Inhibiting nitric oxide overproduction during hypotensive sepsis increases local oxygen consumption in rat skeletal muscle.

OBJECTIVE

Although nitric oxide (NO) is a known regulator of cardiovascular function, the effect of NO overproduction during sepsis on capillary oxygen transport and local tissue oxygen consumption is not well understood. The objectives of this study were to determine whether sepsis-induced NO overproduction increased capillary stopped-flow and modulated tissue oxygen consumption in skeletal muscle.

DESIGN

Prospective, controlled laboratory study.

SETTING

Animal laboratory in a university-affiliated research institute.

SUBJECTS: Male Sprague-Dawley rats, 165-180 g body weight.

INTERVENTIONS: Rats were made septic by cecal ligation and perforation (CLP) and were then ventilated and volume resuscitated (saline). The hind limb extensor digitorum longus (EDL) skeletal muscle was blunt dissected for in vivo microvascular imaging. The inducible NO synthase (iNOS) inhibitor L-N6-(1-iminoethyl)lysine dihydrochloride (L-NIL) was infused (3 mg/kg body weight per hour) starting 1 hr post-CLP to maintain arterial blood and EDL tissue NO(x)(-) (NO2(-) + NO3(-)) at baseline.

MEASUREMENTS AND MAIN

RESULTS

Red blood cell hemodynamics, hemoglobin oxygen saturation, capillary geometry, and functional capillary density information were used to calculate capillary oxygen flux (the rate of oxygen diffusion from capillary to tissue) and indices of local oxygen delivery and tissue oxygen consumption. Over the first 5 hrs of septic injury, mean arterial pressure decreased while capillary stopped-flow and capillary oxygen flux both increased (p < .05). Inhibiting iNOS/NO overproduction partially restored mean arterial pressure and increased arterial pH. Within the microcirculation, inhibiting NO increased capillary red cell velocity and increased local tissue oxygen consumption (p < .05). Inhibiting NO failed, however, to prevent capillary stopped-flow.

CONCLUSIONS

During the onset of sepsis, concurrent with the onset of microvascular dysfunction, there is an iNOS/NO-mediated reduction in local skeletal muscle tissue oxygen consumption.