Intravenous injection of propylene glycol causes pulmonary hypertension in sheep.
Propylene glycol (30%) is the carrier base for pentobarbital sodium in preparations often used in research laboratories. It has caused pulmonary hypertension in calves, and we found it caused pulmonary hypertension in sheep as well. To investigate the mechanism of pulmonary hypertension with propylene glycol, we injected an average loading dose of 30% propylene glycol (0.5 ml/kg) into adult sheep, which was followed by a rise in thromboxane levels (P less than 0.05) in systemic arterial plasma and lung lymph and by a dramatic increase in pulmonary arterial pressure (17 +/- 1 to 35 +/- 4 mmHg, P less than 0.05) and a fall in cardiac output (2.7 +/- 0.5 to 1 +/- 0.2 l/min). Indomethacin pretreatment blocked the rise in thromboxane in lung lymph and arterial plasma and substantially, although not entirely, blocked the rise in pulmonary arterial pressure. Pulmonary intravascular macrophages (PIMS), which are present in sheep and calves, can release thromboxane in response to a stimulus. To test whether PIMS might be the source of the thromboxane and pulmonary hypertension, we injected propylene glycol into guinea pigs and dogs, which are reported to have no PIMS, as well as into newborn lambs, which are not believed to develop many PIMS until the 2nd wk of life. In dogs and guinea pigs there was no response to propylene glycol. In lambs there was a rise in pulmonary vascular resistance but significantly less than in adult sheep; indomethacin blocked this response.(ABSTRACT TRUNCATED AT 250 WORDS)
Quinn
D A
DA
Department of Medicine (Pulmonary/Critical Care and Arthritis Units), Massachusetts General Hospital, Boston.
Robinson
D
D
Hales
C A
CA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D008196:Lymph / Q000378:metabolism; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000008:administration & dosage; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure; D012756:Sheep; D013931:Thromboxanes / Q000097:blood / Q000378:metabolism*; D014655:Vascular Resistance
D011409:Propylene Glycols; D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; D019946:Propylene Glycol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007213:Indomethacin