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10.1097/TA.0000000000002397

http://scihub22266oqcxt.onion/10.1097/TA.0000000000002397
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31162330!ä!31162330

suck abstract from ncbi


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pmid31162330      J+Trauma+Acute+Care+Surg 2019 ; 87 (3): 606-613
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  • Adenosine, lidocaine, and Mg2+ fluid therapy leads to 72-hour survival after hemorrhagic shock: A model for studying differential gene expression and extending biological time #MMPMID31162330
  • Letson HL; Morris JL; Biros E; Dobson GP
  • J Trauma Acute Care Surg 2019[Sep]; 87 (3): 606-613 PMID31162330show ga
  • BACKGROUND: Noncompressible 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 4 hours 0.9% NaCl/ALM "drip" in a rat model of uncontrolled hemorrhagic shock. METHODS: Male Sprague-Dawley rats (425 +/- 8 g) 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 15 minutes, a single intravenous bolus of 3% NaCl +/- ALM (0.7 mL/kg) was administered (Phase 1), and after 60 minutes, a 0.9% NaCl +/- ALM stabilization "drip" (0.5 mL/kg per hour) was infused for 4 hours (Phase 2) with 72 hours monitoring. Mean arterial pressure and lactate were measured. After 72 hours (or high moribund score), tissues were freeze-clamped and stored at -80 degrees C. Total RNA was extracted in heart, brain, and liver, and the relative expressions of amp-k, mtCO3, PGC-1alpha, and sirt-1 genes were determined. RESULTS: Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6 +/- 4.5 hours, and ALM animals, 72 +/- 0 hours (p < 0.05). Death in controls was accompanied by approximately sevenfold increase in lactate, while ALM animals maintained lactates similar to baseline over 72 hours. The relative expression of amp-k, PGC-1alpha, and sirt-1 in heart and brain was 1.5-fold and 2.7-fold higher in the ALM group compared with controls (p < 0.05), with the exception of mitochondrial encoded cytochrome C oxidase III pseudogene 1 in heart, which was 19-fold higher. In contrast, amp-k, sirt-1, and mtCO3 gene expression in liver was significantly 29-41% lower in the ALM group compared with controls, and PGC-1alpha was 75% lower. CONCLUSION: Small-volume ALM therapy led to 3.3-times longer survival time compared with saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of amp-k, PGC-1alpha, sirt-1, and mtCO3 to presumably "boost" mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.
  • |Adenosine/administration & dosage/*therapeutic use[MESH]
  • |Animals[MESH]
  • |Disease Models, Animal[MESH]
  • |Fluid Therapy/*methods[MESH]
  • |Gene Expression Profiling[MESH]
  • |Gene Expression/drug effects[MESH]
  • |Lidocaine/administration & dosage/*therapeutic use[MESH]
  • |Magnesium/administration & dosage/*therapeutic use[MESH]
  • |Male[MESH]
  • |Rats[MESH]
  • |Rats, Sprague-Dawley[MESH]
  • |Real-Time Polymerase Chain Reaction[MESH]
  • |Shock, Hemorrhagic/drug therapy/metabolism/mortality/*therapy[MESH]


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