Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock

Ba, Zheng F.; Wang, Haichao; Koo, Douglas J.; Cioffi, William G.; Bland, Kirby I.; Chaudry, Irshad H.

doi:10.1097/00003246-200008000-00026

Cited by 81 publications

(62 citation statements)

References 26 publications

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“…Although hyperkalemia and hyponatremia developed in the DHS and SHS groups, electrolytes normalized with resuscitation. As previously described, this model of hemorrhagic shock was associated with a significant decrease in hemoglobin in the DHS and SHS groups that further declined in the R group (18). …”

Section: Resultssupporting

confidence: 64%

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Karamercan¹,

Weiss²,

Villarroel

et al. 2013

Shock

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INTRODUCTION Although mitochondrial dysfunction is thought to contribute to the development of post-traumatic organ failure, current techniques to assess mitochondrial function in tissues are invasive and clinically impractical. We hypothesized that mitochondrial function in peripheral blood mononuclear cells (PBMCs) would reflect cellular respiration in other organs during hemorrhagic shock and resuscitation (HS&R). METHODS Using a fixed pressure HS model, Long Evan’s rats were bled to a mean arterial pressure (MAP) of 40 mmHg. When blood pressure could no longer be sustained without intermittent fluid infusion (Decompensated HS), Lactated Ringer’s (LR) was incrementally infused to maintain the MAP at 40 mmHg until 40% of the shed blood volume was returned (Severe HS). Animals were then resuscitated with 4X total shed volume in LR over 60 minutes (Resuscitation). Control animals underwent the same surgical procedures, but were not hemorrhaged. Animals were randomized to Control (n=6), Decompensated HS (n=6), Severe HS (n=6) or Resuscitation (n=6) groups. Kidney, liver, and heart tissues as well as PBMC’s were harvested from animals in each group to measure mitochondrial oxygen consumption using high resolution respirometry. Flow cytometry was used to assess mitochondrial membrane potential (Ψm) in PBMCs. One-way ANOVA and Pearson correlations were performed. RESULTS Mitochondrial oxygen consumption decreased in all tissues, including PBMC’s, following Decompensated HS, Severe HS, and Resuscitation. However, the degree of impairment varied significantly across tissues during HS&R. Of the tissues investigated, PBMC mitochondrial oxygen consumption and Ψm provided the closest correlation to kidney mitochondrial function during HS (complex I: r =0.65; complex II: r=0.65; complex IV: r=0.52; p<0.05). This association, however, disappeared with resuscitation. A weaker association between PBMC and heart mitochondrial function was observed but no association was noted between PBMC and liver mitochondrial function. CONCLUSION All tissues including PBMC’s demonstrated significant mitochondrial dysfunction following HS&R. Although PBMC and kidney mitochondrial function correlated well during hemorrhagic shock, the variability in mitochondrial response across tissues over the spectrum of hemorrhagic shock and resuscitation limits the usefulness of using PBMC’s as a proxy for tissue-specific cellular respiration.

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Section: Resultssupporting

confidence: 64%

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Karamercan¹,

Weiss²,

Villarroel

et al. 2013

Shock

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show abstract

“…It has been shown that cardiac output, left ventricular performance and organ blood flow in the liver, small intestine and kidney decreased significantly following T-H and resuscitation (6,7). A prolonged depression of cardiovascular function following T-H, despite fluid resuscitation was also reported by other investigators (8)(9)(10).…”

Section: Introductionmentioning

confidence: 61%

“…This procedure was performed as described earlier (6). For surgery, the rats were fasted for 16 h prior to the procedure but allowed water ad libitum, anesthetized with isoflurane (Minrad, Bethlehem, PA, USA) and restrained in a supine position.…”

Section: Trauma-hemorrhage Proceduresmentioning

confidence: 99%

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

Jian

Yang

Chen

et al. 2010

Mol Med

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Cardiac dysfunction and mortality associated with trauma and sepsis increase with age. Mitochondria play a critical role in the energy demand of cardiac muscles, and thereby on the function of the heart. Specific molecular pathways responsible for mitochondrial functional alterations after injury in relation to aging are largely unknown. To further investigate this, 6-and 22-monthold rats were subjected to trauma-hemorrhage (T-H) or sham operation and euthanized following resuscitation. Left ventricular tissue was profiled using our custom rodent mitochondrial gene chip (RoMitochip). Our experiments demonstrated a declined left ventricular performance and decreased alteration in mitochondrial gene expression with age following T-H and we have identified c-Myc, a pleotropic transcription factor, to be the most upregulated gene in 6-and 22-month-old rats after T-H. Following T-H, while 142 probe sets were altered significantly (39 up and 103 down) in 6-month-old rats, only 66 were altered (30 up and 36 down) in 22-month-old rats; 36 probe sets (11 up and 25 down) showed the same trend in both groups. The expression of c-Myc and cardiac death promoting gene Bnip3 were increased, and Pgc1-α and Ppar-α a decreased following T-H. Eleven tRNA transcripts on mtDNA were upregulated following T-H in the aged animals, compared with the sham group. Our observations suggest a cmyc-regulated mitochondrial dysfunction following T-H injury and marked decrease in age-dependent changes in the transcriptional profile of mitochondrial genes following T-H, possibly indicating cellular senescence. To our knowledge, this is the first report on mitochondrial gene expression profile following T-H in relation to aging.

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“…Rats were subjected to hemorrhage or sham operation as described earlier (5). The rats fasted overnight (water allowed ad lib) and then were anesthetized with isoflurane (Minrad, Bethlehem, PA, USA) and restrained in a supine position, before surgery.…”

Section: Hemorrhage Proceduresmentioning

confidence: 99%

“…Hemorrhagic shock also causes decreased cardiac output, stroke volume and cardiac contractility (±dP/dt) (1)(2)(3). Hypoxia and reperfusion injury result in dysregulation of critical molecular pathways and bioprocesses (4)(5)(6)(7)(8)(9). The predominant causes for mortality following hemorrhagic shock are sepsis and multiple organ failure (10).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1

Jian

Yang

Chaudry

et al. 2011

Mol Med

Self Cite

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Mitochondria play a critical role in metabolic homeostasis of a cell. Our recent studies, based on the reported interrelationship between c-Myc and Sirt1 (mammalian orthologue of yeast sir2 [silent information regulator 2]) expression and their role in mitochondrial biogenesis and function, demonstrated a significant downregulation of Sirt1 protein expression and an upregulation of c-Myc following trauma-hemorrhage (T-H). Activators of Sirt1 are known to improve mitochondrial function and the naturally occurring polyphenol resveratrol (RSV) has been shown to significantly increase Sirt1 activity by increasing its affinity to both NAD+ and the acetylated substrate. In this study we tested the salutary effect of RSV following T-H and its influence on Sirt1 expression. Rats were subjected to T-H or sham operation. RSV (8 mg/kg body weight, intravenously) or vehicle was administered 10 min after the onset of resuscitation, and the rats were killed 2 h following resuscitation. Sirtinol, a Sirt1 inhibitor, was administered 5 min prior to RSV administration. Cardiac contractility (±dP/dt) was measured and heart tissue was tested for Sirt1, Pgc-1α, c-Myc, cytosolic cytochrome C expression and ATP level. Left ventricular function, after T-H, was improved (P < 0.05) following RSV treatment, with significantly elevated expression of Sirt1 (P < 0.05) and Pgc-1α (P < 0.05), and decreased c-Myc (P < 0.05). We also observed significantly higher cardiac ATP content, declined cytosolic cytochrome C and decreased plasma tumor necrosis factor-α in the T-H-RSV group. The salutary effect due to RSV was abolished by sirtinol, indicating a Sirt1-mediated effect. We conclude that RSV may be a useful adjunct to resuscitation fluid following T-H.

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Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock

Abstract: Because the liver experienced the most severe reduction in VO2 associated with an unchanged oxygen extraction capacity, this organ appears to be more vulnerable to hypoxic insult after hemorrhagic shock.

Cited by 81 publications

References 26 publications

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1

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