Cromolyn sodium does not prevent hypoxia-induced pulmonary hypertension in newborn and young lambs.
Hypoxia-induced pulmonary hypertension may be mediated by leukotrienes. Pulmonary mast cells produce leukotrienes, histamine and prostaglandin D2, and degranulate in response to hypoxia. Cromolyn sodium, a mast cell membrane stabilizing agent, may prevent hypoxia-induced mast cell degranulation. To investigate the role of mast cell products in hypoxia-induced pulmonary hypertension, we studied the haemodynamic responses to alveolar hypoxia before and during an intravenous infusion of 3-5 mg/min per kg of cromolyn sodium in 6 chronically instrumented, spontaneously breathing lambs. Since there are age-dependent differences in the response of the pulmonary circulation to some mast cell products, we studied the effects of cromolyn sodium on hypoxia-induced pulmonary hypertension in newborn (4-7 days) and young lambs (15-18 days). During alveolar hypoxia, mean pulmonary arterial pressure increased by 68% (P less than 0.05) and 59% (P less than 0.05) in the newborn and young lambs, respectively. With alveolar hypoxia during cromolyn sodium infusion, mean pulmonary arterial pressure increased by 71% (P less than 0.05) and 42% (P less than 0.05) in the newborn and young lambs, respectively. Cromolyn sodium did blunt the hypoxia-induced release of histamine into the circulation. Because hypoxia-induced pulmonary hypertension was not inhibited by cromolyn sodium in either age group, mast cell products are not important mediators of hypoxia-induced pulmonary hypertension.
Frantz
E G
EG
Cardiovascular Research Institute, University of California, San Francisco 94143.
Schreiber
M D
MD
Soifer
S J
SJ
D000818:Animals; D000831:Animals, Newborn; D004205:Cromolyn Sodium / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep / Q000502:physiology*
D004205:Cromolyn Sodium