Effects of oleic acid-, alpha-naphthylthiourea-, and phorbol myristate acetate-induced microvascular damage on indexes of pulmonary endothelial function in anesthetized dogs.
To study the value of indexes of endothelial cell function in experimentally induced pulmonary microvascular injury, lung damage was produced in anesthetized dogs by intravenous injection of oleic acid (OA; n = 6), alpha-naphthylthiourea (ANTU; n = 5), or phorbol myristate acetate (PMA; n = 6). Angiotensin-converting enzyme (ACE) activity in serum and simultaneous measurements of serotonin (SER) and propranolol (PROP) pulmonary extraction along with several physiologic parameters were determined and compared with those obtained in a control group (n = 5) before and then at 2-h intervals for 8 h after administration of the toxic agent. ACE activity in serum showed a sustained and significant increase in the PMA and OA groups throughout the whole study period, whereas it decreased significantly at 4 h in the ANTU group. SER pulmonary uptake decreased significantly, but slightly, only in the PMA group at 8 h (-5%). At 6 and 8 h respectively, PROP extraction dropped significantly in the PMA (-11 and -13%) and OA (-13 and -19%) groups. This decrease in PROP extraction was likely to result from physiologic changes due to the development of pulmonary edema as suggested by the correlation between the changes in amine uptake and those affecting pulmonary artery pressure and total static respiratory compliance. The lack of effects on SER uptake by the lungs under these experimental conditions indicate that dissociation exists between metabolic dysfunction of pulmonary endothelial cells and fluid leakage.
Gardaz
J P
JP
Department of Surgery and Anesthesiology, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Py
P
P
Suter
P M
PM
Junod
A F
AF
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008833:Microcirculation; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011433:Propranolol / Q000493:pharmacokinetics; D011652:Pulmonary Circulation; D012701:Serotonin / Q000493:pharmacokinetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014652:Vascular Diseases / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D014655:Vascular Resistance
D009829:Oleic Acids; D019301:Oleic Acid; D012701:Serotonin; D011433:Propranolol; D007703:Peptidyl-Dipeptidase A; D013890:Thiourea; D013755:Tetradecanoylphorbol Acetate; C005277:alpha-naphthyl thiourea