Relation of arachidonate metabolites to abnormal control of the pulmonary circulation in a child.
To evaluate the role of arachidonate metabolites in regulating pulmonary vascular tone, we performed multiple studies on a 17-month-old girl with idiopathic pulmonary hypertension, systemic arterial hypoxemia (due to ventilation-perfusion mismatching), and an elevated thromboxane A2 (TXA2) to prostacyclin (PGI2) ratio due to increased TXA2 (measured as their stable metabolites, TXB2 and 6-keto-PGF1 alpha, respectively). Intravenous infusions of PGI2 reduced mean pulmonary arterial pressure (from 80 to 47 mmHg), increased cardiac output (from 3.43 to 3.97 L/min), increased systemic arterial oxygen saturation (from 60 to 72 percent), and decreased the TXB2 to 6-keto-PGF1 alpha ratio (from 5.9 to 0.2); mean systemic arterial pressure was unchanged. Pharmacologically decreasing the TXB2 to 6-keto-PGF1 alpha ratio with administration of nifedipine or diltiazem also reduced pulmonary hypertension and increased systemic arterial oxygen saturation in this patient. Nifedipine and diltiazem decreased the ratio by decreasing TXB2. Prostacyclin decreased the ratio by increasing 6-keto-PGF1 alpha. These studies support the hypothesis that the balance between TXA2 and PGI2 is an important influence on pulmonary vascular tone.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000375:Aging; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000627:therapeutic use; D011464:Epoprostenol / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007223:Infant; D009543:Nifedipine / Q000627:therapeutic use; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood; D014652:Vascular Diseases / Q000188:drug therapy / Q000503:physiopathology*; D014664:Vasodilation
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D004110:Diltiazem; D009543:Nifedipine