NHE1 inhibition improves tissue perfusion and resuscitation outcome after severe hemorrhage

Wu, Dongmei; Russano, Kristina; Kouz, Irene; Abraham, William M.

doi:10.1016/j.jss.2012.07.026

Cited by 11 publications

(16 citation statements)

References 24 publications

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“…This is illustrated by the results of 19 studies using different models characterized by tissue hypoxia and lactic acidosis published in the last 11 years. Models used included hypovolemic shock and volume resuscitation [8,15,16,17,18,19], hypoperfusion accompanied by lactic acid infusion [20], asphyxia with severe hypoxia [21], and severe trauma [17]. These studies have demonstrated that inhibition of NHE1 improves cardiac and neurological function, reduces blood and/or tissue concentrations of proinflammatory cytokines, and often strikingly reduces mortality [22,23].…”

Section: Hypoxic Lactic Acidosismentioning

confidence: 99%

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

Wu¹,

Kraut²

2014

Am J Nephrol

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Background: Metabolic acidosis is associated with impaired cellular function. This has been attributed to the accompanying reduction in intracellular and interstitial pH of the myocardium. Recent studies suggest that activation of the cellular Na⁺-H⁺ exchanger NHE1 might contribute to myocardial dysfunction. This review examines the experimental evidence which supports the role of NHE1 in the genesis of acidosis-induced cellular dysfunction, the benefits of its inhibition, and the type of acidosis that might benefit from therapy. Summary: Information was obtained by searching MEDLINE for articles published between 1969 and 2013 using the terms: NHE1, metabolic acidosis, lactic acidosis, ischemia-reperfusion, shock, resuscitation, high anion gap acidosis, and non-gap acidosis. Each article was also reviewed for additional suitable references. Nineteen manuscripts published between 2002 and 2013 assessed the impact of inhibition of NHE1 on cellular function. They revealed that NHE1 is activated with metabolic acidosis associated with hypoxia, hypoperfusion, hemorrhagic shock, and sepsis. This was associated with a rise in cellular sodium and calcium and cardiac dysfunction including reduced contractility and a predisposition to cardiac arrhythmias. Inhibition of NHE1 with specific inhibitors improved cardiac function, reduced blood and tissue levels of proinflammatory cytokines, and decreased mortality. Key Message: These results suggest that use of inhibitors of NHE1 might be worthwhile in the treatment of some types of acute metabolic acidosis, specifically the lactic acidosis associated with hypoxia, hemorrhagic shock, and cardiac arrest. Its potential role in the treatment of other forms of acute metabolic acidosis remains to be determined.

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Section: Hypoxic Lactic Acidosismentioning

confidence: 99%

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

Wu¹,

Kraut²

2014

Am J Nephrol

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“…Only animal experimental studies could be retrieved through the systematic literature search. Nine studies used pigs [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], five studies used rats [ 25 , 26 , 27 , 28 , 29 ], one study used dogs [ 30 ], and one study used cats [ 31 ]. The average number of animals used across the studies was 29.4 ± 12.4 (mean ± SD), the lowest number of utilised animals was 14 [ 22 ], and the highest was 60 [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Neuroprotective Strategies during Hypovolemia and Hemorrhagic Shock

Nistor

Behringer

Schmidt

et al. 2017

IJMS

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Severe trauma constitutes a major cause of death and disability, especially in younger patients. The cerebral autoregulatory capacity only protects the brain to a certain extent in states of hypovolemia; thereafter, neurological deficits and apoptosis occurs. We therefore set out to investigate neuroprotective strategies during haemorrhagic shock. This review was performed in accordance to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Before the start of the search, a review protocol was entered into the PROSPERO database. A systematic literature search of Pubmed, Web of Science and CENTRAL was performed in August 2017. Results were screened and evaluated by two researchers based on a previously prepared inclusion protocol. Risk of bias was determined by use of SYRCLE’s risk of bias tool. The retrieved results were qualitatively analysed. Of 9093 results, 119 were assessed in full-text form, 16 of them ultimately adhered to the inclusion criteria and were qualitatively analyzed. We identified three subsets of results: (1) hypothermia; (2) fluid therapy and/or vasopressors; and (3) other neuroprotective strategies (piracetam, NHE1-inhibition, aprotinin, human mesenchymal stem cells, remote ischemic preconditioning and sevoflurane). Overall, risk of bias according to SYRCLE’s tool was medium; generally, animal experimental models require more rigorous adherence to the reporting of bias-free study design (randomization, etc.). While the individual study results are promising, the retrieved neuroprotective strategies have to be evaluated within the current scientific context—by doing so, it becomes clear that specific promising neuroprotective strategies during states of haemorrhagic shock remain sparse. This important topic therefore requires more in-depth research.

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“…Resuscitation is recommended to be guided by several clinical aspect, such as vital signs, urine output, perfusion, acid-base imbalance, immune function, extracellular matrix production and cell chemotaxis, ability to prevent cerebral edema, pulmonary edema [ 15 ]. The most important factor at the cellular level is the exchange pump Na + /H + [ 31 ]. Wu et al, in a study conducted on a group of 24 pigs demonstrated that by blocking the pump Na + /H + and thus reducing the level of lactic acid could protect cellular alteration [ 31 ].…”

Section: Reviewmentioning

confidence: 99%

“…The most important factor at the cellular level is the exchange pump Na + /H + [ 31 ]. Wu et al, in a study conducted on a group of 24 pigs demonstrated that by blocking the pump Na + /H + and thus reducing the level of lactic acid could protect cellular alteration [ 31 ]. Ischemia and reperfusion is an important precursor in the inflammatory processes that are responsible for producing oxygenated reducing agents.…”

Section: Reviewmentioning

confidence: 99%

New perspectives of volemic resuscitation in polytrauma patients: a review

et al. 2016

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Nowadays, fluid resuscitation of multiple trauma patients is still a challenging therapy. Existing therapies for volume replacement in severe haemorrhagic shock can lead to adverse reactions that may be fatal for the patient. Patients presenting with multiple trauma often develop hemorrhagic shock, which triggers a series of metabolic, physiological and cellular dysfunction. These disorders combined, lead to complications that significantly decrease survival rate in this subset of patients. Volume and electrolyte resuscitation is challenging due to many factors that overlap. Poor management can lead to post-resuscitation systemic inflammation causing multiple organ failure and ultimately death. In literature, there is no exact formula for this purpose, and opinions are divided. This paper presents a review of modern techniques and current studies regarding the management of fluid resuscitation in trauma patients with hemorrhagic shock. According to the literature and from clinical experience, all aspects regarding post-resuscitation period need to be considered. Also, for every case in particular, emergency therapy management needs to be rigorously respected considering all physiological, biochemical and biological parameters.

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NHE1 inhibition improves tissue perfusion and resuscitation outcome after severe hemorrhage

Cited by 11 publications

References 24 publications

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

Role of NHE1 in the Cellular Dysfunction of Acute Metabolic Acidosis

A Systematic Review of Neuroprotective Strategies during Hypovolemia and Hemorrhagic Shock

New perspectives of volemic resuscitation in polytrauma patients: a review

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