Small-Volume 7.5% NaCl Adenosine, Lidocaine, and Mg2+ Has Multiple Benefits During Hypotensive and Blood Resuscitation in the Pig Following Severe Blood Loss

Granfeldt, Asger; Letson, Hayley L.; Hyldebrandt, Janus Adler; Wang, Edward R.; Salcedo, Pablo A.; Nielsen, Tommy Kjærgaard; Tønnesen, Else; Vinten‐Johansen, Jakob; Dobson, Geoffrey P.

doi:10.1097/ccm.0000000000000225

Cited by 36 publications

(38 citation statements)

References 36 publications

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“…22 One methodological difference that may influence coagulopathy is that we allow BT to drift in our rat and pig models, 35 which we believe is more clinically relevant in farforward military or prehospital environments. 22 One methodological difference that may influence coagulopathy is that we allow BT to drift in our rat and pig models, 35 which we believe is more clinically relevant in farforward military or prehospital environments.…”

Section: Bleeding and Shock Induced A Profound Hypocoagulopathymentioning

confidence: 99%

Correction of acute traumatic coagulopathy with small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ occurs within 5 minutes

Letson

Dobson

2015

Journal of Trauma and Acute Care Surgery

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Section: Bleeding and Shock Induced A Profound Hypocoagulopathymentioning

confidence: 99%

Correction of acute traumatic coagulopathy with small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ occurs within 5 minutes

Letson

Dobson

2015

Journal of Trauma and Acute Care Surgery

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“…Previous evidence suggests that supplemental energy production increases survival8910. Adenosine triphosphate (ATP), mainly synthesized in the mitochondria by the tricarboxylic acid (TCA) cycle, is an essential and direct source of energy for normal cardiac contraction, thus it is a promising indicator of heart failure and death11.…”

mentioning

confidence: 99%

Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

Kuai

Wang

et al. 2016

Sci Rep

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A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting.

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“…7 The ALM bolus and/or infusion treatments have been shown in rat and pig models to protect against regional myocardial ischemia, lethal arrhythmias, cardiac arrest, hemorrhagic shock, coagulopathy, inflammation, endotoxemia, infection and sepsis. [7][8][9][10][11][12] Adenosine, lidocaine and Mg 2+ alone do not confer these benefits. 7 In the present study, we hypothesized that the low-volume ALM drip/infusion may improve physiologic status in the first few hours following a single laparotomy.…”

Section: Introductionmentioning

confidence: 99%

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg²⁺ infusion to dampen the stress response

2017

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Our aim was to examine the effect of low-volume 0.9% NaCl adenosine, lidocaine and Mg 2+ (ALM) 'drip' on early immune-inflammatory activation after a single laparotomy with no further manipulation. Male Sprague-Dawley rats were anesthetized and randomly assigned to one of the groups, baseline, 1 h infusion 0.9% NaCl AE ALM and metrics, 1 h infusion and 6-h metrics, and 6 h continuous infusion and metrics. Complete blood count, acid-base balance, systemic levels of IL-6 and IL-10, and coagulation status were measured. After 1 h, there was a disproportionate increase in circulating neutrophils between saline and ALM groups despite an identical 45% fall in lymphocytes. Disproportionate increases also occurred in platelet counts 1 h after surgery, and saline controls had increased respiratory alkalosis at 6 h with higher lactate. Systemic inflammation was also evident after 1 h in both groups (plasma IL-6 increase) and was amplified in saline-controls after 6 h. The ALM group increased anti-inflammatory cytokine IL-10. Surgery was not associated with acute coagulopathy; however, there were significant reductions in fibrinolysis. Following a single laparotomy, ALM infusion appeared to reduce stress-induced release of neutrophils and platelets into the circulation, and reduced acid-base disturbance. After 1 h, both groups had similar IL-6 levels, but ALM animals had increased IL-10, indicating improved inflammatory balance. The uncoupling of inflammation and coagulation activation but not fibrinolysis may offer a unique opportunity to investigate differential activation of innate immunity in response to sterile injury in this model.

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Small-Volume 7.5% NaCl Adenosine, Lidocaine, and Mg2+ Has Multiple Benefits During Hypotensive and Blood Resuscitation in the Pig Following Severe Blood Loss

Abstract: Small-volume resuscitation with 7.5% NaCl + adenosine, lidocaine, and Mg/adenosine and lidocaine provided superior cardiovascular, acid-base, metabolic, and renal recoveries following severe hemorrhagic shock in the pig compared with 7.5% NaCl alone.

Cited by 36 publications

References 36 publications

Correction of acute traumatic coagulopathy with small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ occurs within 5 minutes

Correction of acute traumatic coagulopathy with small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ occurs within 5 minutes

Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg²⁺ infusion to dampen the stress response

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Small-Volume 7.5% NaCl Adenosine, Lidocaine, and Mg2+ Has Multiple Benefits During Hypotensive and Blood Resuscitation in the Pig Following Severe Blood Loss

Abstract: Small-volume resuscitation with 7.5% NaCl + adenosine, lidocaine, and Mg/adenosine and lidocaine provided superior cardiovascular, acid-base, metabolic, and renal recoveries following severe hemorrhagic shock in the pig compared with 7.5% NaCl alone.

Cited by 36 publications

References 36 publications

Correction of acute traumatic coagulopathy with small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ occurs within 5 minutes

Correction of acute traumatic coagulopathy with small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ occurs within 5 minutes

Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg2+ infusion to dampen the stress response

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Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg²⁺ infusion to dampen the stress response