It has been shown that nitrite can be reduced to nitric oxide (NO) in intestine and a number of other tissues and released into the blood to form nitrosylhemoglobin (NO-Hb), existing in an equilibrium with S-nitrosohemoglobin. The latter has been suggested to be an NO transporter to distant organs. The aim of this study was to define the pathway of nitrite reduction to form NO in intestinal wall and to estimate whether this pathway has an effect on peripheral circulation. We have shown that in rat intestine at pH 7.0 70% of nitrite is converted to NO in mitochondria. At pH 6.0, nonenzymatic nitrite reduction becomes as efficient as the mitochondrial pathway. To prove whether the NO formed from nitrite in intestine can induce vasodilatation, sodium nitrite was instilled into intestinal lumen and the concentration of NO formed and diffused into the blood was followed by measuring of NO-Hb complex formation. We found that the concentration of NO-Hb gradually increases with the increase of nitrite concentration in intestinal lumen. However, it was not always accompanied by a decrease in systemic blood pressure. Blood pressure dropped down only after NO-Hb reached a threshold concentration of approximately 10 microM. These data show that NO-Hb cannot provide enough NO for vasodilatation if the concentration of NO bound to Hb is< 10 microM. The exact mechanism underlying vasodilatation observed when the concentration of NO-bound Hb was > 10 microM is, however, not clear yet and requires further studies.

Nitric monoxide (NO) exerts a great variety of physiological functions. L-Arginine supplies amino groups which are transformed to NO in various NO-synthase-active isoenzyme complexes. NO-synthesis is stimulated under various conditions increasing the tissue of stable NO-metabolites. The major oxidation product found is nitrite. Elevated nitrite levels were reported to exist in a variety of diseases including HIV, reperfusion injury and hypovolemic shock. Denitrifying bacteria such as Paracoccus denitrificans have a membrane bound set of cytochromes (cyt cd1, cyt bc) which were shown to be involved in nitrite reduction activities. Mammalian mitochondria have similar cytochromes which form part of the respiratory chain. Like in bacteria quinols are used as reductants of these types of cytochromes. The observation of one-e- divergence from this redox-couple to external dioxygen made us to study whether this site of the respiratory chain may also recycle nitrite back to its bioactive form NO. Thus, the aim of the present study was therefore to confirm the existence of a reductive pathway which reestablishes the existence of the bioregulator NO from its main metabolite NO2-. Our results show that respiring mitochondria readily reduce added nitrite to NO which was made visible by nitrosylation of deoxyhemoglobin. The adduct gives characteristic triplet-ESR-signals. Using inhibitors of the respiratory chain for chemical sequestration of respiratory segments we were able to identify the site where nitrite is reduced. The results confirm the ubiquinone/cyt be1 couple as the reductant site where nitrite is recycled. The high affinity of NO to the heme-iron of cytochrome oxidase will result in an impairment of mitochondrial energy-production. "Nitrite tolerance" of angina pectoris patients using NO-donors may be explained in that way.

Based on an extensive literature search, which produced 21 observations, the etiology, symptoms, imaging features, clinical significance, treatment strategy, and outcome of HPVG because of colonic diverticulitis are evaluated: While observations with an underlying intramesocolic abscess carry a favorable prognosis, the prognosis of observations because of septic thrombophlebitis with gas forming germs is poor.

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Patients with hemorrhagic shock and/or trauma are at risk of developing colonic ischemia associated with bacterial translocation that may lead to multiple organ failure and death. Intestinal ischemia is difficult to diagnose noninvasively. The present retrospective study was designed to determine whether circulating plasma D-lactate is associated with mortality in a clinically relevant two-hit model in baboons. Hemorrhagic shock was induced in anesthetized baboons (n = 24) by controlled bleeding (mean arterial pressure, 40 mmHg), base excess (maximum -5 mmol/L), and time (maximum 3 h). To mimic clinical setting more closely, all animals underwent a surgical trauma after resuscitation including midshaft osteotomy stabilized with reamed femoral interlocking nailing and were followed for 7 days. Hemorrhagic shock/surgical trauma resulted in 66% mortality by day 7. In nonsurvivor (n = 16) hemorrhagic shock/surgical trauma baboons, circulating D-lactate levels were significantly increased (2-fold) at 24 h compared with survivors (n = 8), whereas the early increase during hemorrhage and resuscitation declined during the early postresuscitation phase with no difference between survivors and nonsurvivors. Moreover, D-lactate levels remained elevated in the nonsurvival group until death, whereas it decreased to baseline in survivors. Prediction of death (receiver operating characteristic test) by D-lactate was accurate with an area under the curve (days 1-3 after trauma) of 0.85 (95% confidence interval, 0.72-0.93). The optimal D-lactate cutoff value of 25.34 μg/mL produced sensitivity of 73% to 99% and specificity of 50% to 83%. Our data suggest that elevation of plasma D-lactate after 24 h predicts an increased risk of mortality after hemorrhage and trauma.