Resuscitation with Recombinant Hemoglobin rHb2.0 in a Rodent Model of Hemorrhagic Shock

Background: Hemoglobin solutions combine volume effect, oxygen-carrying capacity, and vasoactive properties, the latter facilitating restoration of global hemodynamics but endangering microvascular resuscitation. Hemoglobin-evoked vasoconstriction probably is due to nitric oxide scavenging, which can be reduced by genetic modifications of the heme pocket. This study compares resuscitation with a nonhemoglobin colloid and two recombinant hemoglobin solutions with wild-type and reduced nitric oxide-scavenging capacity.

Methods: Twenty-seven awake Syrian golden hamsters fitted with dorsal skinfold chambers underwent a 30 min-hemorrhagic shock (mean arterial pressure [MAP] 30-35 mmHg) and resuscitation with shed blood volume of either 6% dextran 60 (Biophausia, Uppsala, Sweden), recombinant hemoglobin 1.1 (rHb1.1; wild-type nitric oxide-scavenging capacity; 10 g/dl), or recombinant hemoglobin 2.0 (rHb2.0; reduced nitric oxide-scavenging capacity; 10 g/dl; both Baxter Healthcare, Boulder, CO). Macrohemodynamic and laboratory parameters were assessed; microvascular parameters in the skinfold chamber were analyzed by intravital microscopy.

Results: Hemorrhagic shock reduced functional capillary density (FCD) by 70% and caused significant metabolic acidosis. Colloid resuscitation led to incomplete recovery of MAP and FCD. Infusion of rHb1.1 completely restored MAP but not FCD, with the smallest arteriolar diameters found in this group. FCD was restored best by resuscitation with rHb2.0, although MAP was lower than in rHb1.1-treated animals. Metabolic acidosis was resolved by both hemoglobin solutions, but not by dextran.     

Passive Pneumatic Stabilization Device for Assisting in Reduction of Femoral Shaft Fractures

Abstract During treatment of femoral shaft fractures, not only the actual fracture reduction but also the retention of the achieved reduction is essential. Substantial forces may apply to the bone fragments, due to multidirectional muscular contraction. Furthermore, forces from manipulation of one bone fragment may be transferred over the soft tissues onto the other fragments, thus hindering accurate fracture reduction. Once a sufficient reduction has been achieved, this position must be retained whilst definitive internal fixation is performed. Conventional methods comprise mounting patients on a traction table and applying manual distraction or employing special distraction devices, such as the AO distractor device. These approaches, however, only insufficiently stabilize both main fragments. For example, on the traction table the proximal femoral fragment can pivot around the hip joint thus complicating precise reduction. A novel pneumatic stabilization device to assist surgeons during operative procedures is described. This passive holding device “Passhold” connects to one main fragment through a minimally invasive bone interface and statically locks the fragment’s position. Thereafter, only the other main fragment is manipulated to achieve reduction. Mutual interference of the reciprocal fragment positions, due to soft-tissue force transfer during manipulation, is avoided. The authors examined the stability of the novel retention device on a test rig and proved its functionality under sterile settings using cadaver tests. It is concluded that this device largely facilitates the operative procedure in femoral shaft fractures, is sufficiently stable and ergonomically suitable for intraoperative deployment.     

Erythropoietin accelerates the recovery from extreme hemodilution: a randomized, placebo-controlled study in dogs

Six splenectomized beagles of either sex (13.8 +/- 2.2 kg) were randomly treated either with 500 U/kg recombinant human erythropoietin (rhu-EPO) (verum group, n = 3) or an equivalent volume of the vehicle (placebo group, n = 3). Both solutions were given intravenously for 3 days. At day 4 after onset of treatment, the dogs were anesthetized and subjected to isovolemic hemodilution using 6% Dextran 60 (MW 60,000) down to a hematocrit of 0.10. During the recovery period vehicle or rhu-EPO was given every other day until the hematocrit reached control values. Every day venous blood samples were withdrawn, and the hematocrit as well as the concentrations of hemoglobin and 2,3-diphosphoglycerate were determined. In addition, the platelets and reticulocytes were counted. Treatment with rhu-EPO shortened the time of hematocrit recovery from 20 (placebo) to 11 days (p less than 0.05). The reticulocyte count peaked at day 2 (verum) versus day 5 (placebo). These findings indicate a successful stimulation of red blood cell production after extreme hemodilution in animals treated with erythropoietin. Therefore, rhu-EPO may allow to optimize blood donation programs as well as preoperative hemodilution and yield both, higher amounts of autologous blood and an accelerated reversal of dilutional anemia.     

Das Lidekzem

Lidekzeme sind pathogenetisch heterogen. Ihre Behandlung ist durch die anatomischen und funktionellen Gegebenheiten der Periorbitalregion erschwert. Dies macht sie, neben ihrer h?ufigen Therapieresistenz und Rezidivneigung, zu einer gro?en diagnostischen und therapeutischen Herausforderung für Haut- und Augen?rzte.Auch ein vergleichsweise kleinfl?chiges Lidekzem kann aufgrund der belastenden Symptomatik und der hohen ?sthetischen Bedeutung dieser K?rperregion einen hohen Leidensdruck verursachen. Diese interdisziplin?re übersichtsarbeit zum Thema behandelt vor allem aktuelle pathogenetische und therapeutische Aspekte der Lidekzeme. Dr.A.Wollenberg Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universit?t München, Frauenlobstr.9-11, 80337 München, E-Mail: wollenberg@lrz.uni-muenchen.de     

In vitro effects of oxidized low density lipoprotein on CD11b/CD18 and L-selectin presentation on neutrophils and monocytes with relevance for the in vivo situation.

Oxidized LDL (oxLDL) has been identified as a potent stimulus of leukocyte adhesion to endothelium, a hallmark of early atherogenesis. A cytofluorometric study was performed to further characterize the mechanisms by which oxLDL stimulates the rapid adhesion of leukocytes to endothelium in vitro and in vivo. Incubation (30 minutes at 37 C) of whole blood (diluted with buffered saline to 1 x 10(6) leukocytes/ml) with oxLDL (0.85 mg LDL cholesterol/ml; oxidized by 7.5 mumol/L Cu2+ for 18 hours) but not native LDL stimulated the upregulation of CD11b/CD18 adhesion receptors on neutrophils (anti-leu-15 binding: 178 +/- 16% of baseline, P < 0.01, means +/- SD of n = 10 experiments) and on monocytes (169 +/- 34% of baseline, P < 0.01). This phenomenon was almost entirely inhibited by n-butanol or the vasoactive drug pentoxifylline (PTX), which also significantly reduced oxLDL-induced leukocyte adhesion to venular and arteriolar endothelium, as assessed by intravital microscopy on the dorsal skinfold chamber in hamsters (venules: 49 +/- 19 versus 120 +/- 34 cells/mm2, P < 0.05; arterioles: 9 +/- 4 versus 52 +/- 7 cells/mm2, P < 0.01) 30 minutes after intravenous injection of oxLDL (4 mg/kg body weight; means +/- SD of n = 7 hamsters per group). Butanol and PTX also significantly reduced the upregulation of CD11b/CD18 by f-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) but not by phorbol myristate acetate (PMA). Whereas fMLP and PAF stimulate leukocytes via binding to specific cell surface receptors and triggering complex signal transduction pathways, PMA bypasses these pathways and directly activates intracellular protein kinase C. By analogy, we propose that oxLDL upregulates CD11b/CD18 through its previously documented ability to stimulate the generation of second messengers. The effect of n-butanol and PTX on receptor presentation cannot be explained by changes in plasma membrane fluidity, as both agents failed to reverse the decrease in plasma membrane fluidity of neutrophils after stimulation with oxLDL, as assessed by fluorescence anisotropy measurement of the membrane marker diphenylhexatriene. Incubation of isolated neutrophils but not of whole blood with oxLDL resulted in a significant loss of L-selectin from the neutrophil surface (anti-TQ-1 binding: 40 +/- 13% of baseline, P < 0.01). A significant loss of this adhesion receptor on neutrophils and monocytes was also observed after stimulation of isolated neutrophils and whole blood with fMLP, PAF, and PMA.(ABSTRACT TRUNCATED AT 400 WORDS)