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Effects of inhalation of low-dose nitrite or carbon monoxide on post-reperfusion mitochondrial function and tissue injury in hemorrhagic shock swine

Haugaa, H and Gómez, H and Maberry, DR and Holder, A and Ogundele, O and Quintero, AMB and Escobar, D and Tønnessen, TI and Airgood, H and Dezfulian, C and Kenny, E and Shiva, S and Zuckerbraun, B and Pinsky, MR (2015) Effects of inhalation of low-dose nitrite or carbon monoxide on post-reperfusion mitochondrial function and tissue injury in hemorrhagic shock swine. Critical Care, 19 (1). ISSN 1364-8535

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Introduction: Tissue reperfusion following hemorrhagic shock may paradoxically cause tissue injury and organ dysfunction by mitochondrial free radical expression. Both nitrite and carbon monoxide (CO) may protect from this reperfusion injury by limiting mitochondrial free radial production. We explored the effects of very small doses of inhaled nitrite and CO on tissue injury in a porcine model of hemorrhagic shock. Methods: Twenty pigs (mean wt. 30.6kg, range 27.2 to 36.4kg) had microdialysis catheters inserted in muscle, peritoneum, and liver to measure lactate, pyruvate, glucose, glycerol, and nitrite. Nineteen of the pigs were bled at a rate of 20ml/min to a mean arterial pressure of 30mmHg and kept between 30 and 40mmHg for 90minutes and then resuscitated. One pig was instrumented but not bled (sham). Hemorrhaged animals were randomized to inhale nothing (control, n=7), 11mg nitrite (nitrite, n=7) or 250ppm CO (CO, n=5) over 30minutes before fluid resuscitation. Mitochondrial respiratory control ratio was measured in muscle biopsies. Repeated measures from microdialysis catheters were analyzed in a random effects mixed model. Results: Neither nitrite nor CO had any effects on the measured hemodynamic variables. Following inhalation of nitrite, plasma, but not tissue, nitrite increased. Following reperfusion, plasma nitrite only increased in the control and CO groups. Thereafter, nitrite decreased only in the nitrite group. Inhalation of nitrite was associated with decreases in blood lactate, whereas both nitrite and CO were associated with decreases in glycerol release into peritoneal fluid. Following resuscitation, the muscular mitochondrial respiratory control ratio was reduced in the control group but preserved in the nitrite and CO groups. Conclusions: We conclude that small doses of nebulized sodium nitrite or inhaled CO may be associated with intestinal protection during resuscitation from severe hemorrhagic shock.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Haugaa, H
Gómez, H
Maberry, DR
Holder, Aholder@pitt.eduHOLDER
Ogundele, O
Quintero, AMB
Escobar, D
Tønnessen, TI
Airgood, H
Dezfulian, Ccad117@pitt.eduCAD1170000-0002-4486-0446
Kenny, Eemk76@pitt.eduEMK76
Shiva, Ssss43@pitt.eduSSS43
Zuckerbraun, Bzuckerbr@pitt.eduZUCKERBR
Pinsky, MRpinsky@pitt.eduPINSKY0000-0001-6166-700X
Centers: Other Centers, Institutes, Offices, or Units > Vascular Medicine Institute
Date: 14 December 2015
Date Type: Publication
Journal or Publication Title: Critical Care
Volume: 19
Number: 1
DOI or Unique Handle: 10.1186/s13054-015-0903-z
Schools and Programs: School of Medicine > Critical Care Medicine
School of Medicine > Pharmacology and Chemical Biology
School of Medicine > Surgery
Refereed: Yes
ISSN: 1364-8535
Date Deposited: 30 Aug 2016 16:21
Last Modified: 31 Mar 2021 00:55


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