Abstract
ABSTRACT: Although tolazoline is the most commonly used drug in the treatment of neonatal pulmonary hypertension, its mode of action and efficacy remain incompletely understood. In order to study the effects of tolazoline on a high resistance pulmonary circulation and to better understand mechanisms that control pulmonary vascular tone and reactivity in the fetus, we infused tolazoline either continuously or as bolus into the left pulmonary artery of 15 chronically instrumented, normoxic fetal lambs during late gestation. The vasodilatory effects of bolus injections of tolazoline (2.5 mg) were inhibited by the prior administration of the histaminergic receptor blockers, cimetidine (56%), diphenhydramine (56%), or both (100%). During the continuous infusion of tolazoline (4.5 mg/h for 9 min), pulmonary blood flow to the left lung increased from 61 ± 6 ml/min (mean ± SE; control) to 100 ± 10 (peak) at 30 min (P<0.001). However, following this initial vasodilatation, pulmonary blood flow steadily decreased toward control values by 90 min, despite the continued infusion of tolazoline (P<0.001). Although the calcium channel blocker, verapamil, and the a-adrenergic blocker, phentolamine, had little effect on fetal pulmonary blood flow when infused alone, both drugs increased the vasodilatory response to tolazoline (P<0.001). We conclude that tolazoline effects pulmonary vasodilatation by a histaminergic mechanism and that subsequent refractoriness to the drug is a calcium-dependent process which may be partially mediated by an a-adrenergic mechanism.
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Abman, S., Wilkening, R., Ward, R. et al. Adaptation of Fetal Pulmonary Blood Flow to Local Infusion of Tolazoline. Pediatr Res 20, 1131–1135 (1986). https://doi.org/10.1203/00006450-198611000-00013
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DOI: https://doi.org/10.1203/00006450-198611000-00013