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Nitrite consumption and production in the cardiopulmonary circulation during hemorrhagic shock and resuscitation


Nitrite (NO2-) is reduced to nitric oxide (NO) by deoxyhemoglobin, and resynthesized in blood by oxidation of NO in the presence of ceruloplasmin. The central circulation seems a probable site for nitrite consumption and repletion during periods of oxidative stress and recovery such as that seen in hemorrhagic shock and resuscitation (HSR). We asked whether NO2- is consumed in the central circulation during hemorrhage, and reconstituted during resuscitation.


Male Sprague–Dawley rats (n = 13) were anesthetized, ventilated via tracheostomy, and then underwent HSR by withdrawing venous blood to a target systolic pressure of 40% of baseline, waiting 30 minutes and then resuscitating with saline to prebleed mean arterial pressure. Whole blood NO2-(arteriovenous NO2-) and exhaled NO (NOexh) (measured by chemiluminescence), blood gases and hemodynamics were sampled at baseline, at the end of hemorrhage, after 20 minutes autoresuscitation, and after saline resuscitation. Mass flow of NO2- (mass NO2-) across the central circulation was calculated as the product of arteriovenous difference and blood flow.


Figure 1 shows changes (± SEM) in hemodynamics, arterial and venous whole blood nitrite, and NOexh during HSR. Mass flow of NO2- decreased acutely with hemorrhage and NOexh increased, suggesting consumption of NO2- to NO across the central circulation. Conversely, during autoresuscitation, mass flow increased and NOexh decreased – suggesting production of NO2-.

figure 1

Figure 1


Our findings are consistent with the hypothesis that NO2- consumption to NO is involved in the hemodynamic response to HSR. We also provide evidence that the lung is a major site of repletion of the NO2- pool, presumably by oxidation of NO to NO2- during both autoresuscitation and saline resuscitation.

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Phillips, C., Wong, C., Oyama, T. et al. Nitrite consumption and production in the cardiopulmonary circulation during hemorrhagic shock and resuscitation. Crit Care 12 (Suppl 2), P383 (2008).

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