Inclusion of a nitric oxide congener in the insufflation gas repletes S-nitrosohemoglobin and stabilizes physiologic status during prolonged carbon dioxide pneumoperitoneum - PubMed (original) (raw)

doi: 10.1111/j.1752-8062.2009.00154.x.

Kenichiro Uemura, Kathryn M Auten, Matthew F Baldwin, Samuel W Belknap, Francisco La Banca, Maximilian C Jones, Deborah J McClaine, Rebecca J McClaine, W Steve Eubanks, Jonathan S Stamler, James D Reynolds

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Inclusion of a nitric oxide congener in the insufflation gas repletes S-nitrosohemoglobin and stabilizes physiologic status during prolonged carbon dioxide pneumoperitoneum

Kazufumi Shimazutsu et al. Clin Transl Sci. 2009 Dec.

Abstract

A method to maintain organ blood flow during laparoscopic surgery has not been developed. Here we determined if ethyl nitrite, an S-nitrosylating agent that would maintain nitric oxide bioactivity (the major regulator of tissue perfusion), might be an effective intervention to preserve physiologic status during prolonged pneumoperitoneum. The study was conducted on appropriately anesthetized adult swine; the period of pneumoperitoneum was 240 minutes. Cohorts consisted of an anesthesia control group and groups insufflated with CO2 alone or CO2 containing fixed amounts of ethyl nitrite (1-300 ppm). Insufflation with CO2 alone produced declines in splanchnic organ blood flows and it reduced circulating levels of S-nitrosohemoglobin (i.e., nitric oxide bioactivity); these reductions were obviated by ethyl nitrite. In a specific example, preservation of kidney blood flow with ethyl nitrite kept serum creatinine and blood urea nitrogen concentrations constant whereas in the CO2 alone group both increased as kidney blood flow declined. The data indicate ethyl nitrite can effectively attenuate insufflation-induced decreases in organ blood flow and nitric oxide bioactivity leading to reductions in markers of acute tissue injury. This simple intervention provides a method for controlling a major source of laparoscopic-related morbidity and mortality: tissue ischemia and altered postoperative organ function.

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Figures

Figure 1

Figure 1

Time course of red blood cell _S‐_nitrosohemoglobin (SNO‐Hb) concentrations during and after insufflation with CO2 (_n_= 6; hatched line) or CO2 plus 50 ppm ethyl nitrite (ENO; _n_= 7; solid line). Intra‐abdominal pressure was kept at 15 mmHg during the 240‐minute period of insufflation (box). Data are expressed as mean ± standard deviation. SNO‐Hb concentrations in the CO2 alone group were significantly different from those in the 50 ppm ENO cohort at the 180 and 240 minute marks (p < 0.05).

Figure 2

Figure 2

Arterial and venous blood gas values for pH, pCO2, and oxygen saturation recorded during the course of the study for the anesthesia control group (solid square, _n_= 11), the CO2 alone group (open triangle, _n_= 11), and the animals insufflated with either 1 (open square, _n_= 10) or 10 (open circle, _n_= 10) ppm ethyl nitrite; parameters are presented in standard units. The period of insufflation is demarcated by the black rectangle. Animals were well oxygenated during the course of the study but similar degrees of acidosis and hybercarbia occurred in all groups that were insufflated despite maintaining end‐tidal CO2 below 35 mmHg. Time‐points marked with an asterisk (*) indicate where the values for the insufflation groups are significantly different from their respective baseline values (p < 0.05).

Figure 3

Figure 3

Heart rate, mean arterial pressure, and cardiac output changes during the course of the study for the anesthesia alone group (_n_= 11), the CO2 alone group (_n_= 11), and the animals insufflated with either 1 or 10 ppm ethyl nitrite (both, _n_= 10). Insufflation with CO2 alone produced an initial rise in heart rate that resolved after about 90 minuets; the heart rate changes observed with the other experimental groups were not significant. Mean arterial pressure was elevated for the duration of the study in the 1 and 10 ppm ethyl nitrite treatment groups. In addition, cardiac output increased during insufflation with 10 ppm ethyl nitrite. (See text for a description of the statistical comparisons.)

Figure 4

Figure 4

Time course and temporal relationship between kidney blood flow and serum creatinine. Neither parameter changed in the anesthesia control group (_n_= 11); they also remained constant in the animals insufflated with 1 or 10 ppm ethyl nitrite (both, _n_= 10). In contrast, insufflation with CO2 alone (_n_= 11) significantly reduced kidney blood flow (time points marked with a †) and significantly increased serum creatinine (marked with an *), with the latter remaining elevated 2 hours after desufflation (p < 0.05).

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