The Role of Nitric Oxide in the Efficacy of Adenosine, Lidocaine, and Magnesium Treatment for Experimental Hemorrhagic Shock in Rats
| Autor: | Geoffrey P. Dobson, Hayley L. Letson |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Resuscitation
Mean arterial pressure endothelium Lidocaine medicine.medical_treatment resuscitation Hemodynamics RM1-950 Pharmacology Nitric oxide hemorrhagic shock chemistry.chemical_compound nitric oxide Medicine Pharmacology (medical) Saline Original Research nitric oxide synthase business.industry fungi Adenosine chemistry Shock (circulatory) Therapeutics. Pharmacology medicine.symptom business medicine.drug |
| Zdroj: | Current Therapeutic Research, Clinical and Experimental Current Therapeutic Research, Vol 95, Iss, Pp 100655-(2021) |
| ISSN: | 0011-393X |
| Popis: | Background: Nitric oxide (NO) plays multiple roles regulating the central nervous, cardiovascular, and immune systems. Objective: 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. Methods: 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. Results: 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. Conclusions: 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) |
| Databáze: | OpenAIRE |
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