Selective pulmonary vasodilation with ATP-MgCl2 during pulmonary hypertension in lambs.
We investigated the effects of infusions of ATP-MgCl2 on the circulation in 11 spontaneously breathing newborn lambs during pulmonary hypertension induced either by the infusion of U-46619, a thromboxane A2 mimetic, or by hypoxia. During pulmonary hypertension induced by U-46619, ATP-MgCl2 (0.01-1.0 mg.kg-1.min-1) caused a significant dose-dependent decrease in pulmonary arterial pressure (12.4-40.7%, P less than 0.05), while systemic arterial pressure decreased only at the highest doses (P less than 0.05). Left atrial infusions of ATP-MgCl2 caused systemic hypotension without decreasing pulmonary arterial pressure. During hypoxia-induced pulmonary hypertension, ATP-MgCl2 caused a similar significant dose-dependent decrease in pulmonary arterial pressure (12.0-41.1%, P less than 0.05), while systemic arterial pressure decreased only at high doses (P less than 0.05). Regression analysis showed selectivity of the vasodilating effects of ATP-MgCl2 for the pulmonary circulation during pulmonary hypertension induced either by U-46619 or hypoxia. ATP-MgCl2 is a potent vasodilator with a rapid metabolism that allows for selective vasodilation of the vascular bed first encountered (pulmonary or systemic). We conclude that infusions of ATP-MgCl2 may be clinically useful in the treatment of children with pulmonary hypertension.
Fineman
J R
JR
Department of Pediatrics, University of California, San Francisco 94143.
Crowley
M R
MR
Soifer
S J
SJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications; D011450:Prostaglandin Endoperoxides, Synthetic; D011652:Pulmonary Circulation / Q000187:drug effects*; D012146:Rest; D012756:Sheep; D014664:Vasodilation
D011450:Prostaglandin Endoperoxides, Synthetic; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate