Effects of erythrocyte flexibility on microvascular perfusion and oxygenation during acute anemia

2007 ◽  
Vol 293 (2) ◽  
pp. H1206-H1215 ◽  
Author(s):  
Pedro Cabrales
Keyword(s):  
Exchange Transfusion ◽  
Capillary Density ◽  
Microvascular Perfusion ◽  
Capillary Perfusion ◽  
Noninvasive Methods ◽  
Isovolemic Hemodilution ◽  
Rbc Membrane ◽  
Arterial Blood ◽  
Glutaraldehyde Solution ◽  
Fresh Rbcs

Responses to exchange transfusion using red blood cells (RBCs) with normal and reduced flexibility were studied in the hamster window chamber model during acute moderate isovolemic hemodilution to determine the role of RBC membrane stiffness in microvascular perfusion and tissue oxygenation. Erythrocyte stiffness was increased by 30-min incubation in 0.02% glutaraldehyde solution, and unreacted glutaraldehyde was completely removed. Filtration pressure through 5-μm pore size filters was used to quantify stiffness of the RBCs. Anemic conditions were induced by two isovolemic hemodilution steps using 6% 70-kDa dextran to a hematocrit (Hct) of 18% (moderate hemodilution). The protocol continued with an exchange transfusion to reduce native RBCs to 75% of baseline (11% Hct) with either fresh RBCs (RBC group) or reduced-flexibility RBCs (GRBC group) suspended in 5% albumin at 18% Hct; a plasma expander (6% 70-kDa dextran; Dex70 group) was used as control. Systemic parameters, microvascular perfusion, capillary perfusion [functional capillary density (FCD)], and oxygen levels across the microvascular network were measured by noninvasive methods. RBC deformability for GRBCs was significantly decreased compared with RBCs and moderate hemodilution conditions. The GRBC group had a greater mean arterial blood pressure (MAP) than the RBC and Dex70 groups. FCD was substantially higher for RBC (0.81 ± 0.07 of baseline) vs. GRBC (0.32 ± 0.10 of baseline) and Dex70 (0.38 ± 0.10 of baseline) groups. Microvascular tissue Po2 was significantly lower for Dex70 and GRBC vs. RBC groups and the moderate hemodilution condition. Results were attributed to decreased oxygen uploading in the lungs and obstruction of tissue capillaries by rigidified RBCs, indicating that the effects impairing RBC flexibility are magnified at the microvascular level, where perfusion and oxygenation may define transfusion outcome.

Dexmedetomidine Attenuates the Microcirculatory Derangements Evoked by Experimental Sepsis

2015 ◽  
Vol 122 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Marcos L. Miranda ◽  
Michelle M. Balarini ◽  
Eliete Bouskela
Keyword(s):  
Blood Gases ◽  
Capillary Density ◽  
Sepsis Syndrome ◽  
In Vivo Studies ◽  
Experimental Sepsis ◽  
Leukocyte Rolling ◽  
Capillary Perfusion ◽  
Arterial Blood ◽  
Baseline Values

Abstract Background: Dexmedetomidine, an α-2 adrenergic receptor agonist, has already been used in septic patients although few studies have examined its effects on microcirculatory dysfunction, which may play an important role in perpetuating sepsis syndrome. Therefore, the authors have designed a controlled experimental study to characterize the microcirculatory effects of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microcirculation. Methods: After skinfold chamber implantation, 49 golden Syrian hamsters were randomly allocated in five groups: (1) control animals; (2) nonendotoxemic animals treated with saline; (3) nonendotoxemic animals treated with dexmedetomidine (5.0 μg kg−1 h−1); (4) endotoxemic (lipopolysaccharide 1.0 mg/kg) animals treated with saline; and (5) endotoxemic animals treated with dexmedetomidine. Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Mean arterial blood pressure, heart rate, arterial blood gases, and lactate concentrations were also documented. Results: Lipopolysaccharide administration increased leukocyte rolling and adhesion and decreased capillary perfusion. Dexmedetomidine significantly attenuated these responses: compared with endotoxemic animals treated with saline, those treated with dexmedetomidine had less leukocyte rolling (11.8 ± 7.2% vs. 24.3 ± 15.0%; P < 0.05) and adhesion (237 ± 185 vs. 510 ± 363; P < 0.05) and greater functional capillary density (57.4 ± 11.2% of baseline values vs. 45.9 ± 11.2%; P < 0.05) and erythrocyte velocity (68.7 ± 17.6% of baseline values vs. 54.4 ± 14.8%; P < 0.05) at the end of the experiment. Conclusions: Dexmedetomidine decreased lipopolysaccharide-induced leukocyte–endothelial interactions in the hamster skinfold chamber microcirculation. This was accompanied by a significant attenuation of capillary perfusion deficits, suggesting that dexmedetomidine yields beneficial effects on endotoxemic animals’ microcirculation.

Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions

2006 ◽  
Vol 291 (5) ◽  
pp. H2445-H2452 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai
Keyword(s):  
Flow Distribution ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Arterial Blood ◽  
Chamber Model ◽  
Kidney Liver ◽  
Window Chamber

The hamster window chamber model was used to study systemic and microvascular hemodynamic responses to extreme hemodilution with low- and high-viscosity plasma expanders (LVPE and HVPE, respectively) to determine whether plasma viscosity is a factor in homeostasis during extreme anemic conditions. Moderated hemodilution was induced by two isovolemic steps performed with 6% 70-kDa dextran until systemic hematocrit (Hct) was reduced to 18% ( level 2). In a third isovolemic step, hemodilution with LVPE (6% 70-kDa dextran, 2.8 cP) or HVPE (6% 500-kDa dextran, 5.9 cP) reduced Hct to 11%. Systemic parameters, cardiac output (CO), organ flow distribution, microhemodynamics, and functional capillary density, were measured after each exchange dilution. Fluorescent-labeled microspheres were used to measure organ (brain, heart, kidney, liver, lung, and spleen) and window chamber blood flow. Final blood and plasma viscosities after the entire protocol were 2.1 and 1.4 cP, respectively, for LVPE and 2.8 and 2.2 cP, respectively, for HVPE (baseline = 4.2 and 1.2 cP, respectively). HVPE significantly elevated mean arterial pressure and CO compared with LVPE but did not increase vascular resistance. Functional capillary density was significantly higher for HVPE [87% (SD 7) of baseline] than for LVPE [42% (SD 11) of baseline]. Increases in mean arterial blood pressure, CO, and shear stress-mediated factors could be responsible for maintaining organ and microvascular perfusion after exchange with HVPE compared with LVPE. Microhemodynamic data corresponded to microsphere-measured perfusion data in vital organs.

Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skinfold model

1998 ◽  
Vol 275 (6) ◽  
pp. H2170-H2180 ◽  
Author(s):  
Amy G. Tsai ◽  
Barbara Friesenecker ◽  
Michael McCarthy ◽  
Hiromi Sakai ◽  
Marcos Intaglietta
Keyword(s):  
Molecular Weight ◽  
Shear Stress ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Capillary Perfusion ◽  
Low Viscosity ◽  
Arterial Blood ◽  
Wall Shear ◽  
Stress Dependent

Effect of increasing blood viscosity during extreme hemodilution on capillary perfusion and tissue oxygenation was investigated in the awake hamster skinfold model. Two isovolemic hemodilution steps were performed with 6% Dextran 70 [molecular weight (MW) = 70,000] until systemic hematocrit (Hct) was reduced by 65%. A third step reduced Hct by 75% and was performed with the same solution [low viscosity (LV)] or a high-molecular-weight 6% Dextran 500 solution [MW = 500,000, high viscosity (HV)]. Final plasma viscosities were 1.4 and 2.2 cP (baseline of 1.2 cP). Hct was reduced to 11.2 ± 1.1% from 46.2 ± 1.5% for LV and to 11.9 ± 0.7% from 47.3 ± 2.1% for HV. HV produced a greater mean arterial blood pressure than LV. Functional capillary density (FCD) was substantially higher after HV (85 ± 12%) vs. LV (38 ± 30%) vs. baseline (100%).[Formula: see text] levels measured with Pd-porphyrin phosphorescence microscopy were not statistically changed from baseline until after the third hemodilution step. Wall shear rate (WSR) decreased in arterioles and venules after LV and only in arterioles after HV. Wall shear stress (WSR × plasma viscosity) was substantially higher after HV vs. LV. Increased mean arterial pressure and shear stress-dependent release of endothelium-derived relaxing factor are possible mechanisms that improved arteriolar and venular blood flow and FCD after HV vs. LV exchange protocols.

Microvascular perfusion deficits are not a prerequisite for mucosal injury in septic rats

1999 ◽  
Vol 276 (4) ◽  
pp. G933-G940 ◽  
Author(s):  
R. R. Nevière ◽  
M. L. Pitt-Hyde ◽  
R. D. Piper ◽  
W. J. Sibbald ◽  
R. F. Potter
Keyword(s):  
Cell Injury ◽  
Mucosal Injury ◽  
Endotoxin Tolerance ◽  
Capillary Density ◽  
Microvascular Perfusion ◽  
Myeloperoxidase Activity ◽  
Capillary Perfusion ◽  
Ileal Mucosa ◽  
Mucosal Permeability ◽  
Perfusion Deficits

Our major objective was to investigate whether injury to the mucosa of the small intestine occurred in a normotensive model of sepsis and whether such injury was associated with microvascular perfusion deficits. Using fluorescence intravital microscopy, we show direct evidence of cell injury within the mucosa (pneumonia 12.4 ± 2.6 cells/field, sham 2.2 ± 0.7 cells/field), whereas use of51Cr-labeled EDTA showed evidence of increased mucosal permeability (pneumonia 1.90 ± 0.67 ml · min−1 · 100 g−1; sham 0.24 ± 0.04 ml · min−1 · 100 g−1), 48 h following induction of pneumonia. Despite such injury the capillary density in the ileal mucosa and submucosa of pneumonic rats (1,027 ± 77 and 1,717 ± 86 mm2) was not significantly different compared with sham (998 ± 63 and 1,812 ± 101 mm2). However, a modest albeit significant decrease in capillary perfusion was measured in the muscularis layer of pneumonia (11.0 ± 1.3 mm) compared with sham (13.9 ± 0.63 mm) and appeared to be associated with leukocyte entrapment. Pretreatment using low doses of endotoxin to induce endotoxin tolerance not only increased muscularis capillary density but reduced the number of leukocytes trapped within the microvasculature, decreased myeloperoxidase activity within the ileum in pneumonic rats, and prevented mucosal injury. In conclusion, we have shown that pneumonia results in remote injury to the mucosa of the ileum and that such injury was not associated with concurrent mucosal perfusion deficits.

scholarly journals Isovolemic exchange transfusion with increasing concentrations of low oxygen affinity hemoglobin solution limits oxygen delivery due to vasoconstriction

2008 ◽  
Vol 295 (5) ◽  
pp. H2212-H2218 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai ◽  
Marcos Intaglietta
Keyword(s):  
Exchange Transfusion ◽  
Peripheral Resistance ◽  
Blood Substitutes ◽  
Microvascular Perfusion ◽  
Routine Practice ◽  
Optimal Dosage ◽  
Low Oxygen ◽  
Albumin Solution ◽  
Acid Base Balance ◽  
Capillary Perfusion

O2-carrying fluids based on hemoglobin (Hb) are in various stages of clinical trials to determine their suitability as O2-carrying plasma expanders. Polymerized Hb solutions are characterized by their vasoactivity, low O2affinity, oncotic effect, prolonged shelf life, and stability. Physiological responses to facilitated O2transport after exchange transfusion with polymerized bovine Hb (PBH) were studied in the hamster window chamber model during acute moderate anemia to determine how PBH affects microvascular perfusion and tissue oxygenation. The anemic state [29% hematocrit (Hct)] was induced by hemodilution with a plasma expander (70 kDa dextran). After hemodilution, animals were randomly assigned to different exchange transfusion groups. Study groups were based on the concentration of PBH used, namely: PBH at 13 g Hb/dl [PBH13], PBH diluted to 8 (PBH8) or 4 (PBH4) g Hb/dl in albumin solution at matching colloidal osmotic pressure (COP), and no PBH (only albumin solution) at matching COP (PBH0). Measurement of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O2levels was performed at 18% Hct. Restitution of O2-carrying capacity with PBH13 increased arterial pressure and triggered vasoconstriction, low perfusion, and high peripheral resistance. PBH4 and PBH0 exhibited lower arterial pressures compared with PBH13. Exchange transfused animals with PBH8 and PBH4 better maintained perfusion and functional capillary density than PBH13. Blood gas parameters and acid-base balance were recovered proportional to microvascular perfusion. Arterial O2tensions were improved with PBH4 and PBH8 by preventing O2precapillary release and increasing O2reserve. Further studies to establish PBH optimal dosage, efficacy, safety, and its effect on outcome are indicated before Hb-based O2-carrying blood substitutes are implemented in routine practice.

scholarly journals Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins

2010 ◽  
Vol 298 (3) ◽  
pp. H1062-H1071 ◽  
Author(s):  
Pedro Cabrales ◽  
Yipin Zhou ◽  
David R. Harris ◽  
Andre F. Palmer
Keyword(s):  
Molecular Weight ◽  
Exchange Transfusion ◽  
Tissue Oxygenation ◽  
Capillary Density ◽  
High Viscosity ◽  
Therapeutic Agents ◽  
Mechanical Stimuli ◽  
Capillary Perfusion ◽  
Ultrahigh Molecular Weight ◽  
T State

Hemoglobin (Hb)-based O2 carriers (HBOCs) constitute a class of therapeutic agents designed to correct the O2 deficit under conditions of anemia and traumatic blood loss. The O2 transport capacity of ultrahigh-molecular-weight bovine Hb polymers (PolybHb), polymerized in the tense (T) state and relaxed (R) state, were investigated in the hamster chamber window model using microvascular measurements to determine O2 delivery during extreme anemia. The anemic state was induced by hemodilution with a plasma expander (70-kDa dextran). After an initial moderate hemodilution to 18% hematocrit, animals were randomly assigned to exchange transfusion groups based on the type of PolybHb solution used (namely, T-state PolybHb and R-state PolybHb groups). Measurements of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O2 levels were performed at 11% hematocrit. Both PolybHbs were infused at 10 g/dl, and their viscosities were higher than nondiluted blood. Restitution of the O2 carrying capacity with T-state PolybHb exhibited lower arterial pressure and higher functional capillary density compared with R-state PolybHb. Central arterial O2 tensions increased significantly for R-state PolybHb compared with T-state PolybHb; conversely, microvascular O2 tensions were higher for T-state PolybHb compared with R-state PolybHb. The increased tissue Po2 attained with T-state PolybHb results from the larger amount of O2 released from the PolybHb and maintenance of macrovascular and microvascular hemodynamics compared with R-state PolybHb. These results suggest that the extreme high O2 affinity of R-state PolybHb prevented O2 bound to PolybHb from been used by the tissues. The results presented here show that T-state PolybHb, a high-viscosity O2 carrier, is a quintessential example of an appropriately engineered O2 carrying solution, which preserves vascular mechanical stimuli (shear stress) lost during anemic conditions and reinstates oxygenation, without the hypertensive or vasoconstriction responses observed in previous generations of HBOCs.

Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway

2000 ◽  
Vol 279 (1) ◽  
pp. C98-C107 ◽  
Author(s):  
J. N. Hoffmann ◽  
B. Vollmar ◽  
D. Inthorn ◽  
F. W. Schildberg ◽  
M. D. Menger
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Repeated Administration ◽  
Capillary Density ◽  
Cell Interaction ◽  
Multiple Organ ◽  
Microvascular Perfusion ◽  
Leukocyte Adherence ◽  
Capillary Perfusion ◽  
Endothelial Cell Interaction

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 PGI2, 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.

Hydroxyethyl Starch (130 kD), but Not Crystalloid Volume Support, Improves Microcirculation during Normotensive Endotoxemia

2002 ◽  
Vol 97 (2) ◽  
pp. 460-470 ◽  
Author(s):  
Johannes N. Hoffmann ◽  
Brigitte Vollmar ◽  
Matthias W. Laschke ◽  
Dietrich Inthorn ◽  
Friedrich W. Schildberg ◽  
...  
Keyword(s):  
Hydroxyethyl Starch ◽  
Striated Muscle ◽  
Isotonic Saline ◽  
Capillary Density ◽  
Cell Interaction ◽  
Capillary Perfusion ◽  
Cellular Mechanisms ◽  
Arterial Blood ◽  
Synthetic Colloid ◽  
Microcirculatory Disorders

Background Increased leukocyte-endothelial cell interaction (LE) and deterioration of capillary perfusion represent key mechanisms of septic organ dysfunction. The type of volume support, however, which may be used during septic disorders, remains controversial. Using intravital microscopy, the authors studied the effect of different regimens of clinically relevant volume support on endotoxin-induced microcirculatory disorders, including the synthetic colloid hydroxyethyl starch (HES, 130 kD) and a crystalloid regimen with isotonic saline solution (NaCl). Methods In Syrian Golden hamsters, normotensive endotoxemia was induced by intravenous application of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg). The microcirculation was analyzed in striated muscle of skinfold preparations. HES 130 kD (Voluven(R), 16 ml/kg, n = 7) or isotonic saline (NaCl, 66 ml/kg, n = 6) were infused 3 h after LPS exposure over a 1-h period (posttreatment mode). Animals receiving LPS without volume therapy served as control subjects (n = 8, control). LE, functional capillary density (FCD), and macromolecular leakage were repeatedly analyzed in the awake animals during a 24-h period using intravital fluorescence microscopy. Results HES 130 kD significantly reduced LPS-induced arteriolar and venular leukocyte adherence (P &lt; 0.05), whereas NaCl resuscitation had no effect when compared with nontreated control animals. The LPS-induced decrease in FCD and increase in macromolecular leakage were also significantly attenuated by HES 130 kD but not by NaCl. Improvement of LPS-induced microcirculatory disorders by HES was unlikely the result of macro- and microhemodynamic changes because arterial blood pressure, heart rate, and venular wall shear rate did not differ between HES- and NaCl-treated animals. Conclusions Thus, our study provides microhemodynamic and cellular mechanisms of HES 130 kD-mediated protection on microcirculation during endotoxemia, even when used in a clinically relevant posttreatment mode during normotensive conditions.

scholarly journals Tissue oxidative metabolism after extreme hemodilution with PEG-conjugated hemoglobin

2010 ◽  
Vol 109 (6) ◽  
pp. 1852-1859 ◽  
Author(s):  
Pedro Cabrales ◽  
Fantao Meng ◽  
Seetharama A. Acharya
Keyword(s):  
Energy State ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Acid Base Balance ◽  
Noninvasive Technique ◽  
Isovolemic Hemodilution ◽  
Blood Flows ◽  
Arterial Blood ◽  
Base Balance ◽  
Chamber Model

NADH-localized fluorometry was used as a noninvasive technique to monitor changes in the energy state of intact tissue (muscle and connective tissue), without anesthesia, as a function of blood plasma O2-carrying capacity in the hamster window chamber model. Acute moderate isovolemic hemodilution was induced by two isovolemic hemodilution steps: in the first step, 6% 70-kDa dextran (Dex70) was used to induce an acute anemic state (18% Hct); in the second step, exchange transfusion of polyethylene glycol (PEG) maleimide-conjugated Hb (4 g/dl, PEG-Hb) or Dex70 (6 g/dl) was used to reduce erythrocytes to 75% of baseline (11% Hct). PEG-Hb had six copies of PEG (5 kDa) conjugated to each human Hb (0.48 g PEG/g Hb) through extension arm-facilitated chemistry. Systemic parameters, microvascular perfusion, functional capillary density, intravascular and interstitial Po2, and intracellular NADH fluorescence were monitored. Mean arterial blood pressure after extreme hemodilution was statistically significantly reduced for Dex70 compared with PEG-Hb. The presence of PEG-Hb in the circulation maintained positive acid-base balance. While microvascular blood flows were not different, functional capillary density was significantly higher for PEG-Hb than Dex70. Arteriolar Po2 was higher in the presence of PEG-Hb than Dex70, but tissue and venular Po2 were not different. Cellular energy metabolism (intracellular O2) in the tissues was improved with PEG-Hb. Moderate hemodilution to 18% Hct (6.4 g Hb/dl) brings tissue O2 delivery to the verge of inadequacy. Extreme hemodilution to 11% Hct (3.7 g Hb/dl) produces tissue anoxia, and high-O2-affinity PEG-Hb (Po2 at which blood is 50% saturated with O2 = 4 Torr, 1.1 g Hb/dl) only partially decreases anaerobic metabolism without increasing tissue Po2.

Extreme hemodilution with PEG-hemoglobin vs. PEG-albumin

2005 ◽  
Vol 289 (6) ◽  
pp. H2392-H2400 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai ◽  
Robert M. Winslow ◽  
Marcos Intaglietta
Keyword(s):  
Base Excess ◽  
Microvascular Blood Flow ◽  
Oxygen Release ◽  
Capillary Perfusion ◽  
Isovolemic Hemodilution ◽  
Arterial Blood ◽  
Dextran 70 ◽  
Chamber Model ◽  
Plasma Expanders ◽  
Window Chamber

Isovolemic hemodilution to 11% systemic hematocrit was performed in the hamster window chamber model using 6% dextran 70 kDa (Dx 70) and 5% human serum albumin (HSA). Systemic and microvascular effects of these solutions were compared with polyethylene glycol (PEG)-conjugated 5% albumin (MPA) and PEG-conjugated 4.2% Hb (MP4). These studies were performed for the purpose of comparing systemic and microvascular responses of PEG vs. non-PEG plasma expanders and similar oxygen-carrying vs. noncarrying blood replacement fluids. Mean arterial blood pressure was statistically significantly reduced for all groups compared with baseline ( P < 0.05), HSA, MPA, and MP4 higher than Dx 70 ( P < 0.05). MP4 and MPA had a significantly higher cardiac index than HSA and Dx 70, in addition to a positive base excess. Microvascular blood flow and capillary perfusion were significantly higher for the PEG compounds compared with HSA and Dx 70. Intravascular Po2 for MP4 and MPA was higher in arterioles ( P < 0.05) compared with HSA and Dx 70, but there was no difference in either tissue or venular Po2 between groups. Total Hb in the MP4 group was 4.8 ± 0.4 g/dl, whereas the remaining groups had a range of 3.6–3.8 g/dl. The hemodilution results showed that PEG compounds maintained microvascular conditions with lower concentrations than conventional plasma expanders. Furthermore, microvascular oxygen delivery and extraction in the window chamber tissue were significantly higher for the PEG compounds. MP4 was significantly higher than MPA ( P < 0.05) and was not statistically different from baseline, an effect due to the additional oxygen release to the tissue by the Hb MP4.

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