Combatting ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta using adenosine, lidocaine and magnesium: A pilot study

Conner, Jeff; Lammers, Daniel; Holtestaul, Torbjorg; Jones, Ian; Kuckelman, John; Letson, Hayley L.; Dobson, Geoffrey P.; Eckert, Matthew J.; Bingham, Jason

doi:10.1097/ta.0000000000003388

Cited by 9 publications

(6 citation statements)

References 35 publications

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“…A priori power analysis based on previous work by Conner et al 18 predicted that n = 15 per treatment group would provide a power of 0.8 using α of 0.05 19 . Animal experiments were concluded with a power of 0.86 being reached at n = 9 animals per group.…”

Section: Methodsmentioning

confidence: 99%

Adenosine, lidocaine, and magnesium for attenuating ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta in a porcine model

Franko

Parsons

et al. 2021

J Trauma Acute Care Surg

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BACKGROUND: Minimally invasive resuscitative endovascular balloon occlusion of the aorta (REBOA) following noncompressible hemorrhage results in significant ischemia reperfusion injury (IRI). Adverse outcomes from IRI include organ dysfunction and can result in profound hemodynamic and molecular compromise. We hypothesized that adenosine, lidocaine, and magnesium (ALM) attenuates organ injury and inflammation responses following REBOA IRI in a porcine model of hemorrhage. METHODS:Animals underwent a 20% controlled hemorrhage followed by 45 minutes of supraceliac balloon occlusion. They were randomized into two groups: control (n = 9) and ALM intervention (n = 9) to include a posthemorrhage, pre-REBOA bolus (200 mL of 3% NaCl ALM) followed by a continuous drip (2 mL/kg per hour of 0.9% NaCl ALM) during the 4-hour resuscitative period. Primary outcomes included hemodynamic parameters, gene expression of inflammatory signaling molecules, and plasma concentrations of select cytokines and chemokines. RESULTS:The ALM cohort demonstrated a significant reduction in cardiac output and cardiac index. Plasma concentrations of interleukin 2 and interleukin 10 were significantly lower 3 hours post-REBOA in animals treated with ALM versus vehicle. Interleukin 4 levels in plasma were also lower with ALM at 3 and 4 hours post-REBOA ( p < 0.05). Liver expression of IL1RN, MTOR, and LAMP3 messenger RNA was significantly lower with ALM as compared with the vehicle. No significant difference in large bowel gene expression was observed between treatments. CONCLUSION: In a porcine model of hemorrhage, ALM treatment mitigated inflammatory responses early during post-REBOA resuscitation. Our findings suggest that ALM use with trauma may reduce inflammatory injury and improve outcomes related to REBOA utilization.

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Section: Methodsmentioning

confidence: 99%

Adenosine, lidocaine, and magnesium for attenuating ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta in a porcine model

Franko

Parsons

et al. 2021

J Trauma Acute Care Surg

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“…Balloon inflation above the renal arteries can be used in hyper-acute care, but gut and renal ischemic injury occur quickly, limiting the length of time allowable. Gut resuscitation with adenosine, lidocaine, and magnesium after REBOA is under preclinical study [35 ▪ ]. Given the circumstances in which it is used, high-quality prospective trials are difficult to conduct [36 ▪ ].…”

Section: Balloons and Hemostatic Dressingsmentioning

confidence: 99%

Advances in hemorrhage control resuscitation

Muldowney

Aichholz

Nathwani

et al. 2022

Current Opinion in Anaesthesiology

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Purpose of reviewDespite significant advances in trauma management over the last twenty years, uncontrolled hemorrhage remains the leading cause of preventable death in trauma. We review recent changes affecting hemorrhage control resuscitation.Recent findingsEarly blood product usage has become well established as a standard of care in trauma hemorrhage control. To enable this, low titer group A liquid plasma and group O whole blood are increasingly utilized. Single donor apheresis platelets have now replaced pooled donor platelets in the USA and are often pathogen reduced, which has implications for trauma resuscitation. Further work is examining timing and dosing of tranexamic acid and the debate in factor concentrate usage in trauma induced coagulopathy continues to evolve. The ‘Stop the bleed’ campaign has highlighted how important the use of hemostatic dressings are in hemorrhage control, as too is the expanded use of endovascular aortic occlusion. We highlight the ongoing research into desmopressin use and the undetermined significance of ionized calcium levels in trauma. Finally, we discuss our own hospital experience with coagulation testing and the paucity of evidence of improved outcomes with viscoelastic testing.SummaryImproving trauma coagulopathy diagnostics and hemorrhage control are vital if we are to decrease the mortality associated with trauma.

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“…[6-8] At a low dose, ALM shows its protective effects in animal models of myocardial ischemia, arrhythmia, cardiac arrest, hemorrhagic shock, and septic shock [9]. The underlying mechanism could partly be explained by its ability to reduce in ammation, correct coagulopathy, and lower energy demands [10][11][12]. The protective effects of ALM on the cardiac system has been well elaborated [3].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of a Cardioplegic Combination (Adenosine, Lidocaine, and Magnesium) in an Ischemic Stroke Model

2022

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Adenosine, lidocaine, and magnesium (ALM) formula is a clinically available cardioplegic solution. We examined the effects of low dose ALM on ischemic stroke with cell and animal models. Cobalt chloride (CoCl 2 )-treated SH-SY5Y cells were used as our surrogate model to mimic oxygen-glucose deprivation condition. The cells were incubated with different dilutions of the ALM authentic solution (1.0 mM adenosine, 2.0 mM lidocaine, 5 mM MgSO4 in EBSS). At the concentration of 2.5%, ALM signi cantly reduce CoCl 2 -induced cell loss. The protective effect remained if ALM was given 1 hour within the insult.We then used transient middle cerebral artery occlusion to investigate the therapeutic effects of ALM in vivo. Rats were randomly assigned to two groups: the experimental (ALM) group vs. control (saline) group, and infusion was given during the ischemia for one hour. The infarction area was signi cantly reduced in the ALM group (5.0% ± 2.0% vs. 23.5%±5.5%, p=0.013). The neurological de cits was reduced in the ALM group (Modi ed Longa score: 0 [0-1] vs.2 [1-2], p=0.047). The neuroprotective effect was substantiated by the reduction of various neuron injury markers in the plasma. These results demonstrated the neuroprotective effects of ALM and may provide a new therapeutic strategy for ischemic stroke.

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Combatting ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta using adenosine, lidocaine and magnesium: A pilot study

Cited by 9 publications

References 35 publications

Adenosine, lidocaine, and magnesium for attenuating ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta in a porcine model

Adenosine, lidocaine, and magnesium for attenuating ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta in a porcine model

Advances in hemorrhage control resuscitation

Neuroprotective Effects of a Cardioplegic Combination (Adenosine, Lidocaine, and Magnesium) in an Ischemic Stroke Model

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