Abstract
IntroductionTissue 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.MethodsTwenty pigs (mean wt. 30.6 kg, range 27.2 to 36.4 kg) 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 20 ml/min to a mean arterial pressure of 30 mmHg and kept between 30 and 40 mmHg for 90 minutes and then resuscitated. One pig was instrumented but not bled (sham). Hemorrhaged animals were randomized to inhale nothing (control, n = 7), 11 mg nitrite (nitrite, n = 7) or 250 ppm CO (CO, n = 5) over 30 minutes 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.ResultsNeither 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.ConclusionsWe conclude that small doses of nebulized sodium nitrite or inhaled CO may be associated with intestinal protection during resuscitation from severe hemorrhagic shock.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0903-z) contains supplementary material, which is available to authorized users.
Highlights
Tissue reperfusion following hemorrhagic shock may paradoxically cause tissue injury and organ dysfunction by mitochondrial free radical expression
Mesquida et al showed that tissue oxygen saturation measured in the thenar eminence by near-infrared spectroscopy had a weak correlation to mixed venous oxygen saturation (SvO2) [6]
All animals appeared healthy upon arrival and tolerated the surgical procedure, including insertion of microdialysis catheters, well and bleeding and resuscitation phases of the protocol were carried out without untoward complications
Summary
Tissue reperfusion following hemorrhagic shock may paradoxically cause tissue injury and organ dysfunction by mitochondrial free radical expression. The fundamental assumption in resuscitation physiology is that shock represents inadequate perfusion of the tissues to meet their metabolic demand and that rapid restoration of macrocirculatory perfusion pressure and blood flow will reverse this hypoperfusion, minimizing tissue injury and promoting recovery. It is unknown how resuscitation based on macrohemodynamic parameters impacts tissue wellness in the setting of hemorrhagic shock. Hernandez et al recently showed that dobutamine-induced increases in macrocirculatory parameters did not translate into an improved microcirculatory flow or an improved organ system function in septic patients [7] It is unclear if manipulating the macrocirculation will proportionally benefit the microcirculation after the development of tissue ischemia
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