TREATING HYPOXIC NEONATAL PIGLETS WITH NG-MONOMETHYL-L-ARGININE AFTER RESUSCITATION WORSENED HEMODYNAMIC RECOVERY DESPITE REDUCING OXIDATIVE STATE

Background Excessive nitric oxide (NO) generated during hypoxic-reoxygenation may cause injuries to the heart and brain. Beneficial effects of reducing NO generation are unclear, especially in asphyxiated newborns who commonly have pulmonary hypertension following resuscitation. Objectives Using a swine model of acute neonatal asphyxia, we evaluated effects of NG-monomethyl-L-arginine (NMMA, a non-selective NO synthase inhibitor) on systemic, pulmonary and carotid hemodynamic changes after reoxygenation. Methods Anesthetized piglets (1–3 d) were instrumented and block-randomized into a sham-operated group (n = 5) and 3 hypoxia-reoxygenation groups (2 h normocapnic alveolar hypoxia followed by 4 h reoxygenation, n = 7/group). At 5 min after reoxygenation, piglets were given either saline or NMMA (0.1[L] or 1[H] mg/kg/h) in a blinded, randomized fashion. Systemic and pulmonary arterial pressures (SAP, PAP, respectively), pulmonary and carotid arterial blood flows were recorded and myocardial and cerebral glutathione and nitrotyrosine levels were compared. Results Asphyxiated piglets were hypotensive, acidotic and had cardiogenic shock. Post-resuscitation NMMA treatment decreased (1) cardiac output and stroke volume (by 28 and 34% and by 26 and 57% of respective values of saline controls for L and H, respectively); (2) carotid oxygen delivery (by 17 and 52% for L and H, respectively) with corresponding changes in carotid flow and vascular resistance during reoxygenation; and (3) myocardial and cerebral oxidized glutathione and nitrotyrosine levels. With no significant improvement in SAP, NMMA treatment caused pulmonary hypertension with increased PAP and PAP/SAP ratio. Conclusions In newborn piglets with hypoxia-reoxygenation, post-resuscitation inhibition of NO production worsened systemic, pulmonary and carotid hemodynamic recovery, despite of reducing oxidative indices.