but rather from functional assays. The former hypothesis, that leukocytes from SWB aggravate leukocyte-mediated tissue injury by increased adhesion, may not be as great a concern as previously suggested.     

Sevoflurane decreases bispectral index values more than does halothane at equal MAC multiples

At the minimum alveolar concentration (MAC) of inhaled anesthetics, 50% of subjects move in response to noxious stimulation. Similarly, at MAC-awake, 50% of subjects respond appropriately to command. The bispectral index (BIS) nominally measures the effect of anesthetics on wakefulness or consciousness. We postulated that the use of halothane with a larger MAC-awake/MAC ratio than sevoflurane would produce higher BIS values at comparable levels of MAC. We studied 33 unpremedicated patients anesthetized by inhalation, 18 with sevoflurane and 15 with halothane. We measured BIS before and during anesthesia at 1 MAC, both before and after tracheal intubation facilitated by fentanyl and rocuronium and then at 1.5 MAC. BIS measurements were made after meeting steady-state conditions. No surgery was performed during this study. BIS values in awake patients did not differ between the sevoflurane and halothane groups (96 +/- 2 and 96 +/- 2, mean +/- sd, respectively). At 1 MAC without and with neuromuscular blockade and at 1.5 MAC, BIS values for patients anesthetized with halothane (54 +/- 7, 56 +/- 7, and 49 +/- 7, respectively) exceeded those for patients anesthetized with sevoflurane (34 +/- 6, 34 +/- 6, and 29 +/- 5, respectively) (P < 0.0001). This finding adds to other evidence indicating that BIS is drug specific.     

Isoflurane pretreatment supports hemodynamics and leukocyte rolling velocities in rat mesentery during lipopolysaccharide-induced inflammation

We hypothesized that the protective effects of isoflurane (ISO) pretreatment on the vasculature may be attributed, in part, to altered leukocyte-endothelial interactions. Rats were anesthetized with pentobarbital and then randomized into four groups: control, ISO-control (pretreatment with 30 min of 1.4% ISO), lipopolysaccharide (LPS; 10 mg/kg IV), and ISO-LPS (ISO pretreatment and then LPS). The mesentery was prepared for intravital videomicroscopy. Mean arterial blood pressure (MAP), along with microcirculatory variables that included postcapillary venular and arteriolar blood flow velocity and leukocyte dynamics (number of rolling and adherent leukocytes and individual rolling leukocyte velocities), were measured hourly (baseline and at 0-4 h). In LPS rats, ISO pretreatment significantly (P < 0.05) attenuated the decrease in MAP at 2 and 4 h after LPS and increased leukocyte rolling velocities after 2-4 h. Four hours after LPS, leukocyte rolling velocities were >200% more rapid (63.7 +/- 27.6 microm/s versus 19.8 +/- 6.4 micro m/s) in ISO-LPS versus LPS rats. In control rats, ISO pretreatment had no effect on MAP or leukocyte rolling velocities but increased the number of rolling leukocytes. ISO pretreatment had no effect on arteriolar and postcapillary venular blood flow velocity in LPS rats or leukocyte adherence in LPS or control rats. In conclusion, ISO pretreatment supported hemodynamics and increased leukocyte rolling velocities but did not alter the number of rolling or adherent leukocytes in the mesenteric microcirculation during LPS-induced inflammation. IMPLICATIONS: Isoflurane pretreatment supported hemodynamics and increased leukocyte rolling velocities in the mesenteric microcirculation during lipopolysaccharide-induced inflammation. Faster rolling velocities may reduce the incidence of inflammation by decreasing leukocyte-endothelial interactions and cellular injury.     

Cardiac rhythm and left ventricular function of infants at 1 MAC sevoflurane and halothane

BACKGROUND: The implementation of sevoflurane in pediatric anesthesia practice led to a decrease in the incidence of cardiac arrest previously reported with halothane. Nevertheless, the effects of sevoflurane on cardiac rhythm and function have not been systematically investigated in infants. Thus, we compared cardiac rhythm and left ventricular function at 1 MAC sevoflurane and halothane anesthesia and investigated the potential benefit effect of atropine. METHODS: Twenty infants ASA physical status I or II were randomly assigned to have anesthesia induced with either sevoflurane (up to 5%) or halothane (up to 1.5%). After insertion of an i.v. line, anesthesia was maintained at 1 MAC sevoflurane (group S) or 1 MAC halothane (group H) with infants breathing spontaneously in 100% oxygen. Cardiac output and contractility were measured by transthoracic echocardiography. Three sets of hemodynamic parameters were averaged prior to and after administration of 20 microg x kg(-1) of i.v. atropine. RESULTS: Infants breathing spontaneously 1 MAC halothane or 1 MAC sevoflurane were found to have comparable hemodynamic parameters. After atropine administration, heart rate and cardiac index (CI) increased significantly in both groups (19.6 +/- 7.6% in group H and 21.3 +/- 13.1% in group S, 18.6 +/- 8.8% in group H and 17.7 +/- 12% in group S respectively). Moreover, atropine induced an increase in left ventricular shortening fraction with no difference between groups. In contrast, only infants in group S presented a significant increase in ejection fraction. CONCLUSIONS: Indices of left ventricular function were comparable between groups with no clinically significant change following atropine administration. The present study confirms the favorable hemodynamic profile of sevoflurane in infants breathing spontaneously at 1 MAC concentration.