Role of Nitric Oxide in Hemorrhagic Shock-Induced Bacterial Translocation

• Published in: The Journal of surgical research 2000-10, Vol.93 (2), p.247-256
• Main Authors: Hua, Teng Choo, Moochhala, Shabbir M.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Bacterial Translocation - physiology; Biological and medical sciences; Blood Pressure - drug effects; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; Enzyme Inhibitors - pharmacology; Guanidines - pharmacology; Intensive care medicine; Male; Medical sciences; NG-Nitroarginine Methyl Ester - pharmacology; nitrate/nitrite level; Nitrates - blood; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; nitric oxide synthase immunoreactivity; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitrites - blood; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic - microbiology; Shock, Hemorrhagic - pathology; Shock, Hemorrhagic - physiopathology; Survival Analysis; survival rate; Time Factors; tissue/organ damage
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.2000.5991

Background. Hemorrhagic shock-induced bacterial translocation is an etiologic factor in the pathogenesis of multiple system organ damage. Excessive production of nitric oxide (NO) during hemorrhagic shock may lead to cellular injury and gut barrier failure that promotes bacterial translocation. We investigated the effect of aminoguanidine (AG) and NG-nitro-l-arginine methyl ester (l-NAME), both inhibitors of NO synthase, on hemorrhagic shock- induced bacterial translocation in the rat. Materials and methods. Anesthetized male Sprague–Dawley rats were subjected to a hemorrhagic shock protocol for 30 min followed by intravenous injection (1 mL/kg body wt) with normal saline, AG (100 mg/kg), or l-NAME (10 mg/kg). Tissues/organs were examined histologically for damage and bacterial translocation. Plasma nitrate/nitrite was measured using a procedure based on the Griess reaction, and nitric oxide synthase (NOS) expression was determined immunohistochemically. Results. The shocked animals treated with saline died within 90 min, and deaths were associated with 100% bacterial translocation, increased tissue/organ damage, and elevated nitrate/nitrite production. In contrast, both AG and l-NAME increased the survival time of shocked rats to >72 h, abrogated bacterial translocation, reduced tissue/organ damage, and prevented excessive nitrate/nitrite production and upregulation of expression of endothelial NOS and inducible NOS. Conclusions. Prevention of bacterial translocation by pharmacologic agents such as aminoguanidine and l-NAME could be an important therapeutic approach to lessen mortality rates following hemorrhagic shock.