Application of negative tissue interstitial pressure improves functional capillary density after hemorrhagic shock in the absence of volume resuscitation

Background Scavenging of nitric oxide by hemoglobin-based oxygen carriers could aggravate microcirculatory failure in splanchnic organs after hemorrhagic shock as a consequence of vasoconstrictive side effects. The aim of this study was to compare the effects of two recombinant human hemoglobin solutions, a second-generation product bearing reduced nitric oxide-scavenging properties (rHb2.0) due to site directed mutagenesis of the heme pocket and a first-generation recombinant hemoglobin (rHb1.1) with scavenging capacity similar to native hemoglobin, on the pancreatic microcirculation after hemorrhagic shock. Methods Twenty-eight pentobarbital-anesthetized rats were bled to a mean arterial pressure of 40 mmHg and maintained at this level for 1 h. Using an intravital microscope, the length of erythrocyte-perfused pancreatic capillaries per observation area (functional capillary density) were measured in animals resuscitated by volumes of hydroxyethyl starch, rHb1.1, or rHb2.0 equivalent to the shed blood volume. Animals without shock induction served as control. Results As compared with control (438 +/- 10 cm(-1)), animals treated with hydroxyethyl starch (315 +/- 44 cm(-1)) and rHb1.1 (288 +/- 67 cm(-1)) showed a significant reduction of functional capillary density after 2 h of resuscitation. rHb2.0 was able to restore functional capillary density (410 +/- 42 cm(-1)) and mean arterial pressure to baseline values. Conclusion rHb2.0 was effectively able to restore pancreatic microcirculation after hemorrhagic shock. This may be related to the compound's effective lack of nitric oxide-scavenging properties. This hemoglobin solution or ones similar to it might be uniquely valuable for resuscitation from hemorrhagic shock.

Download Full-text

Diaspirin Cross-linked Hemoglobin Effectively Restores Pancreatic Microcirculatory Failure in Hemorrhagic Shock

Anesthesiology ◽

10.1097/00000542-199912000-00029 ◽

1999 ◽

Vol 91 (6) ◽

pp. 1754-1754 ◽

Cited By ~ 21

Author(s):

Ernst von Dobschuetz ◽

Tomas Hoffmann ◽

Konrad Messmer

Keyword(s):

Lipid Peroxidation ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Hemorrhagic Shock ◽

Whole Blood ◽

Capillary Density ◽

Pancreatic Tissue ◽

Functional Capillary Density ◽

Reactive Material ◽

Area Functional

Background Microvascular reperfusion failure of splanchnic organs is a crucial hallmark in organ damage induced by hemorrhagic shock, which should be prevented by a resuscitation solution. Because the vasoactive properties of the hemoglobin-based oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) could adversely influence restoration of pancreatic capillary perfusion during resuscitation, the authors investigated its effects on the microcirculation of the rat pancreas in comparison with whole blood and 6% hydroxyethylstarch resuscitation from severe hemorrhagic shock. Methods Twenty-eight pentobarbital-anaesthetized rats were bled to a mean arterial pressure (MAP) of 40 mmHg and maintained at this level for 1 h. Using an intravital microscope, mean arterial pressure, the length of erythrocyte-perfused pancreatic capillaries per observation area (functional capillary density), the adherence of leukocytes in postcapillary venules, and pancreatic lipid peroxidation, measured as thiobarbituric acid-reactive material in pancreatic tissue, were determined in animals resuscitated by volumes of hydroxyethylstarch, DCLHb, and whole blood (WB) equivalent to the shed blood volume or in control animals without shock induction for a period of 2 h after resuscitation. Results Compared with control animals (366+/-28 cm(-1)), animals resuscitated with DCLHb (294+/-45 cm(-1)), WB (306+/-11 cm(-1)), and hydroxyethylstarch (241+/-34 cm(-1)) showed a significant reduction of functional capillary density after 2 h of resuscitation. DCLHb was as effective as WB and superior to hydroxyethylstarch in restoring functional capillary density and mean arterial pressure. Leukocyte adherence in postcapillary venules was not enhanced by DCLHb (369+/-148/mm2) infusion when compared with hydroxyethylstarch- (615+/-283/mm2) and WB-treated (510+/-415/mm2) animals. Lipid peroxidation of pancreatic tissue was significantly elevated after treatment with both oxygen-carrying solutions compared with hydroxyethylstarch. Conclusion DCLHb is as effective as WB for preservation of the pancreatic microcirculation.

Download Full-text

Shenfu injection improves cerebral microcirculation and reduces brain injury in a porcine model of hemorrhagic shock; SFI reduces brain injury after hemorrhagic shock

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211100 ◽

2021 ◽

pp. 1-11

Author(s):

Junyuan Wu ◽

Zhiwei Li ◽

Wei Yuan ◽

Qiang Zhang ◽

Yong Liang ◽

...

Keyword(s):

Brain Injury ◽

Hemorrhagic Shock ◽

Interleukin 6 ◽

Aquaporin 4 ◽

Flow Index ◽

Sham Operation ◽

Volume Resuscitation ◽

Cerebral Microcirculation ◽

Shenfu Injection ◽

Tnf Α

BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n = 8), saline group (SA, n = 8) or sham operation group (SO, n = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.

Download Full-text

A Comparison of the Hemoglobin-Based Oxygen Carrier HBOC-201 to Other Low-Volume Resuscitation Fluids in a Model of Controlled Hemorrhagic Shock

Journal of Trauma and Acute Care Surgery ◽

10.1097/01.ta.0000084519.47163.77 ◽

2003 ◽

Vol 55 (4) ◽

pp. 747-754 ◽

Cited By ~ 35

Author(s):

CPT James B. Sampson ◽

CPT Michael R. Davis ◽

MAJ Deborah L. Mueller ◽

LT Vikram S. Kashyap ◽

LT Donald H. Jenkins ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Oxygen Carrier ◽

Volume Resuscitation ◽

Low Volume

Download Full-text

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00394.2006 ◽

2006 ◽

Vol 291 (5) ◽

pp. H2445-H2452 ◽

Cited By ~ 60

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.

Download Full-text

Red Blood Cell Mechanics and Functional Capillary Density

International Journal of Microcirculation ◽

10.1159/000179026 ◽

1995 ◽

Vol 15 (5) ◽

pp. 250-254 ◽

Cited By ~ 11

Author(s):

T.W. Secomb ◽

R. Hsu

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Cell Mechanics ◽

Capillary Density ◽

Functional Capillary Density

Download Full-text

Glucose administration during volume resuscitation using dextran-40 from hemorrhagic shock ameliorates acid/base-imbalance in fasted rats under sevoflurane anesthesia

BioScience Trends ◽

10.5582/bst.2013.v7.3.138 ◽

2013 ◽

Keyword(s):

Hemorrhagic Shock ◽

Volume Resuscitation ◽

Sevoflurane Anesthesia ◽

Acid Base ◽

Dextran 40 ◽

Glucose Administration ◽

Fasted Rats

Download Full-text

Shenfu Injection Improves Cerebral Microcirculation and Reduces Brain Injury in a Porcine Model of Hemorrhagic Shock

10.21203/rs.3.rs-34176/v1 ◽

2020 ◽

Author(s):

Junyuan Wu ◽

Zhiwei Li ◽

Wei Yuan ◽

Qiang Zhang ◽

Yong Liang ◽

...

Keyword(s):

Brain Injury ◽

Hemorrhagic Shock ◽

Interleukin 6 ◽

Aquaporin 4 ◽

Flow Index ◽

Sham Operation ◽

Volume Resuscitation ◽

Cerebral Microcirculation ◽

Sham Operation Group ◽

Tnf Α

Abstract Background: The aim of this study was to clarify effects of Shenfu infusion (SFI) on cerebral microcirculation and brain injury after hemorrhagic shock (HS).Methods: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n=8), saline group (SA, n=8) or sham operation group (SO, n=5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40 ± 3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin 6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured.Results: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin 6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group.Conclusions: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.

Download Full-text

Systemic and microcirculatory effects of autologous whole blood resuscitation in severe hemorrhagic shock

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.6.h2035 ◽

1999 ◽

Vol 276 (6) ◽

pp. H2035-H2043 ◽

Cited By ~ 16

Author(s):

Heinz Kerger ◽

Klaus F. Waschke ◽

Klaus V. Ackern ◽

Amy G. Tsai ◽

Marcos Intaglietta

Keyword(s):

Metabolic Acidosis ◽

Hemorrhagic Shock ◽

Whole Blood ◽

Tissue Perfusion ◽

Capillary Density ◽

Shed Blood ◽

Syrian Golden Hamsters ◽

Autologous Whole Blood ◽

Significant Impairment ◽

Main Determinants

Systemic and microcirculatory effects of autologous whole blood resuscitation after 4-h hemorrhagic shock with a mean arterial pressure (MAP) level of 40 mmHg were investigated in 63 conscious Syrian golden hamsters. Microcirculation of skeletal skin muscle and subcutaneous connective tissue was visualized in a dorsal skinfold. Shed blood was retransfused within 30 min after 4 h. Animals were grouped into survivors in good (SG) and poor condition (SP) and nonsurvivors (NS) according to 24-h outcome after resuscitation and studied before shock, during shock (60, 120, and 240 min), and 30 min and 24 h after resuscitation. Microvascular and interstitial[Formula: see text] values were determined by phosphorescence decay. Shock caused a significant increase of arterial[Formula: see text] and decrease of[Formula: see text], pH, and base excess. In the microcirculation, there was a significant decrease in blood flow (Q˙B), functional capillary density (FCD; capillaries with red blood cell flow), and interstitial [Formula: see text][1.8 ± 0.8 mmHg (SG), 1.3 ± 1.3 mmHg (SP), and 0.9 ± 1.1 mmHg (NS) vs. 23.0 ± 6.1 mmHg at control]. Blood resuscitation caused immediate MAP recompensation in all animals, whereas metabolic acidosis, hyperventilation, and a significant interstitial [Formula: see text] decrease (40–60% of control) persisted. In NS (44.4% of the animals), systemic and microcirculatory alterations were significantly more severe both in shock and after resuscitation than in survivors. Whereas in SG (31.8% of the animals) there was only a slight (15–30%) but still significant impairment of microscopic tissue perfusion (Q˙B, FCD) and oxygenation at 24 h, SP (23.8% of the animals) showed severe metabolic acidosis and substantial decreases (≥50%) of FCD and interstitial[Formula: see text]. FCD, interstitial[Formula: see text], and metabolic state were the main determinants of shock outcome.

Download Full-text

Hypertonic hydroxyethyl starch restores hepatic microvascular perfusion in hemorrhagic shock

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.266.5.h1927 ◽

1994 ◽

Vol 266 (5) ◽

pp. H1927-H1934 ◽

Cited By ~ 2

Author(s):

B. Vollmar ◽

G. Lang ◽

M. D. Menger ◽

K. Messmer

Keyword(s):

Hemorrhagic Shock ◽

Hydroxyethyl Starch ◽

Small Volume ◽

Microvascular Perfusion ◽

Volume Resuscitation ◽

Shock Model ◽

Intravital Fluorescence Microscopy ◽

Ringer Lactate ◽

Endothelial Lining ◽

Perfusion Failure

The influence of small-volume resuscitation (hypertonic saline-10% hydroxyethyl starch, HS/HES) on liver microcirculation (intravital fluorescence microscopy) was studied in a nonheparinized hemorrhagic shock model [mean arterial pressure (MAP) 40 mmHg for 1 h] in rats. Resuscitation was performed with Ringer lactate (RL, 4-fold shed volume/20 min; n = 7), 10% hydroxyethyl starch 200/0.6 (HES, shed volume/5 min; n = 6), or 7.2% NaCl-10% hydroxyethyl starch 200/0.6 (HS/HES, 10% shed volume/2 min; n = 7). One hour after resuscitation, MAP increased in all groups, but it did not return to preshock values (P < 0.05). HES (16 +/- 2% nonperfused sinusoids) and HS/HES (14 +/- 2% nonperfused sinusoids), but not RL (24 +/- 2% nonperfused sinusoids), reduced (P < 0.05) shock-induced sinusoidal perfusion failure (28 +/- 3%) with restoration of leukocyte velocity in sinusoids (S) and postsinusoidal venules (V). Shock-induced stasis/adherence of leukocytes was further increased (P < 0.05) after resuscitation with RL (S, 38 +/- 6%; V, 55 +/- 20%) and HES (S, 31 +/- 8%; V, 23 +/- 14%). In contrast, resuscitation with HS/HES prevented increased leukocyte stasis in sinusoids (-4 +/- 4%) as well as adherence to endothelial lining of postsinusoidal venules (-5 +/- 10%). We conclude that replacement of only 10% of actual blood loss by means of small-volume resuscitation (HS/HES) can restore hepatic microvascular perfusion and prevent reperfusion-induced leukocyte stasis/adherence.

Download Full-text