The effect of repeated intermittent hypoxia on pulmonary vasoconstriction in the newborn

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Abstract
The effect of repeated intermittent hypoxia upon the basal pulmonary vascular tone in the newborn period is unknown. We therefore studied the central hemodynamic response to seven repeated intermittent hypoxic challenges in acutely prepared piglets under 2 weeks of age. Catheters were placed in the aorta, pulmonary artery, and atria, and an electromagnetic flow probe was positioned around the main pulmonary artery. Each hypoxic challenge (Fio2 = 0.14) lasted 5 min, and was separated by an equal duration of ventilation with air. Nine control animals were ventilated with air for 90 min, a period of time equivalent to the seven challenges in the experimental group, and subjected to one hypoxic challenge at the end. Hypoxia uniformly induced pulmonary vasoconstriction. Repeated intermittent hypoxic challenges produced a progressive increase in pulmonary artery pressure and vascular resistance, both during air ventilation and hypoxia. For each challenge, the vascular resistance value achieved during hypoxia was directly related to the immediately preceding air ventilation one, and the magnitude of hypoxic pulmonary vasoconstriction, defined as the incremental change in resistance from air to hypoxia, was not different from the first to the last challenge in the experimental group. In the control group the pulmonary vascular tone did not change during the 90 min of air ventilation, and the single hypoxic challenge induced an increase in pulmonary vascular pressure and resistance similar in magnitude to the first challenge in the experimental group. Indomethacin administration to five experimental animals, after the last challenge, reversed the increase in air ventilation pulmonary artery pressure and vascular resistance. Plasma levels of thromboxane B2 and 6-keto-PGF1α were also measured by an enzyme immunoabsorbent assay in half the experimental animals. Surgical stress was associated with a significant rise in both prostaglandin metabolites. Repeated hypoxic challenges led to a further increase in thromboxane B2 and also in the ratio of this metabolite and 6-keto-PGF1α (p < 0.05). The percentage increase in the latter was linearly correlated with the increase in pulmonary arterial pressure and vascular resistance from the first to the last hypoxic challenge. These data indicate that repeated intermittent hypoxia in the newborn pig increases the pulmonary vascular resistance on air ventilation. This phenomenon is possibly related to the release of the potent pulmonary vasoconstrictor thromboxane A2, and may play a role in the pathogenesis of the persistent pulmonary hypertension in human infants who underwent repeated perinatal hypoxic insults.Key words: persistent pulmonary hypertension syndrome, hypoxic pulmonary vasoconstriction, newborn, prostaglandins.