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

TY - JOUR

T1 - Neuronal nitric oxide inhibition attenuates the protective effect of HBO2 during cyanide poisoning

AU - Hedetoft, Morten

AU - Polzik, Peter

AU - Olsen, Niels Vidiendal

AU - Hyldegaard, Ole

N1 - Copyright© Undersea and Hyperbaric Medical Society.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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] + 7-nitroindazole [25 mg/kg 7-nitroindazole via intraperitoneal injection]; 3) cyanide+7-nitroindazole + HBO2 [284 kPa for 90 minutes]; 4) cyanide + 7-nitroindazole + 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.

AB - 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] + 7-nitroindazole [25 mg/kg 7-nitroindazole via intraperitoneal injection]; 3) cyanide+7-nitroindazole + HBO2 [284 kPa for 90 minutes]; 4) cyanide + 7-nitroindazole + 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.

UR - https://www.uhms.org/doi-articles/751-neuronal-nitric-oxide-inhibition-attenuates-the-protective-effect-of-hbo2-during-cyanide-poisoning.html

U2 - 10.22462/05.06.2018.9

DO - 10.22462/05.06.2018.9

M3 - Journal article

C2 - 30028920

SN - 1066-2936

VL - 45

SP - 335

EP - 350

JO - Undersea & Hyperbaric Medicine

JF - Undersea & Hyperbaric Medicine

IS - 3

ER -