The role of nitric oxide in the efficacy of adenosine, lidocaine and magnesium (ALM) treatment of experimental hemorrhagic shock in rats

Letson, Hayley L., and Dobson, Geoffrey P. (2021) The role of nitric oxide in the efficacy of adenosine, lidocaine and magnesium (ALM) treatment of experimental hemorrhagic shock in rats. Current Therapeutic Research, 95. 100655.

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Background: Since nitric oxide (NO) plays multiple roles regulating the central nervous, cardiovascular and immune systems, our aim was to investigate the role of NO in the efficacy of 7.5% NaCl adenosine, lidocaine and magnesium (ALM) to improve mean arterial pressure (MAP) and heart rate (HR) following hemorrhagic shock (HS).

Methods: Male Sprague-Dawley rats (101; 425±6g) were randomly assigned to 20 groups (n=4-n=8). HS (MAP<40mmHg) was induced by 20min pressure-controlled bleeding (∼40% blood volume), and the animal was left in shock (MAP 35-40mmHg) for 60min. NO synthase (NOS) inhibitor L-NAME was administered with a 0.3ml bolus of different combinations of 7.5% NaCl ALM active ingredients and hemodynamics were monitored for 60min. A number of specific NOS and NO inhibitors were tested.

Results: 7.5% NaCl ALM corrected MAP after HS. In contrast, the addition of L-NAME to 7.5% NaCl ALM led to a rapid fall in MAP, sustained ventricular arrhythmias, and 100% mortality. Saline controls receiving 7.5% NaCl with L-NAME showed improved MAP with no deaths. None of the specific NOS and NO inhibitors mimicked L-NAME's effect on ALM. The addition of inducible (iNOS) inhibitor 1400W to 7.5% NaCl ALM failed to resuscitate, while NO scavenger PTIO and PI3K inhibitor Wortmannin reduced MAP recovery during 60min resuscitation.

Conclusions: The ability of 7.5% NaCl ALM to resuscitate appears to be linked to one or more NO-producing pathways. Non-specific NOS inhibition with L-NAME blocked ALM resuscitation and led to cardiovascular collapse. More studies are required to examine NO site-specific contributions to ALM resuscitation.

Item ID: 70984
Item Type: Article (Research - C1)
ISSN: 1879-0313
Keywords: hemorrhagic shock; nitric oxide; resuscitation; nitric oxide synthase; endothelium
Copyright Information: © 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. (
Date Deposited: 01 Dec 2021 03:55
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320207 Emergency medicine @ 40%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3208 Medical physiology > 320803 Systems physiology @ 40%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 20%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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