Inclusion of a Nitric Oxide Congener in the Insufflation Gas Repletes S‐Nitrosohemoglobin and Stabilizes Physiologic Status During Prolonged Carbon Dioxide Pneumoperitoneum

Abstract

IntroductionRecent advances in operative procedures and surgical instrumentation have enabled the application of laparoscopic techniques to more complex surgeries. However, complex procedures require extended insuffl ation times (typically greater than 3 hours) 1-6 and consequently patients undergo prolonged periods of elevated intraabdominal pressure. And while the benefi ts of using minimally invasive techniques for longer procedures are presumed to be similar to those obtained for "simple" laparoscopic surgeries, it is now recognized that carbon dioxide (CO 2 ) pneumoperitoneum and the resultant rise in intra-abdominal pressure can produce reductions in organ blood fl ow, acidosis, and alterations in cardiovascular and respiratory status, 5-10 all of which can impact postoperative organ function and patient recovery; the severity of these eff ects correlates to the duration of insuffl ation. 11To some extent, the acidosis and systemic effects of pneumoperitoneum can be controlled by altering ventilation rates and/or administration of vasoactive agents but such interventions have minimal ability to preserve end-organ blood fl ow and oxygen delivery. Th is is because local tissue blood fl ow, rather than blood oxygen content, is the primary determinant of oxygen delivery. Local tissue perfusion is regulated by a physiological response termed hypoxic vasodilation in which tissue oxygen requirements are directly coupled to blood fl ow, the domain of nitric oxide (NO) bioactivity.12 Second to second changes in microcirculatory fl ow are controlled by complex interactions between oxygen, NO, and hemoglobin (Hb) within the red blood cell with Hb serving as an oxygen sensor and as a hypoxia-responsive transducer of NO signals. 13,14 Vasodilation by S-nitrosoHb (SNO-Hb; i.e., release of NO bioactivity) is linked to Hb desaturation and provides a regulated mechanism for matching blood fl ow and oxygen delivery with local metabolic demand. 15Decreased levels and/or impaired processing of SNO-Hb have been observed in disparate diseases characterized by tissue hypoxemia; [16][17][18][19][20][21][22] where examined, red blood cells from these patients exhibited impaired vasodilatory capacity. Such data suggest that red blood cell derived NO bioactivity plays an important role in the respiratory cycle and that impairment of this activity might contribute to the pathophysiology of ischemic conditions. Based on these fi ndings, we reasoned that insuffl ationinduced reductions in splanchnic blood fl ow may be due, at least in part, to alterations (reductions) in SNO-Hb homeostasis. By extension, an intervention directed toward increasing NO bioactivity could potentially ameliorate pneumoperitoneuminduced reductions in organ blood fl ow. Th eoretical support for this hypothesis comes from the observations that reductions in blood pH, as occur during CO 2 pneumoperitoneum, accelerate SNO-Hb decay 23,24 and increased mechanical ventilation (as may be initiated to control hybercarbia) increases the concentration of exhaled NO 25 b...

S-nitrosylation: integrator of cardiovascular performance and oxygen delivery

“…One contributory explanation for this apparent paradox is that banked blood is depleted of SNO and fails to deliver bioactive NO, and can therefore exacerbate tissue hypoxia (123)(124)(125). Accordingly, strategies aimed at restoring SNO levels in rbc (96,126) may represent an attractive strategy to improve NO delivery, myocardial performance, and tissue oxygenation.…”

Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle

“…Thus, baseline tone at a given pO 2 may be regulated further by RBC-based HVD (acute changes, over seconds) (53,62,97,99). Hypercarbia and acidosis are additional effectors of the T-conformation in Hb and may thereby promote vasodilation by RBCs (250). Furthermore, oxidation of hemes can elicit a T-like conformation in SNO-Hb to promote NO release (149,228).…”

Effect of Processing and Storage on Red Blood Cell Function In Vivo

“…Thus, baseline tone appears to be regulated further by RBC-based HVD (acute changes, over seconds) 51, 60, 66, 73 . Hypercarbia and acidosis are additional effectors of the T-conformation in Hb, and thereby also promote vasodilation by RBCs 116 . Furthermore, oxidation of hemes can elicit a T-like conformation in SNO-Hb to promote NO release 54, 113 .…”