Antioxidative Resuscitation Solution Prevents Leukocyte Adhesion in the Liver after Hemorrhagic Shock

Bauer, Clemens; Walcher, Felix; Holanda, M.; Mertzlufft, F.; Larsen, Reinhard; Marzi, Ingo

doi:10.1097/00005373-199905000-00019

Cited by 33 publications

(19 citation statements)

References 21 publications

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“…It should be noted that the SIP cardioprotective effect seen in our study may attribute, in part, to haemodilution that reduces the availability of circulating neutrophils, and in part to the potential cardioprotective effects of D-HES [11]. Nevertheless, it is safe to say that it is primarily the SIP rather than the haemodilution and D-HES that have contributed mostly to the cardioprotection seen in the SIP group.…”

Section: Discussionmentioning

confidence: 62%

Systemic ischemic preconditioning plus hemodilution enhanced early functional recovery of reperfused heart in the rabbits*1

Xia

Luo

et al. 2004

Interactive Cardiovascular and Thoracic Surgery

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We investigated whether transient systemic ischemia can precondition the heart against the ensuing ischemic insult. Rabbits were randomly divided into systemic ischemic preconditioning (SIP), hemodilution (HD) and control (C) groups. SIP was induced by rapidly withdrawing blood from femoral artery and maintaining the mean artery pressure at 50 mmHg for 10 min. Afterwards, 50% of the withdrawn blood was re-infused with equal volumes of 6% deferoxamine-conjugated hydroxyethyl-starch (D-HES). Hemodilution in HD group was achieved by withdrawing blood at 8 ml/kg accompanied by concomitant infusion of equal volumes of D-HES. Animals were subjected to 30 min of coronary artery occlusion followed by 120 min of reperfusion. Cardiac output (CO) (thermodilution method), plasma malondialdehyde and nitric oxide content were measured at baseline and until 120 (R120) min of reperfusion. At R120, CO in group-C was significantly lower than its baseline value, accompanied by a significant reduction in nitric oxide production and increase in malondialdehyde concentration; CO in group-SIP and group-HD maintained at baseline levels throughout reperfusion. At R120, CO in group-SIP, but not in group-HD, was significantly higher than that in group-C. It is concluded that transient SIP followed by hemodilution with D-HES facilitates early functional recovery of the ischemic-reperfused rabbit hearts.

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Section: Discussionmentioning

confidence: 62%

Systemic ischemic preconditioning plus hemodilution enhanced early functional recovery of reperfused heart in the rabbits*1

Xia

Luo

et al. 2004

Interactive Cardiovascular and Thoracic Surgery

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“…Recently, modifications such as hypertonic hyperosmotic resuscitation solution have been introduced [30]. Furthermore, colloids like deferoxamine-conjugated hydroxyethyl starch solution (HAES-DFO) have been shown to beneficially affect the microcirculation [31]. Also, HAES might beneficially influence the reperfusion injury by reducing lipid peroxidation [31].…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiological understanding of postshock inflammation suggests the necessity of both adequate volume replacement and immunomodulatory therapy [8,31]. There is evidence that FFP leads to an increase in cardiac output, left ventricular stroke volume, pulmonary capillary wedge pressure, and increased IgG levels [33].…”

Section: Discussionmentioning

confidence: 99%

“…Also, natural antibodies and serum complement seem to play an important role in the clearance of pathogenic substances from the circulation [26]. According to a number of studies [8,12], microcirculatory disturbances after hemorrhagic shock are closely related to the inflammatory response, suggesting that anti-inflammatory therapy is necessary to avoid further tissue injury and organ failure [5,10,31]. The aim of this study was to evaluate the effect of SPS in comparison to gelatine and albumin on the systemic circulation and hepatic microcirculation after hemorrhagic shock in rats.…”

Section: Introductionmentioning

confidence: 99%

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Supplementary Administration of Serum Protein Solution during Shock Resuscitation in the Rat

et al. 2004

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European Journal of TraumaAb stract Background and Purpose: Hemorrhagic shock initiates an inflammatory response that leads to microcirculatory disturbances. Resuscitation with crystalloids and colloids may restore mean arterial blood pressure but does not specifically inhibit inflammatory cascades. In this study, a serum protein solution (SPS) was administered during shock resuscitation in order to investigate hepatic microcirculation following hemorrhagic shock. The effect of this SPS was compared with two other substances, albumin and gelatine. Material and Methods: Using an animal model, hemorrhagic shock was induced in 36 rats for 60 min at 40 mmHg. Afterwards, resuscitation was started with either gelatine (3%), human serum albumin (5%), SPS consisting of albumin and globulins (5%), a combination of gelatine/albumin (1 : 1), or a combination of gelatine/SPS (1 : 1). After a resuscitation period of 6 h, the hepatic microcirculation, leukocyte-endothelium interaction and sinusoidal width were examined using intravital microscopy. Results: Values for hemoglobin, platelets, white blood cells and base deficit did not differ between the groups. In contrast to albumin and SPS, gelatine restored mean arterial blood pressure most effectively. In addition, the combination of SPS/gelatine attenuated permanent leukocyte adhesion significantly. Except for the SPS group, erythrocyte blood flow in the liver was significantly reduced in all shock groups. Conclusion: While gelatine is most effective in the restoration of the systemic circulation, the addition of SPS might allow nonspecific attenuation of leukocyte adhesion in the liver. Moreover, SPS might improve the reduced erythrocyte blood flow after hemorrhagic shock.

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“…Desferoxamine complexed with a large starch has limited cellular permeability (Paller and Hedlund 1994) but it is still able to mitigate hepatic dysfunction after H/R (Bauer et al 1999;Rana et al 2002;Rose et al 2000) suggesting an important role for extracellular iron in this process. The biochemical species of this iron is unknown, but the possibility that ferrous iron could be involved was suggested by our findings that the ferroxidase activity of plasma ceruloplasmin was disrupted in hemorrhage (Atkins et al 2005;Dubick et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Ferrous iron is found in mesenteric lymph bound to TIMP-2 following hemorrhage/resuscitation

et al. 2011

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Extracellular iron has been implicated in the pathogenesis of post-injury organ failure. However, the source(s) and biochemical species of this iron have not been identified. Based upon evidence that distant organ injury results from an increase in intestinal permeability, we looked for ferrous iron in mesenteric lymph in anesthetized rats undergoing hemorrhage and fluid resuscitation (H/R). Ferrous iron increased in lymph from 4.7 nmol/mg of protein prior to hemorrhage to 86.6 nmol/mg during resuscitation. Utilizing immuno-spin trapping in protein fractions that were rich in iron, we tentatively indentified protein carrier(s) of ferrous iron by MALDI-TOF MS. One of the identified proteins was the metalloproteinase (MMP) inhibitor, TIMP-2. Antibody to TIMP-2 immunoprecipitated 74% of the ferrozine detectable iron in its protein fraction. TIMP-2 binds iron in vitro at pH 6.3, which is typical of conditions in the mesentery during hemorrhage, but it retains the ability to inhibit the metalloproteases MMP-2 and MMP-9. In summary, there is a large increase in extracellular ferrous iron in the gut in H/R demonstrating dysregulation of iron homeostasis. We have identified, for the first time, the binding of extracellular iron to TIMP-2.

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Antioxidative Resuscitation Solution Prevents Leukocyte Adhesion in the Liver after Hemorrhagic Shock

Abstract: The results suggest that HES-DFO effectively reduces oxygen radical formation during the initial resuscitation period, thus, attenuating pathologically enhanced leukocyte adhesion and improving hepatic microcirculation.

Cited by 33 publications

References 21 publications

Systemic ischemic preconditioning plus hemodilution enhanced early functional recovery of reperfused heart in the rabbits*1

Systemic ischemic preconditioning plus hemodilution enhanced early functional recovery of reperfused heart in the rabbits*1

Supplementary Administration of Serum Protein Solution during Shock Resuscitation in the Rat

Ferrous iron is found in mesenteric lymph bound to TIMP-2 following hemorrhage/resuscitation

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