Nitric oxide (NO.) has been proposed to modulate hypoxic vasoconstriction in the lung. The activity of nitric oxide synthase (NOS) can be inhibited by hypoxia because molecular oxygen is a necessary substrate for the enzyme. On the basis of this mechanism, we hypothesized that NOS activity has a key role in regulation of pulmonary vascular tone during hypoxia. We measured oxidation products of NO. released into the vasculature of isolated buffer-perfused rabbit lung ventilated with normoxic (21% O2), moderately hypoxic (5% O2), or anoxic (0% O2) gas using two methods. Mean PO2 in perfusate exiting the lung was 25 Torr during anoxic ventilation and 47 Torr during moderately hypoxic ventilation. We found that the amount of the NO. oxidation product nitrite released into the perfusate was suppressed significantly during ventilation with anoxic but not moderately hypoxic gas. During normoxic ventilation, nitrite release was inhibited by pretreatment with NG-monomethyl-L-arginine, a competitive inhibitor of NOS. To confirm that changes in nitrite concentration reflected changes in NO. release into the perfusate, major oxidation products of NO. (NOx) were assayed using a method for reduction of these products to NO. by vanadium(III) Cl. Release of NOx into the perfusate was suppressed by severe hypoxia (anoxic ventilation), and this effect was reversed by normoxia. Pulmonary vasoconstriction was observed during severe but not moderate hypoxia and was related inversely to the rate of nitrite release. These observations provide evidence that decreased NO. production contributes to the pulmonary vasoconstrictor response during severe hypoxia.

Objectives. To correlate the initial and maximal lactate levels with the occurrence of intracranial hemorrhage (ICH) and survival in patients treated with extracorporeal life support (ECLS). Design. Retrospective chart review. Setting. Pediatric intensive care unit. Patients. Eighty-two neonatal patients placed on ECLS for respiratory failure due to sepsis, meconium aspiration, or persistent pulmonary hypertension of the newborn. Measurements. The initial lactate level measured within 6 hours of initiating ECLS and the maximal lactate level measured throughout the ECLS course were collected. Lactate levels were described as mean lactate ± SE (mM). Head ultrasound reports and survival were reviewed. Platelet counts and activated clotting times (ACTs) were examined. Results. The mean initial and maximal lactate levels were higher in ECLS patients who developed ICH (initial: 10 ± 1.7 mM vs 6.4 ± 0.8 mM, p = .05 and maximal: 12.4 ± 2.5 mM vs 7.9 ± 0.8 mM, p = .04). Initial and maximal lactate levels were also elevated in nonsurvivors (initial: 11.7 ± 3 mM vs 6.4 ± 0.7 mM, p = .01 and maximal: 14.8 ± 3.3 mM vs 7.8 ± 0.8 mM, P < .01). Platelet counts and ACT did not differ in patients with and without ICH. Conclusions. Lactate is a useful marker for the development of ICH in ECLS patients. In addition, elevated lactates during ECLS identify a subgroup of patients with poor outcome. Prospective studies are needed to determine whether the incorporation of this information into pre-ECLS and ECLS management will decrease the occurrence of ICH and improve survival.

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