Adenosine, lidocaine, and Mg2+ (ALM): from cardiac surgery to combat casualty care - teaching old drugs new tricks

Dobson, Geoffrey Phillip, and Letson, Hayley Louise (2016) Adenosine, lidocaine, and Mg2+ (ALM): from cardiac surgery to combat casualty care - teaching old drugs new tricks. Journal of Trauma and Acute Care Surgery, 80 (1). pp. 135-145.

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Abstract

New frontline drugs and therapies are urgently required to protect the body from primary and secondary injuries. We review more than 10 years of work on adenosine, lidocaine, and magnesium (ALM) and its possible significance to civilian and military medicine. Adenosine is an endogenous nucleoside involved in nucleotide production, adenosine triphosphate turnover, and restoration of supply and demand imbalances. Lidocaine is a local anesthetic and Class 1B antiarrhythmic, and magnesium is essential for ionic regulation and cellular bioenergetics. Individually, each plays important roles in metabolism, immunomodulation, inflammation, and coagulation. The original idea to combine all three was as a polarizing cardioplegia, an idea borrowed from natural hibernators. Two recent prospective, randomized human trials have demonstrated its safety and superiority in myocardial protection over high-potassium depolarizing solutions. The next idea came from witnessing how the human heart spontaneously reanimated after complex operations with little inotropic support. At high doses, ALM arrests the heart, and at lower doses, it resuscitates the heart. In rat and pig models, we have shown that ALM intravenous bolus and infusion drip protects against acute regional myocardial ischemia, lethal arrhythmias, cardiac arrest, compressible and noncompressible blood loss and shock, endotoxemia, and sepsis. Individually, adenosine, lidocaine, or magnesium fails to protect. Protection is afforded in part by reducing inflammation, correcting coagulopathy, and lowering energy demand. We propose a unifying hypothesis involving improved central, cardiovascular and endothelium coupling to maintain sufficient tissue oxygenation and reduce primary and secondary hit complications. As with any new drug innovation, translation into humans is challenging.

Item ID: 42402
Item Type: Article (Research - C1)
ISSN: 2163-0763
Keywords: hemorrhage, trauma, injury, shock, inflammation
Funders: Australian Health Foundation, Australian Research Council (ARC), National Health and Medical Research Council of Australia (NHMRC), US Navy Medical Development Program, James Cook University
Date Deposited: 03 Feb 2016 14:52
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110305 Emergency Medicine @ 10%
11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 40%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 60%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 40%
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