| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
* From the Departments of Anesthesiology, and
Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Address correspondence to: Dr. Marc Freitag, Department of Anaesthesiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. Phone: +49 40 42803 4409; Fax: +49 40 42803 7631; E-mail: freitag{at}uke.uni-hamburg.de
 |
Abstract |
|---|
 TOP Abstract IntroductionMethodsResultsDiscussionAPPENDIXReferences |
|---|
Methods: Twelve Foxhounds were anesthetized and then randomized to either a control group without hemodilution (Group 1) or underwent first step isovolemic hemodilution (pulmonary artery occlusion pressure constant) with Ringer’s solution (Group 2) to a hematocrit of 25% with second step infusion of HBOC-201 until a hemoglobin concentration of +0.6 g·dL–1 was reached. Tissue oxygen tensions (tpO2) were measured in the gastrocnemius muscle using a polarographic needle probe, and in the liver using a flexible polarographic electrode.
Results: While arterial oxygen content and oxygen delivery decreased with hemodilution in Group 2, global liver and muscle oxygen extraction ratio increased after hemodilution and additional application of HBOC-201. Hemodilution and application of HBOC-201 provided augmentation of the mean liver tpO2 (baseline: 48 ± 9, 20 min: 53 ± 10, 60 min: 67 ± 11*, 100 min: 68 ± 7*; *P < 0.05 vs baseline and Group 1), while oxygen tensions in Group 1 remained unchanged. Oxygen tension in the skeletal muscle increased after hemodilution and additionally after application of HBOC-201 in comparison to baseline and to the control group (P < 0.05).
Conclusion: In the present animal model, IHD with Ringer’s solution and additional application of HBOC-201 increased oxygen extraction and tpO2 in the liver and skeletal muscle, in parallel and in comparison with baseline values and a control group.
|
Introduction |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionAPPENDIXReferences |
|---|
The present prospective animal study investigated the effects of isovolemic hemodilution with Ringer’s solution and additional application of HBOC-201 on oxygen delivery and tissue oxygenation of the liver as a central organ, and of the skeletal muscle representing a peripheral organ, in comparison with a non-hemodiluted control. We tested the hypothesis that the tpO2 in skeletal muscle and the liver would increase significantly compared with baseline values, after hemodilution and additional application of HBOC-201.
|
Methods |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionAPPENDIXReferences |
|---|
Measurements and data collection
The electrocardiogram, heart rate and all hemodynamic variables were monitored continuously (Marquette, MI, USA). After surgical preparation of the right groin, an arterial catheter was placed through the femoral artery into the aorta for measurement of the mean arterial pressure (MAP) and arterial blood gas sampling. Venous access was obtained by placing an 8F introducer into the right femoral vein. A 7F pulmonary artery catheter (Oxicath®, Abbott, Germany) was inserted via the introducer for measurement of central venous pressure, mean pulmonary arterial blood pressure (MPAP), pulmonary artery occlusion pressure (PAOP) CO and temperature. CO was determined by the thermodilution method (average of three measurements) and registered by a CO computer (Oximetrix®, Abbott, Germany). Cardiac index (CI), systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were calculated.
For measurement of the oxygen content in the vena cava (CvO2 cava) the right femoral vein was used for introduction of a catheter into the inferior vena cava; this catheter was fixed directly above the junction of the liver veins and controlled under direct vision following laparotomy. A small catheter was inserted into the left popliteal vein for sampling of venous blood coming from the left M. gastrocnemius (popliteal oxygen content: CvO2 popl). An electro-magnetic flow probe (Cliniflow FK 701 D, Carolina Med. Electronics, King, NC, USA) was placed around the left popliteal artery which is the main vessel for the gastrocnemius muscle to measure the mean arterial blood flow to this muscle (Flow-popl).
After upper abdominal laparotomy and splenectomy to avoid blood pooling, a catheter was introduced in the remaining V. lienalis and advanced 5 cm into the V. portae for measurement of the oxygen content (CvO2 port) in the V. portae. Blood flow measurement (flow-port.) in the V. portae was also performed using an electromagnetic flow probe (Cliniflow FK 701 D, Carolina Med. Electronics, King, NC, USA).
Hematocrit was determined five minutes after centrifugation of arterial blood (Biofuge 17RS, Heraeus Sepatech, Harz, Germany) using a standardized scale. Hb concentrations and oximetry were analysed from arterial and venous blood samples respectively using a six-wavelength oximeter (OSM3, Radiometer, Copenhagen, Denmark). An oxygen-specific fuel cell (Lex-O2-Con, Lexington Instruments, Waltham, MA, USA) was used for measuring the arterial (A. fem.), venous (V. popl., V. portae, V. cava) and mixed-venous (A. pulm) oxygen content. Measurements were recorded and variables were calculated as out-lined in the Appendix.
Protocol (Figure 1
)
The surgical preparation and instrumentation was followed by a 20-min equilibration period. After recording all baseline variables, the animals were randomly allocated to a control group which was not hemodiluted (Group 1) or to the treatment group (Group 2) which underwent PAOP-controlled IHD to a hematocrit target value of 25% (total hemoglobin concentration of 7.4 ± 1.0 g·dL–1) with crystalloids 1:4 (Ringer’s solution). After IHD and an equilibration period of 20 min, a second measurement of all parameters was performed. After completion of the post IHD measurements, animals in Group 2 received a dose of ultrapurified, polymerized, bovine hemoglobin HBOC-201 (HemopureTM, Biopure, Cambridge, MA, USA) to ensure a plasma hemoglobin concentration of 0.6 g·dL–1 during the experiment. The amount of HBOC-201 was calculated according to the following formula: HBOC-201 (mL) = body weight x 0.6/0.13.9 This dose was chosen on the basis of data from a prior study,6 which suggested that an augmentation of at least 0.6 g·dL–1 HBOC-201 was effective in restoring tissue oxygenation to baseline values after significant reduction by profound hemodilution. HBOC-201 has a hemoglobin concentration of 13 ± 1 g·dL–1 (methemoglobin and oxyhemoglobin = 10%) and an oncotic pressure of 17 mmHg. HBOC-201 was prepared from bovine red cells by lysis, filtration, chromatography and polymerization with glutaraldehyde (65,000 < gram molecular weight < 500,000). The sterile pyrogen free solution contains < 0.5 EU mL–1 endotoxin and < 3 nM phospholipids and physiological concentrations of electrolytes.
|
The time between the respective measurements was 40 min.
Statistics
Analyses were performed using SPSS for windows 9.0 (SPSS Inc., Chicago, IL, USA). Animals were allocated to one of the two groups by a computerized randomization list. We tested the hypothesis that the 50% percentile (median) of the tpO2 in the skeletal muscle would increase significantly compared with baseline after hemodilution and additional application of HBOC-201. Based upon a recent study10 we expected baseline values of approximately 30 ± 5 mmHg, and an increase of 100% after hemodilution and additional application of HBOC-201, with an anticipated pooled standard deviation of 7.5 mmHg. We would permit a type I error of 
= 0.05, and with the error of ß = 0.2, this analysis achieves a power of 0.8, indicating a sample size requirement of at least six animals per group.
Descriptive analysis of parametric data is expressed as means and standard deviation. Ordinal data are expressed as medians. TpO2 values were tested for statistical significance using the Whitney U test or Wilcoxon rank test. Differences between the respective hemodilution steps were tested using ANOVA for repeated measurements and Student’s t test deviation. Statistical significance was assumed at P < 0.05.
|
Results |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionAPPENDIXReferences |
|---|
. Mean values of heart rate, MPAP, CI and PVR did not change over time, and were similar in both groups. The PAOP also did not change during the experiment. MAP decreased during hemodilution in Group 2 in comparison to baseline values and to Group 1. After application of HBOC-201, MAP returned to baseline values in Group 2.
|
. In both groups, temperature remained stable over time. Baseline hemoglobin concentrations and hematocrits were similar in both groups, and decreased only in Group 2 during hemodilution to values between 7.4 and 7.7 g·dL–1 with 1.0 g·dL–1 of plasma hemoglobin after administration of HBOC-201. Arterial oxygen content (CaO2 fem), CvO2 pulm and DO2 decreased after hemodilution, and remained at lower levels in Group 2 in comparison to baseline to control values. Systemic arteriovenous oxygen difference (AvDO2) only decreased in Group 2 after hemodilution, whereas VO2 remained stable. During hemodilution the global oxygen extraction ratio increased, with a further increase after application of HBOC-201 (Figure 2).
|
|
. Hemodilution decreased oxygen content both in the V. cava and the V. portae in Group 2 when compared to baseline levels and the control group. AvDO2 in the liver decreased in Group 2 after hemodilution, whereas oxygen consumption in the liver remained stable in both groups. Oxygen delivery to the liver decreased in Group 2 after hemodilution and application of HBOC-201 in comparison to the control group at the last time of measurement. Oxygen extraction ratio in the liver, (Figure 3) increased after application of HBOC-201 in Group 2.
|
|
. In accordance with the global and liver oxygen content, the popliteal oxygen content decreased during hemodilution in Group 2 (Table IV). The oxygen extraction ratio (Figure 4) in the skeletal muscle was increased during hemodilution in comparison to Group 1 and after additional application of HBOC-201 in comparison to baseline.
|
|
. In the control group, no changes in liver tpO2 were observed. Hemodilution with Ringer’s solution did not alter liver tpO2 in Group 2 whereas additional application of HBOC-201 increased the hepatic tpO2 by 45% in comparison to baseline and by 40% in comparison to the control group. The pooled histograms of oxygen tensions of the skeletal muscle are shown in Figure 6. The mean tpO2 of the skeletal muscle increased from values around 20 mmHg to 32 mmHg after hemodilution. Application of HBOC-201 was associated with an additional increase of 32% of the muscle tpO2 in comparison to post hemodilution values. The histograms of skeletal muscle tpO2 shifted to the right to higher values in Group 2, while in the control group the tpO2 did not change over time.
|
|
|
Discussion |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionAPPENDIXReferences |
|---|
The effect of maintenance or even improvement of tpO2 following hemodilution is primarily the result of increased red cell velocity in the capillaries,1 which is based mainly upon the improved rheology as a result of decreased blood viscosity and vascular tone. The basic mechanisms underlying the enhanced nutrional blood flow during IHD are caused by the improvement of blood fluidity, enhancement of shear rates, and subsequent release of endogenous nitric oxide from the vascular endothelium,11 finally resulting in vasodilation. In addition, flow motion is enhanced during hemodilution, leading to a more homogeneous delivery of oxygen to the tissues.12 In our study a significant effect could be demonstrated after first step moderate IHD with Ringer’s solution to a hematocrit of 25% in comparison to the non-hemodiluted control group with respect to tpO2 values in the skeletal muscle. An increase of tpO2 in the skeletal muscle following hemodilution has been shown before.3,5,13 However, in our experimental setting, moderate hemodilution alone was not able to increase liver tpO2. Only additional application of the cell-free HBOC-201 caused a significant increase of liver tpO2 in comparison to baseline values and the control group.
This result could make HBOC-201 an important and effective instrument to improve tissue oxygenation in the liver even in situations where rheologic therapy has reached its limitations. The precondition is, however, that HBOC-201 effectively contributes to tissue oxygenation. For the skeletal muscle this has been already shown before.6,14–18
With the polarographic needle probe higher tpO2 values were also shown in the canine skeletal muscle, during extended IHD with an ultrapurified bovine hemoglobin solution (UBPH) in comparison with hydroxyethyl starch (HES).18 Moreover, the skeletal muscle tpO2 was even higher than baseline values at a hematocrit of only 2% in presence of UPBH, which provided a plasma hemoglobin concentration of 8.2 g·dL–1 In contrast to HES, the muscular oxygen consumption was maintained under UPBH treatment, and was paralleled by an increased systemic and muscular oxygen extraction in this animal study.
Another study from our group showed similar results which were explained by facilitated O2-extraction from HBOC-201 due to its right shifted oxygen dissociation curve.6 Dogs were hemodiluted to hematocrit 10% using 6% HES and were subsequently transfused either with autologous blood (hemoglobin 9 g·dL–1) or HBOC-201 to increase the total hemoglobin concentration by 1, 2 and 3 g·dL–1 No differences were detected between groups with respect to global tissue oxygenation parameters (DO2, VO2). However, because of the superior oxygen extraction, skeletal muscle tpO2 values were significantly higher in the HBOC-201 group. After the final HBOC-201 infusion, contribution of the bovine hemoglobin to total CaO2 was 47%. The augmented oxygen extraction in presence of HBOC, because of an increased oxygen off load, seems to be a characteristic essential of modern cell-free hemoglobin solutions which provides enhanced oxygen supply at the tissue site.19
In our present study, the additional application of HBOC-201 increased the hepatic tpO2 by 45% in comparison to baseline, and by 40% in comparison to control. When these results are transferred to clinical settings, the application of HBOC-201 could be of potential benefit in surgeries where liver oxygenation is impaired, e.g., liver tumour resections or liver transplantations.
One point of criticism is the vasoconstrictive side effect associated with HBOC treatment caused by the well-known nitric oxide (NO) scavenging effect of HBOC.20,21 As a consequence of the vasoconstrictor effects, increases of the MAP and, rarely, of the PAP, and decrease of the CO were often seen in experimental and clinical studies with HBOC-201.17,22,23 It has been shown that cell-free hemoglobin molecules can be subject to uptake by vascular endothelial cells. These molecules are transferred to the media by transcytosis, where they can bind to NO, thus creating vasoconstriction, in a dose-dependent manner.21 In this study, the decreased MAP and SVR after moderate hemodilution was only restored to baseline values after application of HBOC-201. The intensity of vasoconstriction seems to be dependent upon the degree of purification of HBOC and tetrameric stabilisation,24,25 and is less pronounced with highly modified hemoglobin preparations like HBOC-201. There is also evidence that HBOC has an impact on organ blood flow and distributive oxygen transport in the microcirculation which is different from the vasoconstrictive effects on larger vessels.26 Sherman et al. have shown that systemic vasoconstriction after HBOC administration did not reduce regional blood flow in the hamster liver.27 After application of HBOC-201, the blood flow in the portal vein did not change significantly in our experiment. Data from Federspiel et al. also suggest that free hemoglobin in the plasma phase may enhance oxygen off loading to the tissues, by functionally reducing the intracapillary space between erythrocytes and endothelium, thus facilitating oxygen diffusion.28,29 A study in dogs subjected to hemorrhage showed that HBOC-201 reconstituted splanchnic perfusion and oxidative metabolism, in spite of increased SVR and consecutively decreased CO and DO2 30 Although DO2 after hemodilution in this study was decreased, the global and regional oxygen extraction in the liver and skeletal muscle increased tpO2 values after application of HBOC-201 (Figures 2
–4).
Another limitation of many studies is that measurements of tpO2 were performed only in skeletal muscle, since skeletal muscle seems to be less important than central organs.31 However, the skeletal muscle mass represents a major part of mammal and human tissues, is easily accessible, and can even be used for tpO2 measurements in patients.32 The effects of isovolemic hemodilution and additional application of HBOC-201 on the oxygenation of central organs and oxygen extraction like the liver remained unclear until now. With the results of the present study, we further underlined our hypothesis that changes in tpO2 in the skeletal muscle can approximate the changes seen in the liver during treatment with HBOC. Knudson et al. were also able to show in a prehospital model of hemorrhagic shock and resuscitation that tpO2 measured in the deltoid muscle using the Licox device reflects oxygen tension in the liver and can therefore be used as a monitor of splanchnic resuscitation.33 In addition, in a recently published editorial, the author pointed out that tpO2 is perhaps the most reliable quantitative index of tissue perfusion currently available.34
In conclusion, our data show that tissue oxygenation of the liver and skeletal muscle was increased in parallel when HBOC-201 as an oxygen delivering solution was added after moderate isovolemic hemodilution. Because of the increased oxygen off-loading capacity demonstrated by the increased oxygen extraction, HBOC-201 may help to improve liver oxygenation, even in situations where rheologic therapy has reached its limitations.
|
APPENDIX |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionAPPENDIXReferences |
|---|
The liver blood flow was assessed by the sum of the blood flow of the liver artery (approximately 1/3) and the blood flow of portal vein (approximately 2/3), which is an estimate of liver blood flow. The parameters of hepatic oxygen delivery, oxygen consumption and arteriovenous oxygen difference were calculated as follows:
Parameters of oxygen transport in the skeletal muscle were calculated using the flow in the V. poplitea (flow-popl). Muscular arteriovenous oxygen difference avDO2 mus = CaO2 – CvO2 pop, muscular oxygen delivery DO2 mus = Flow x CaO2, Muscular oxygen consumption VO2 mus = Flow x avDO2 mus, Muscular oxygen extraction ratio ERO2 mus = VO2 mus x DO2 mus x 100 [%].
Skeletal tissue oxygen tensions (peripheral tpO2) were measured in the left gastrocnemius muscle by a microprocessor-controlled fast responding polarographic needle probe of 12.5 µm diameter (Eppendorf needle, Netheler-Hinz, Germany). With this device, 200 single tpO2 values can be determined within a time of five minutes in a conical muscular tissue area of 2 to 3 cm3 at every measurement interval. The probe was driven forward by the microprocessor through the muscle tissue in different directions in steps of 0.7 mm each followed by a reverse step of 0.3 mm every 30 sec after completion of every 20 single tpO2 measurements. This technique prevented compression of muscle tissue or capillaries by the tip of the probe. After 200 single tpO2 measurements, the frequency distribution of the tpO2 values was calculated (Sigma-pO2-Histograph KIMOC 6650, Eppendorf-Netheler-Hinz, Germany). At every measurement interval, 1,200 single tpO2 values were collected. The tissue temperature was measured within the gastrocnemius muscle by a stitch probe and maintained constant by a warming lamp connected to a closed-loop system. The accuracy of tpO2 measurements with polarographic needle probes has been demonstrated in several animal experiments6,35,36 as well as in clinical investigations.32 Due to the fact that the liver moves during the experiment as a consequence of mechanical ventilation, liver oxygen tensions (central tpO2) were measured using a Licox probe (pO2 microprobe, GMS, Germany). This flexible tissue oxygen probe with an electrochemical (polarographic) microcell was inserted in the liver parenchyma and remained at the same place throughout the experiment. The pO2 microprobe averages the tissue oxygen tensions near the tip of the probe in a cylindric tissue layer located concentrically around the long axis of the microcatheter and at a distance of less than 1 mm from its surface. The probes used in the liver were 300 mm long, with a 5-mm sensing area 18 mm from the tip of the catheter. The probes were calibrated by the manufacturer using a special chip-card for each probe. Resulting histograms consequently do not represent a variety of values corresponding to the distribution of tpO2 values in the tissue, but a variety of tpO2 values in an outlined area. One hundred and twenty single tpO2 values (1 every 5 sec) over a period of ten minutes were determined and displayed on the monitor of the connected computer at every time of measurement. Liver tissue temperature was also measured continuously by a thermocoupled microcatheter for temperature compensation of the pO2 value. The accuracy of tpO2 measurement has been demonstrated in animal experiments and in clinical studies.5,37
|
Footnotes |
|---|
Accepted for publication January 4, 2005. Revision accepted May 3, 2005.
|
References |
|---|
|
TOPAbstractIntroductionMethodsResultsDiscussionAPPENDIXReferences |
|---|
2 Fontana JL, Welborn L, Mongan PD, Sturm P, Martin G, Bunger R. Oxygen consumption and cardiovascular function in children during profound intraoperative normovolemic hemodilution. Anesth Analg 1995; 80: 219–25.[Abstract]
3 Freitag M, Standl T, Horn EP, Wilhelm S, Schulte am Esch J. Acute normovolaemic haemodilution beyond a haematocrit of 25%: ratio of skeletal muscle tissue oxygen tension and cardiac index is not maintained in the healthy dog. Eur J Anaesth 2002; 19: 487–94.[Medline]
4 van Bommel J, Trouwborst A, Schwarte L, Siegemund M, Ince C, Henny CP. Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model. Anesthesiology 2002; 97: 660–70.[Medline]
5 Boekstegers P, Riessen R, Seyde W. Oxygen partial pressure distribution within skeletal muscle: indicator of whole body oxygen delivery in patients? Adv Exp Med Biol 1990; 277: 507–14.[Medline]
6 Standl T, Horn P, Wilhelm S, et al. Bovine haemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs. Can J Anaesth 1996; 43: 714–23.
7 Horn EP, Sputtek A, Standl T, Rudolf B, Kuhnl P, Schulte am Esch J. Transfusion of autologous, hydroxyethyl starch-cryopreserved red blood cells. Anesth Analg 1997; 85: 739–45.[Abstract]
8 Standl T, Lipfert B, Reeker W, Schulte am Esch J, Lorke DE. Acute effects of a complete blood exchange with ultra-purified haemoglobin solution or hydroxyethyl starch, on liver and kidney in an animal model (German). Anasthesiol Intensivmed Notfallmed Schmerzther 1996; 31: 354–61.[Medline]
9 Liard JF, Kunert MP. Hemodynamic changes induced by low blood oxygen affinity in dogs. Am J Physiol 1993; 264: R396–401.
10 Standl T, Freitag M, Burmeister MA, Horn EP, Wilhelm S, Schulte am Esch J. Hemoglobin-based oxygen carrier HBOC-201 provides higher and faster increase in oxygen tension in skeletal muscle of anemic dogs than do stored red blood cells. J Vasc Surg 2003; 37: 859–65.[Medline]
11 Buga GM, Gold ME, Fukuto JM, Ignarro LJ. Shear stress-induced release of nitric oxide from endothelial cells grown on beads. Hypertension 1991; 17: 187–93.
12 Mirhashemi S, Ertefai S, Messmer K, Intaglietta M. Model analysis of the enhancement of tissue oxygenation by hemodilution due to increased microvascular flow velocity. Microvasc Res 1987; 34: 290–301.[Medline]
13 Holbeck S, Grande PO. Effects on capillary fluid permeability and fluid exchange of albumin, dextran, gelatin, and hydroxyethyl starch in cat skeletal muscle. Crit Care Med 2000; 28: 1089–95.[Medline]
14 Horn EP, Standl T, Wilhelm S, Jacobs EE, Freitag U, Freitag M, Schulte am Esch J. Bovine hemoglobin increases skeletal muscle oxygenation during 95% artificial arterial stenosis. Surgery 1997; 121: 411–8.[Medline]
15 Nolte D, Botzlar A, Pickelmann S, Bouskela E, Messmer K. Effects of diaspirin-cross-linked hemoglobin (DCLHbTM) on the microcirculation of striated skin muscle in the hamster: a study on safety and toxicity. J Lab Clin Med 1997; 130: 314–27.[Medline]
16 Sielenkamper AW, Eichelbronner O, Martin CM, Madorin SW, Chin-Yee IH, Sibbald WJ. Diaspirin cross-linked hemoglobin improves mucosal perfusion in the ileum of septic rats. Crit Care Med 2000; 28: 782–7.[Medline]
17 Slanetz PJ, Lee R, Page R, Jacobs EE Jr, LaRaia PJ, Vlahakes GJ. Hemoglobin blood substitutes in extended preoperative autologous blood donation: an experimental study. Surgery 1994; 115: 246–54.[Medline]
18 Standl TG, Reeker W, Redmann G, Kochs E, Werner C, Schulte am Esch J. Haemodynamic changes and skeletal muscle oxygen tension during complete blood exchange with ultrapurified polymerized bovine haemoglobin. Intensive Care Med 1997; 23: 865–72.[Medline]
19 Page TC, Light WR, Hellums JD. Prediction of microcirculatory oxygen transport by erythrocyte/hemoglobin solution mixtures. Microvasc Res 1998; 56: 113–26.[Medline]
20 Hughes GS Jr, Antal EJ, Locker PK, Francom SF, Adams WJ, Jacobs EE Jr. Physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans. Crit Care Med 1996; 24: 756–64.[Medline]
21 Faivre-Fiorina B, Caron A, Fassot C, et al. Presence of hemoglobin inside aortic endothelial cells after cell-free hemoglobin administration in guinea pigs. Am J Physiol 1999; 276: H766–70.
22 LaMuraglia GM, O’Hara PJ, Baker WH, et al. The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg 2000; 31: 299–308.[Medline]
23 Standl T, Wilhelm S, Horn EP, Burmeister M, Gundlach M, Schulte am Esch J. Preoperative hemodilution with bovine hemoglobin. Acute hemodynamic effects in liver surgery patients (German). Anaesthesist 1997; 46: 763–70.[Medline]
24 Biro GP, Taichman GC, Lada B, Keon WJ, Rosen AL, Sehgal LR. Coronary vascular actions of stroma-free hemoglobin preparations. Artif Organs 1988; 12: 40–50.[Medline]
25 Gilroy D, Shaw C, Parry E, Olding-Smee W. Detection of a vasocontrictor factor in stroma-free haemoglobin solutions. J Trauma 1988; 28: 1312–6.[Medline]
26 Gulati A, Sharma AC, Burhop KE. Effect of stroma-free hemoglobin and diaspirin cross-linked hemoglobin on the regional circulation and systemic hemodynamics. Life Sci 1994; 55: 827–37.[Medline]
27 Sherman IA, Dlugosz JA, Perelman V, Hsia CJ, Wong LT, Condie RM. Systemic hemodynamic and hepatic microvascular responses to a 33% blood volume exchange with whole blood, stroma-free hemoglobin, and oxypolyhemoglobin solutions. Biomater Artif Cells Immobilization Biotechnol 1993; 21: 537–51.[Medline]
28 Federspiel WJ. Pulmonary diffusing capacity: implications of two-phase blood flow in capillaries. Respir Physiol 1989; 77: 119–34.[Medline]
29 Page TC, Light WR, McKay CB, Hellums JD. Oxygen transport by erythrocyte/hemoglobin solution mixtures in an in vitro capillary as a model of hemoglobin-based oxygen carrier performance. Microvasc Res 1998; 55: 54–64.[Medline]
30 Driessen B, Jahr JS, Lurie F, Griffey SM, Gunther RA. Effects of haemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) on intestinal perfusion and oxygenation in a canine hypovolaemia model. Br J Anaesth 2001; 86: 683–92.
31 Zander R. Failure to prove the effectiveness of hemoglobin solutions as oxygen carriers in the paper of Horn et al. Anaesthesist (1998) 47: 116–123. Anaesthetist 1998; 47: 998–1003.[Medline]
32 Standl T, Burmeister MA, Schroeder F, et al. Hydroxyethyl starch (HES) 130/0.4 provides larger and faster increases in tissue oxygen tension in comparison with prehemodilution values than HES 70/0.5 or HES 200/0.5 in volunteers undergoing acute normovolemic hemodilution. Anesth Analg 2003; 96: 936–43.
33 Knudson MM, Lee S, Erickson V, Morabito D, Derugin N, Manley GT. Tissue oxygen monitoring during hemorrhagic shock and resuscitation: a comparison of lactated Ringer’s solution, hypertonic saline dextran, and HBOC-201. J Trauma 2003; 54: 242–52.[Medline]
34 Ragheb J, Buggy DJ. Tissue oxygen tension (PTO2) in anaesthesia and perioperative medicine (Editorial). Br J Anaesth 2004; 92: 464–8.
35 Fleckenstein W, Schaffler A, Heinrich R, Petersen C, Gunderoth-Palmowski M, Nollert G. On the differences between muscle pO2 measurements obtained with hypodermic needle probes and with multiwire surface probes. Part 2: Systemic diffusion error of the multiwire surface pO2 probe when applied on the tissue. In: Ehrly AM, Fleckenstein W, Hauss J, Huch R (Eds). Clinical Oxygen Pressure Measurement. Berlin: Blackwell Ueberreuter Wissenschaft; 1990; 268–78.
36 Fleckenstein W, Weiss C. A comparison of pO2 histograms from rabbit hind-limb muscles obtained by simultaneous measurements with hypodermic needle electrodes and with surface electrodes. Adv Exp Med Biol 1984; 169: 447–55.[Medline]
37 Noldge GF, Priebe HJ, Geiger K. Splanchnic hemodynamics and oxygen supply during acute normovolemic hemodilution alone and with isoflurane-induced hypotension in the anesthetized pig. Anesth Analg 1992; 75: 660–74.
This article has been cited by other articles:
 |
|
 |
|
  R. I. Hall The utility of hemoglobin based oxygen carriers (HBOC) - can animal studies help?/L'utilite des transporteurs d'oxygene a base d'hemoglobine (HBOC) - les etudes animales peuventelles aider ? Can J Anesth, November 1, 2005; 52(9): 895 - 898. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
