The Use of Insulin and Glucose during Resuscitation from Hemorrhagic Shock Increases Hepatic ATP

Chang, Craig G.; Way, Charles W. Van; Dhar, Animesh; Helling, Thomas S.; Hahn, Yoav

doi:10.1006/jsre.2000.5857

Cited by 28 publications

(23 citation statements)

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“…Some investigators have shown that the reduction in immunological mediators, such as tumor necrosis factor-␣, improves outcome indicators (23,41). Others have shown that there is severe hepatic energy depletion during hemorrhagic shock and that improvement in the hepatocellular energy state reduces liver dysfunction (7,38,40). Overall, these studies show that outcome after resuscitation is dependent on many factors.…”

mentioning

confidence: 81%

Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

Mongan

Capacchione

West

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine. Am J Physiol Heart Circ Physiol 283: H1634-H1644, 2002. First published June 20, 2002 10.1152/ ajpheart.01073.2001.-Previous studies have shown that the liver is the first organ to display signs of injury during hemorrhagic shock. We examined the mechanism by which pyruvate can prevent liver damage during hemorrhagic shock in swine anesthetized with halothane. Thirty minutes after the induction of a 240-min controlled arterial hemorrhage targeted at 40 mmHg, hypertonic sodium pyruvate (0.5 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) was infused to achieve an arterial concentration of 5 mM. The volume and osmolality effects of pyruvate were matched with 10% saline (HTS) and 0.9% saline (NS). Although the peak hemorrhage volume increased significantly in both the pyruvate and HTS group, only the pyruvate treatment was effective in delaying cardiovascular decompensation. In addition, pyruvate effectively maintained the NADH/NAD redox state, as evidenced by increased microdialysate pyruvate levels and a significantly lower lactateto-pyruvate ratio. Pyruvate also prevented the loss of intracellular antioxidants (GSH) and a reduction in the GSH-to-GSSG ratio. These beneficial effects on the redox environment decreased hepatic cellular death by apoptosis. Pyruvate significantly increased the ratio of Bcl-Xl (antiapoptotic molecule)/Bax (proapoptotic molecule), prevented the release of cytochrome c from mitochondria, and decreased the fragmentation of caspase 3 and poly(ADP ribose) polymerase (DNA repair enzyme). These beneficial findings indicate that pyruvate infused 30 min after the onset of severe hemorrhagic shock is effective in maintaining the redox environment, preventing the loss of the key antioxidant GSH, and decreasing early apoptosis indicators. glutathione; redox state; caspases DESPITE ADVANCES IN THE EARLY CARE of trauma victims over the past two decades, multiple organ failure (MOF) continues to be a major factor in the morbidity and mortality that occurs after resuscitation from hemorrhagic shock (16). While there are numerous factors that influence the development of MOF, there is increasing evidence that hepatic dysfunction plays a central role (21,24,42,43). Experimental studies have shown that despite acute aggressive resuscitation, there is a consistent depression in microvascular blood flow that results in hypoperfusion and progressive hepatic dysfunction (32,42,43). This suggests that despite the restoration of global oxygen delivery, additional pharmacological therapies are needed to prevent or reverse ongoing hepatotoxicity. However, the precise mechanisms of hepatocellular dysfunction after severe hemorrhagic shock are not well defined. Some investigators have shown that the reduction in immunological mediators, such as tumor necrosis factor-␣, improves outcome indicators (23,41). Others have shown that there is severe hepatic energy depletion during hemorrhagic shock and that improvement in the hepatoce...

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mentioning

confidence: 81%

Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

Mongan

Capacchione

West

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Glucose use in the liver is dependent on both GLUT-2 and glucokinase enzyme activities; plasma insulin levels affect hepatic glucokinase enzyme activities, although glucose uptake via GLUT-2 is independent of insulin (13). It was reported that co-administration of glucose with insulin during resuscitation from hemorrhagic shock increases hepatic ATP (14). Lactate is metabolized by lactate dehydrogenase in the liver, and the metabolite (i.e., pyruvate) is used as an energy substrate.…”

Section: Discussionmentioning

confidence: 99%

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

2013

Biosci Trends

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“…Hemorrhage induces overexpression of iNOS and HSP70i proteins, increases in cellular caspase-3 activity [14], and reduction in ATP [15][16][17][18]. iNOS overexpression appears early and it leads to the NO production and its direct and indirect effects.…”

Section: Discussionmentioning

confidence: 99%

“…Sham-treated mouse organs displayed no changes in the basal levels of c-JUN, KLF6, and iNOS. In addition to changes in this series of stress-related proteins listed above, hemorrhage also increases cellular caspase-3 activity [14], reduces cellular ATP levels [14][15][16][17][18], and elevated mRNA of p38-MAPK, p53, and Bcl-2 [18]. Fig.…”

Section: Effects Of Hemorrhagic Shockmentioning

confidence: 97%

Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury

Kiang

2004

Cell Res

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Inducible heat shock protein 70 kD (HSP-70i) has been shown to protect cells, tissues, and organs from harmful assaults in in vivo and in vitro experimental models. Hemorrhagic shock followed by resuscitation is the principal cause of death among trauma patients and soldiers in the battlefield. Although the underlying mechanisms are still not fully understood, it has been shown that nitric oxide (NO) overproduction and inducible nitric oxide synthase (iNOS) overexpression play important roles in producing injury caused by hemorrhagic shock including increases in polymorphonuclear neutrophils (PMN) infiltration to injured tissues and leukotriene B 4 (LTB 4 ) generation. Moreover, transcription factors responsible for iNOS expression are also altered by hemorrhage and resuscitation. It has been evident that either up-regulation of HSP-70i or down-regulation of iNOS can limit tissue injury caused by ischemia/reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of ansamycin family, has been shown to induce HSP70i overexpression and then subsequently to inhibit iNOS expression, to reduce cellular caspase-3 activity, and to preserve cellular ATP levels. HSP-70i is found to couple to iNOS and its transcription factor. Therefore, the complex formation between HSP-70i and iNOS may be a novel mechanism for protection from hemorrhage/resuscitation-induced injury.

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The Use of Insulin and Glucose during Resuscitation from Hemorrhagic Shock Increases Hepatic ATP

Cited by 28 publications

References 28 publications

Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

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

Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury

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