Systemic Intravenous Infusion of Bovine Hemoglobin Significantly Reduces Microcirculatory Dysfunction in Experimentally Induced Pancreatitis in the Rat

Strate, Tim; Mann, Oliver; Kleinhans, Helge; Schneider, Claus; Knoefel, Wolfram Trudo; Yekebas, Emre F.; Standl, Thomas; Bloechle, C.; Izbicki, Jakob R.

doi:10.1097/01.sla.0000094442.12395.98

Cited by 39 publications

(31 citation statements)

References 16 publications

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“…In SAP, the production of a large number of cytokines and vasoactive substances can, directly or indirectly, give rise to decreased local blood flow and blood flow velocity, leukocyte adhesion, and increased capillary permeability, which can cause microcirculatory disturbances (Strate et al, 2003;von Dobschuetz et al, 2004). Microcirculatory disturbance is one of the trigger factors for the development of acute pancreatitis (AP) (Foitzik et al, 2000;Qu et al, 2003).…”

mentioning

confidence: 99%

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

Zhang

Chengjun

et al. 2012

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods: The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results: The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Conclusions: Both dexamethasone and Salvia miltiorrhiza can reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple organs of rats with SAP.

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confidence: 99%

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

Zhang

Chengjun

et al. 2012

J. Zhejiang Univ. Sci. B

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“…In contrast, animal studies have shown improved tissue oxygenation during blood exchange, restoration of the pancreatic microcirculation and tissue oxygen tensions, and reduced acidosis with better mucosal integrity of the intestine after resuscitation from hemorrhagic shock with different HBOC [16,24,25]. In experimental acute pancreatitis bovine HBOC-301 was able to significantly reduce histologic tissue damage in rats [26]. In acute porcine pancreatitis hemodilution with HES plus HBOC-301 improved the pancreatic microcirculation and tissue oxygenation and increased the 6-day survival rate [27].…”

Section: Animal Experiments With Hemoglobin-based Oxygen Carriersmentioning

confidence: 91%

“…Pulmonary gas exchange can possibly be improved with HBOC entering compressed capillaries in zone I of the lung in critically ill patients [55]. Because of the vasopressor properties (NO scavenging) in combination with improved perfusion and oxygen release on the microcirculatory site, HBOC may particularly be useful in the treatment of sepsis and acute pancreatitis [26,27]. Animal experiments of septic shock demonstrated hemodynamic stabilization without significant adverse effects on regional organ blood flow using cell-free Hb [56].…”

Section: Possible Indications Of Hboc In the Futurementioning

confidence: 99%

Artificial Oxygen Carriers: Hemoglobin-Based Oxygen Carriers – Current Status 2004

Standl¹

2004

Transfus Med Hemother

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Because of an impending shortfall of allogeneic blood products within the next decades and ongoing problems associated with relevant costs for testing and storage of banked red blood cell (RBC) units, the development of alternatives has been intensified during the last 15 years. Modern chemically modified hemoglobin- based oxygen carriers (HBOC) are free of RBC membrane remnants, renal toxicity, and ABO antigens which allows transfusion without knowledge of the respective blood group of a patient. Bovine polymerized cell-free hemoglobin can be stored at room temperature for 3 years. In contrast to the perfluorocarbon solutions, HBOC can be applied at room air oxygen concentrations. Animal experiments have shown that HBOC can compensate for intravascular volume deficits in hemorrhagic shock, including restoration of colloid osmotic pressure and organ perfusion, and deliver oxygen to organs and tissues during nearly complete blood exchange. Chemical modifications of HBOC are able to reduce the vasoconstrictive side effect of HBOC which is caused by NO scavenging. In spite of vasoconstriction, the increased oxygen extraction in presence of HBOC in combination with the plasmatic oxygen transport provides enhanced tissue oxygenation even in post-stenotic tissues. HBOC seem to improve the diffusive oxygen transport at the microcirculatory site, thus decreasing tissue damage in acute pancreatitis and tissue injury in the heart and brain after ischemia/reperfusion. Clinical studies showed that the perioperative use of different HBOC (Hemopure®, PolyHeme®, Hemolink®, HemAssist®) can reduce the number of allogeneic RBC units and increase the avoidance rate of allogeneic transfusion in emergency bleeding as well as in vascular, cardiac and noncardiac surgery. Polymerized HBOC appear to have a lower potential of side effects in comparison to intramolecularly crosslinked preparations. However, HBOC-201 (Hemopure) is the only substance which has been licensed for the treatment of patients until now.

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“…In recent years, some studies have found that, during the development and progression of SAP, the premature activation of pancreatic enzymes in acinar cells and excessive inflammatory reaction can induce the production of a large number of cytokines and vasoactive substances that are able to, directly or indirectly, give rise to the decrease in local blood flow, blood flow velocity, leukocyte adhesion and capillary density as well as the increase in capillary permeability, thereby inducing microcirculation disturbance [8,9]. In turn, microcirculation disturbance is one of the important factors that can induce the production of inflammatory mediators.…”

Section: Discussionmentioning

confidence: 99%

Effect of Baicalin on Inflammatory Mediator Levels and Microcirculation Disturbance in Rats With Severe Acute Pancreatitis

Zhang

Tian

et al. 2009

Pancreas

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AbstractsObjective: To investigate the effect of Bacailin on inflammatory mediator levels and microcirculation disturbance in severe acute pancreatitis (SAP) rats and explore its therapeutic mechanism on this disease. Methods: SAP model rats were randomly divided into model control group and Baicalin treated group, 45 rats in each group. The same number of normal rats were included in sham-operated group. These groups were further subdivided into 3 h, 6 h and 12 h subgroups, respectively (15 rats in each subgroup). At 3, 6 and 12 hours after operation, rats were killed to conduct the following experiments: (1) to examine the mortality rates of rats, the ascites volume and pancreatic pathological changes in each group; (2) to determine the contents of amylase, PLA 2 , TXB 2 , PGE 2 , PAF and IL-1β in blood as well as the changes in blood viscosity.Results: (1) Compared to model control group, treatment with Baicalin is able to improve the pathological damage of the pancreas, lower the contents of amylase and multiple inflammatory mediators in blood, decrease the amount of ascitic fluid and reduce the mortality rates of SAP rats (P<0.01, P<0.01 or P<0.001); (2) at 3 hours after operation, the low-shear whole blood viscosity (1/s)(mPa.s) in Baicalin treated group was significantly lower than that in model control group (P<0.01); at 12 hours after operation, both the high-shear (200/s) (mPa.s) and low-shear whole blood viscosity (1/s) (mPa.s) in Baicalin treated group were also significantly lower than those in model control group (P<0.01 for all). Conclusion: Baicalin, as a new drug, has good prospects in the treatment of SAP since it can exert therapeutic effects on this disease through inhibiting the production of inflammatory mediators, lowering blood viscosity, improving microcirculation and mitigating the pathological damage of the pancreas.

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Systemic Intravenous Infusion of Bovine Hemoglobin Significantly Reduces Microcirculatory Dysfunction in Experimentally Induced Pancreatitis in the Rat

Abstract: In severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.

Cited by 39 publications

References 16 publications

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

Artificial Oxygen Carriers: Hemoglobin-Based Oxygen Carriers – Current Status 2004

Effect of Baicalin on Inflammatory Mediator Levels and Microcirculation Disturbance in Rats With Severe Acute Pancreatitis

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