Neuronal nitric oxide inhibition attenuates the protective effect of HBO2 during cyanide poisoning.

PURPOSE: Experiments have shown that hyperbaric oxygen (HBO2) therapy reduces cyanide-induced cerebral distress. The exact mechanism behind HBO2's neuroprotective effect is unknown, but has been proposed to be mediated by an increased neuronal nitric oxide (NO) bioavailability, which may compete with cyanide for the active site of cytochrome oxidase in the mitochondrial respiratory chain. We hypothesized that the ameliorating effect of HBO2 is caused by an increased bioavailability of NO, which can be attenuated by injection of the selective neuronal NO synthase inhibitor, 7-nitroindazole, preceding the HBO2 procedure. METHODS: A total of 41 anesthetized female Sprague-Dawley rats were allocated to four groups: 1) vehicle [1.2 ml isotonic NaCl via intra-arterial administration]; 2) cyanide [5.4 mg/kg potassium CN (KCN) intra-arterial] plus 7-nitroindazole [25 mg/kg 7-nitroindazole via intraperitoneal injection]; 3) cyanide plus 7-nitroindazole plus HBO2 [284 kPa for 90 minutes]; 4) cyanide plus 7-nitroindazole plus normobaric oxygen [101.3 kPa for 90 minutes]. Cerebral interstitial lactate, glucose, glycerol and pyruvate were evaluated by means of microdialysis. RESULTS: HBO2 during inhibition of nNOS worsened cerebral metabolism compared to both solely CN-intoxicated animals and normobaric oxygen-treated animals. This was indicated by elevated lactate (in mM; 0.85 vs. 0.63 and 0.42, P=0.006 and P ⟨ 0.001, respectively), glycerol (in mM; 46 vs. 17 and 14, both P ⟨ 0.001), glucose (in mM; 0.58 vs. 0.31 and 0.32, both P ⟨ 0.001). CONCLUSIONS: The results indicate that a specific nNOS inhibition offsets the ameliorating effect of HBO2 during cerebral CN intoxication. However, other factors might contribute to this neuroprotective effect as well.

How biomarkers reflect the prognosis and treatment of necrotising soft tissue infections and the effects of hyperbaric oxygen therapy: the protocol of the prospective cohort PROTREAT study conducted at a tertiary hospital in Copenhagen, Denmark.

INTRODUCTION: Not enough is known regarding the prognosis and treatment of necrotising soft tissue infections (NSTIs). Mortality has been shown to be 25%-35%, with survivors coping with amputations and prolonged rehabilitation. This study will evaluate soluble urokinase-type plasminogen activator receptor (suPAR) as a possible prognostic marker of NSTI severity and mortality, as well as whether hyperbaric oxygen therapy (HBOT) can modulate markers of endothelial damage during NSTI. We hypothesise that in patients with NSTI, suPAR can provide prognostic risk assessment on hospital admission and that HBOT can reduce the endothelial damage that these patients are exposed to. METHODS AND ANALYSIS: This is a prospective observational study. Biomarkers will be measured in 150 patients who have been diagnosed with NSTI. On admission, baseline blood samples will be obtained. Following surgery and HBOT, daily blood samples will be obtained in order to measure endothelial and prognostic biomarkers (soluble thrombomodulin, syndecan-1, sE-selectin, vascular endothelial (VE)-cadherin, protein C and suPAR levels). Clinical data will be acquired during the first 7 days of stay in the intensive care unit. The primary outcomes in studies I and II will be endothelial biomarker levels after HBOT, and in study III suPAR levels as a marker of disease prognosis and severity. ETHICS AND DISSEMINATION: The study has been approved by the Regional Scientific Ethical Committee of Copenhagen (H-16021845) and the Danish Data Protection Agency (RH-2016-199). Results will be presented at national and international conferences and published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier NCT03147352. (Pre-results).

Hyperbaric oxygen therapy may overcome nitric oxide blockage during cyanide intoxication.

PURPOSE: To determine the effects of a blockade of nitric oxide (NO) synthesis on hyperbaric oxygen (HBO2) therapy during cyanide (CN) intoxication. METHODS: 39 anesthetized female Sprague-Dawley rats were exposed to CN intoxication (5.4 mg/kg intra-arterially) with or without previous nitric oxide synthase (NOS) inhibition by L-NG-nitroarginine methyl ester (L-NAME) injection (40 mg/kg intraperitoneally). Subsequently, either HBO2 therapy (284 kPa/90 minutes), normobaric oxygen therapy (100% oxygen/90 minutes) or nothing was administered. Intracerebral microdialysis was used to measure the interstitial brain concentration of lactate, glucose, glycerol and lactate/pyruvate ratios. RESULTS: L-NAME potentiated CN intoxication by higher maximum and prolonged lactate (in mM: 0. 5 ± 0.3 vs. 0.7 ± 0.4, P ⟨ 0.005) concentrations compared with solely CN-intoxicated rats. The same trend was found for mean glucose, glycerol and lactate/pyruvate ratio levels. During HBO2 treatment a sustained reduction occurred in mean lactate levels (in mM: 0.5 ± 0.5 vs. 0.7 ± 0.4, P ⟨ 0.01) regardless of NOS blockade by L-NAME. The same trend was found for mean glucose and glycerol levels. CONCLUSION: The results suggest that blocking NOS using L-NAME can worsen acute CN intoxication. HBO2 treatment can partially overcome this block and continue to ameliorate CN intoxication.