ALM fluid therapy leads to 72 hr survival after hemorrhagic shock

Letson, Hayley Louise, Morris, Jodie Louise, Biros, Erik, and Dobson, Geoffrey Phillip (2019) ALM fluid therapy leads to 72 hr survival after hemorrhagic shock. Journal of Trauma and Acute Care Surgery. (In Press)

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BACKGROUND: Non-compressible torso hemorrhage is a leading cause of traumatic death. Our aim was to examine survival time and the expression of key master genes of cellular metabolism after 3% NaCl adenosine, lidocaine and Mg (ALM) bolus and 4hr 0.9% NaCl/ALM 'drip' in a rat model of uncontrolled hemorrhagic shock.

METHODS: Male Sprague-Dawley rats (425±8g) were anesthetized and randomly assigned to saline controls (n=10) or ALM therapy (n=10). Hemorrhage was induced by liver resection (60% left lateral lobe). After 15min, a single intravenous bolus of 3% NaCl ± ALM (0.7ml/kg) was administered (Phase 1), and after 60min, a 0.9% NaCl ± ALM stabilization 'drip' (0.5ml/kg/hour) was infused for 4hrs (Phase 2) with 72hr monitoring. Mean arterial pressure and lactate were measured. After 72hrs (or high moribund score), tissues were freeze-clamped and stored at -80°C. Total RNA was extracted in heart, brain and liver, and the relative expressions of amp-k, mitCO3, PGC-1α and sirt-1 genes were determined.

RESULTS: Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6±4.5hr and ALM animals 72±0hr (p<0.05). Death in controls was accompanied by ~7-fold increase in lactate, while ALM animals maintained lactates similar to baseline over 72hrs. The relative expression of amp-k, PGC-1α, and sirt-1 in heart and brain was 1.5- and 2.7-fold higher in the ALM group compared to controls (p<0.05), with the exception of mtCO3 in heart, which was 19-fold higher. In contrast, amp-k, sirt-1 and mitCO3 gene expression in liver was significantly 29-41% lower in the ALM group compared to controls, and PGC-1α was 75% lower.

CONCLUSIONS: Small-volume ALM therapy led to 3.3-times longer survival time compared to saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of amp-k, PGC-1α, sirt-1 and mitCO3 to presumably 'boost' mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.

LEVEL OF EVIDENCE: Randomized animal study.

Item ID: 58715
Item Type: Article (Research - C1)
ISSN: 2163-0763
Keywords: Noncompressible hemorrhage; ALM; survival; genetics; metabolism; far forward; hypotensive resuscitation
Copyright Information: © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Funders: US Department of Defense (DOD), James Cook University (JCU)
Date Deposited: 09 Jul 2019 04:06
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 80%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 20%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 80%
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