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• W3215630364 startingPage "100655" @default.
• W3215630364 abstract "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 hypertonic saline (7.5% sodium chloride [NaCl]) adenosine, lidocaine, and magnesium (ALM) to improve mean arterial pressure (MAP) and heart rate following hemorrhagic shock. One hundred one male Sprague-Dawley rats (mean [SD] weight = 425 [6] g) were randomly assigned to 20 groups (groups of 4–8 rats each). Hemorrhagic shock (MAP < 40 mm Hg) was induced by 20-minute pressure-controlled bleeding (∼40% blood volume), and the animal was left in shock (MAP = 35-40 mm Hg) for 60 minutes. The NO synthase (NOS) inhibitor L-NAME was administered with a 0.3-mL bolus of different combinations of 7.5% NaCl ALM active ingredients and hemodynamic parameters were monitored for 60 minutes. A number of specific NOS and NO inhibitors were tested. We found that 7.5% NaCl ALM corrected MAP after hemorrhagic shock. 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 NG-nitro-l-arginine methyl ester (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 NOS inhibitor 1400W to 7.5% NaCl ALM failed to resuscitate, whereas the NO scavenger PTIO and the PI3K inhibitor wortmannin reduced MAP recovery during 60-minute resuscitation. The ability of 7.5% NaCl ALM to resuscitate appears to be linked to 1 or more NO-producing pathways. Nonspecific 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. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX)" @default.
• W3215630364 created "2021-12-06" @default.
• W3215630364 creator A5014268293 @default.
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• W3215630364 date "2021-01-01" @default.
• W3215630364 modified "2023-10-03" @default.
• W3215630364 title "The Role of Nitric Oxide in the Efficacy of Adenosine, Lidocaine, and Magnesium Treatment for Experimental Hemorrhagic Shock in Rats" @default.
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• W3215630364 doi "https://doi.org/10.1016/j.curtheres.2021.100655" @default.
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