Intravenous pyruvate prolongs survival  during hemorrhagic shock in swine

Mongan, Paul D.; Fontana, John L.; Chen, Rouyan; Bünger, Rolf

doi:10.1152/ajpheart.1999.277.6.h2253

Cited by 46 publications

(67 citation statements)

References 27 publications

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“…Finally, the model provides a means to explore new therapeutic strategies and pharmacology. It has been reported in animal studies that pyruvate may prolong neural survival during ischemic infarctions (48,49). Pyruvate is known to stabilize oxidative metabolism by increasing ATP production during hypoxic events.…”

Section: Discussionmentioning

confidence: 99%

A neurophysiological–metabolic model for burst suppression

Ching

Purdon

Vijayan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

259

326

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Burst suppression is an electroencepholagram (EEG) pattern in which high-voltage activity alternates with isoelectric quiescence. It is characteristic of an inactivated brain and is commonly observed at deep levels of general anesthesia, hypothermia, and in pathological conditions such as coma and early infantile encephalopathy. We propose a unifying mechanism for burst suppression that accounts for all of these conditions. By constructing a biophysical computational model, we show how the prevailing features of burst suppression may arise through the interaction between neuronal dynamics and brain metabolism. In each condition, the model suggests that a decrease in cerebral metabolic rate, coupled with the stabilizing properties of ATP-gated potassium channels, leads to the characteristic epochs of suppression. Consequently, the model makes a number of specific predictions of experimental and clinical relevance.B urst suppression-an electroencephalogram (EEG) pattern in which high voltage activity (burst) and flatline (suppression) periods alternate systematically but quasiperiodically (almost periodic but with variations in inter-and intra-burst duration) (1)-is a state of profound brain inactivation. It is frequently observed in deep general anesthesia (2). It is also observed in a range of pathological conditions including hypothermia (3-5), hypoxic-ischemic trauma/coma (6), and the so-called Ohtahara syndrome (7,8), a type of early infantile encephalopathy. These etiologies indicate that the burst suppression pattern represents a low-order dynamic mechanism that persists in the absence of higher-level brain activity. Indeed, the fact that many different conditions produce similar brain activity suggests that there may be a common pathway to the state of brain inactivation and may indicate fundamental properties of the brain's arousal circuits (2).The basic features of the burst suppression phenomenon have been established through a variety of EEG studies that are reviewed in ref. 9. The two most notable of these features are the spatial homogeneity of bursts and the quasi-periodic nature of the suppression. Later research has been directed at describing the phenomenon in vivo and in the specific context of general anesthesia. In particular, the early work of Steriade et al. (10) helped establish the neural correlates of burst suppression, including the differential participation of cortical and subcortical cell types. More recent studies (11,12) have suggested that burst suppression is associated with enhanced excitability in cortical networks. These studies implicate extracellular calcium as a correlate for the switches between burst and suppression.Despite the findings of these studies, a unifying mechanism for burst suppression-one that explains its prevailing features and also accounts for its range of etiologies-has not been proposed. Indeed, the existing characterizations of burst suppression in pathological situations are highly limited. Computational models offer a means of synthesizing the availabl...

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Section: Discussionmentioning

confidence: 99%

A neurophysiological–metabolic model for burst suppression

Ching

Purdon

Vijayan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

259

326

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“…First, EP may function as a metabolic substrate to decrease the cytosolic NADH/NADϩ ratio and maintain the cellular phosphorylation potential ATP/ADP-Pi; this mechanism has been proposed to explain some of the beneficial effects of the parent compound pyruvate. 19 Second, EP may function as an effective scavenger of ROS, as does pyruvate. 20 Regarding this issue, we found that EP exerts a protective effect on a primary cortical culture when it is exposed to oxidative stress (Kim et al, unpublished data, 2005).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the Cerebral Ischemic Injury by Ethyl Pyruvate With a Wide Therapeutic Window

Kim

Lee

et al. 2005

Stroke

121

110

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Background and Purpose-Ethyl pyruvate (EP) is a pyruvate derivative that has been reported recently to prevent lethality in mice with established lethal sepsis and systemic inflammation. In this study, we examined the neuroprotective effect of EP in a rat cerebral ischemia model of middle cerebral artery occlusion (MCAO). Methods-Male Sprague-Dawley rats were subjected to 1 hour of MCAO, and EP was administered at various time points before or after MCAO. The changes in the brain infarction, neurological deficits, microglia activation, and proinflammatory cytokine expression were evaluated. BV2 microglial cells were also used to access the anti-inflammatory effect of EP.

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“…In 1991, Salahudeen et al (39) reported that intravenous infusion of sodium pyruvate protects rats from renal parenchymal injury induced by injecting H 2 O 2 into the renal artery. After the publication of that paper, a number of other investigators reported that treatment with pyruvate could protect animals from the deleterious effects of a variety of conditions thought to be mediated by ROS, including myocardial I/R (4,7,8,11,35), intestinal I/R (6), and HS/R (30).…”

Section: Discussionmentioning

confidence: 99%

Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock

Yang¹,

Gallo²,

Baust³

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

155

143

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Administration of pyruvate, an effective scavenger of reactive oxygen species, has been shown to be salutary in numerous models of redox-mediated tissue or organ injury. Pyruvate, however, is unstable in solution and, hence, is not attractive for development as a therapeutic agent. Herein, ethyl pyruvate, which is thought to be more stable than the parent compound, was formulated in a calcium-containing balanced salt solution [Ringer ethyl pyruvate solution (REPS)] and evaluated in a murine model of hemorrhagic shock and resuscitation (HS/R). Resuscitation with REPS instead of Ringer lactate solution (RLS) significantly improved survival at 24 h and abrogated bacterial translocation to mesenteric lymph nodes and the development of increased ileal mucosal permeability to FITC-labeled dextran (4,000 Da) at 4 h. Mice treated with REPS instead of RLS also had lower circulating levels of alanine aminotransferase at 4 h. Treatment with REPS instead of RLS decreased activation of nuclear factor-κB in liver and colonic mucosa after HS/R and also decreased the expression of inducible nitric oxide synthase, tumor necrosis factor, cyclooxygenase-2, and interleukin-6 mRNA in liver, ileal mucosa, and/or colonic mucosa. These data support the view that resuscitation with REPS modulates the inflammatory response and decreases hepatocellular and gut mucosal injury in mice subjected to HS/R.

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Intravenous pyruvate prolongs survival during hemorrhagic shock in swine

Cited by 46 publications

References 27 publications

A neurophysiological–metabolic model for burst suppression

A neurophysiological–metabolic model for burst suppression

Inhibition of the Cerebral Ischemic Injury by Ethyl Pyruvate With a Wide Therapeutic Window

Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock

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