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              TABLE 4  Summary of Baseline Plasma Levels of α -Acid Glycoprotein (*AGP) (also called Orosomucoid) in Mouse, Rat, Pig and Human.

                Adult Species  μg/mL   Relative to Human              Comment                      Reference
              Mouse            100          ~20%        ➝   20 times during acute phase activation  Smith and Waters (2019) 43
              Sprague-Dawley  230–320       48%         ➝   up to 10 times during surgery, stress, injury, and   Smith and Waters (2019) 43
              rat              (275)                  inflammation
              Pig           1,000–3,000  3.5-fold higher  Strongly age dependent. Newborn basal levels 2–6   Heegaard et al. (2013) 42
                              (2,000)                 times  ➝   than adults. Adult AGP   after infection and
                                                                             ➝
                                                      opposite to other species.
              Human          390–740         —          ➝   2–4 times during heart attack, major surgery,   Smith and Waters (2019) 43
                               (565)                  burns, and trauma
              *AGP, an important constituent of human and animal plasma, is a major positive acute-phase protein (except pigs) with drug-binding, anti-in-
              flammatory, and immunomodulatory properties. AGP can bind >300 drugs.



              forward use of blood products (i.e., person-to-person, prehos-  6.  Eastridge BJ, Mabry RL, Seguin P, et al. Death on the battlefield
              pital blood banking, freeze-dried plasma/ and platelets) and   (2001–2011): implications for the future of combat casualty care.
              may have a broad-spectrum public purpose for prehospital ci-  J Trauma Acute Care Surg. 2012;73(6 suppl 5):S431–437.
              vilian trauma and aeromedical retrieval. Notwithstanding our   7.  Cap AP, Pidcoke HF, DePasquale M, et al. Blood far forward:
              progress in ALM development, it is important to emphasize   Time to get moving! J Trauma Acute Care Surg. 2015;78(6 suppl
                                                                    1):S2–S6.
              that more ALM translational studies and trials are required   8.  Dobson GP.  On being  the right  size:  heart design,  mitochon-
              before safe field use is possible.                    drial efficiency, and lifespan potential. Clin Exp Pharm Physiol.
                                                                    2003;30(8):590–597.
              Acknowledgments                                    9.  Dobson GP. Organ arrest, protection and preservation: natural
              The authors would particularly like to thank the US Depart-  hibernation to cardiac surgery: a review. Comp Biochem Physiol
                                                                    Part B. 2004;139:469–485.
              ment of Defense for their continued support of our work   10.  Dobson GP, Letson HL. Adenosine, lidocaine and Mg  (ALM):
                                                                                                          2+
              and the College of Medicine and Dentistry at James Cook   from cardiac surgery to combat casualty care: teaching old drugs
              University.                                           new tricks. J Trauma Acute Care Surg. 2016;80(1):135–145.
                                                                 11.  Dobson GP, Faggian G, Onorati F, et al.. Hyperkalemic cardio-
              Author Contributions                                  plegia in adult and pediatric cardiac surgery: end of an era? Front
              G.P.D. and H.L.L. contributed equally to literature search,   Clin Transl Physiol. 2013;4(Aug 28):1–28.
              study design, data interpretation, and writing of the manuscript.  12.  Dobson GP, Jones MW. Adenosine and lignocaine: a new concept
                                                                    in non-depolarising surgical arrest, protection and preservation. J
                                                                    Thorac Cardiovasc Surg. 2004;127(3):794–805.
              Conflict of Interest Statement                     13.  Dobson GP. Membrane polarity: a target for myocardial pro-
              G.P.D. is the sole inventor of the ALM concept for cardiac sur-  tection and reduced inflammation in adult and pediatric car-
              gery, trauma, sepsis, and cardioplegia. H.L.L. has no conflicts   diothoracic surgery (Editorial).  J Thorac Cardiovasc Surg.
              to declare.                                           2010;140(December):1213–1217.
                                                                 14.  Onorati F, Santini F, Dandale R, et al. “Polarizing” microplegia
                                                                    improves cardiac cycle efficiency after CABG for unstable angina.
              Funding                                               Int J Cardiol. 2013;167(6):2739–2746.
              This work was supported by USSOCOM, IACUC protocol   15.  Onorati F, Dobson GP, San Biagio L, et al. Superior myocardial
              A2118 and A2296, USAMRMC proposal SO150053 under      protection using ‘polarizing’ adenosine, lidocaine, and Mg
                                                                                                                2+
              Award No. W81XWH-USSOCOM-BAA-15-1. The opinions,      (ALM) cardioplegia in humans. J Am Coll Cardiol. 2016;67(14):
              interpretations, and conclusions are those of the authors and   1751–1753.
                                                                                                                2+
              are not necessarily endorsed by the US Department of Defense.  16.  Letson HL, Dobson GP. Ultra-small IV bolus of 7.5% NaCl/Mg
                                                                    with adenosine and lidocaine (ALM) improves early resuscitation
                                                                    outcome in the rat following severe hemorrhagic shock in vivo. J
              Availability of Data and Materials                    Trauma. 2011;71(3):708–719.
              The datasets supporting the conclusions of this manuscript   17.  Letson HL, Dobson GP. Small-volume 7.5% NaCl with 6% dex-
              can be made available by emailing the authors.        tran-70 or 6% and 10% Hetastarch are associated with arrhyth-
                                                                    mias and death following 60 min of severe hemorrhagic shock in
                                                                    the rat in vivo. J Trauma. 2011;70(June 6):1444–1452.
              References                                         18.  Canyon SJ, Dobson GP. Protection against ventricular arrhyth-
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