Cyclo-oxygenase products mediate hypoxic pulmonary hypertension.
High-risk infants with a fetal pattern of circulation demonstrate hyperactivity of the pulmonary vascular bed in response to stimuli including mucous plugging, atelectasis, and endotrachial tube suctioning. The resultant increase in pulmonary vascular resistance (PVR) leads to pulmonary hypertension, severe right-to-left shunting, and hypoxemia. Stimuli that trigger pulmonary hypertension cause hypoxia, suggesting the importance of hypoxic pulmonary vasoconstriction (HPV). Although many humoral mediators of HPV have been hypothesized, none have been proven. This study investigates the possible role of the cyclo-oxygenase derivatives thromboxane A2 and prostacyclin as determinants of hypoxic pulmonary hypertension. Open-chested lambs were ventilated with 13% O2 prior to and following treatment with OKY 046, a selective thromboxane inhibitor. In untreated lambs, the partial pressure of arterial oxygen fell from 80 +/- 27 (mean +/- SD) to 35 +/- 13 mm HG (P less than .01). The mean arterial pressure (MAP) remained at 50 +/- 7 mm HG, and the cardiac output (CO) was unchanged at 0.8 +/- 0.2 L/min. The mean pulmonary arterial pressure (MPAP) rose from 11 +/- 4 to 20 +/- 4 mm HG (P less than .01) whereas the PVR increased 70% (P less than .01). TxB2 rose from 147 +/- 85 to 271 +/- 154 pg/mL (P less than .05), and 6-keto-PGF1 alpha rose from 105 +/- 96 to 142 +/- 110 pg/mL. These substances are the hydrolysis products of TxA2 and prostacyclin respectively. In animals treated with OKY 046 prior to ventilation with 13% O2, values for MAP, CO, and PVR were similar to those of the nontreatment period.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D011464:Epoprostenol / Q000097:blood*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D012756:Sheep; D013928:Thromboxane A2 / Q000097:blood*
D008689:Methacrylates; D013928:Thromboxane A2; D011464:Epoprostenol; C034364:ozagrel; D010100:Oxygen