Journal of Applied Physiology, Vol 68, Issue 4 1415-1420, Copyright © 1990 by American Physiological Society
Intravenous injection of propylene glycol causes pulmonary hypertension in sheep
D. A. Quinn, D. Robinson and C. A. Hales
Department of Medicine (Pulmonary/Critical Care and Arthritis Units), Massachusetts General Hospital, Boston.
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)
