Effect of Intralipid on hypoxic and angiotensin-II induced pulmonary vasoconstriction in the isolated rat lung.
OBJECTIVE
Lipid infusions are reported to cause hypoxemia by increasing intrapulmonary shunt fraction. However, the mechanism by which they worsen gas exchange is unknown. We hypothesized that a reduction in hypoxic pulmonary vasoconstriction, caused by lipid infusion, could be the cause of increased shunt.


METHODS
A prospective, controlled laboratory study.


METHODS
A postgraduate teaching hospital laboratory.


METHODS
Male Wistar rats weighing 250 to 300 g.


METHODS
Four separate series of experiments were performed: a) The pulmonary vasopressor response to angiotensin-II was compared before and after adding either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). b) The pulmonary vasopressor response to hypoxia (FIO2 of 0.3) was compared before and after either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). c) 1 microM of indomethacin was added before either 0.9% sodium chloride (control n = 5) or Intralipid (n = 5) and the hypoxic pulmonary vasoconstriction response was compared. d) 10(-3) M L-monomethyl-n-arginine was added before 20 microL of Intralipid and the hypoxic pulmonary vasoconstriction response was compared (n = 5).


RESULTS
Changes in pulmonary arterial pressure were measured before and after interventions. Intralipid reduced the angiotensin-II pressor response by 36 +/- 3% (p = .005) and the hypoxic pulmonary vasoconstriction response by 50 +/- 2% (p = .0003). This action was not blocked by pretreatment with either indomethacin or L-monomethyl-n-arginine.


CONCLUSIONS
Intralipid reduces the hypoxic pulmonary vasoconstriction response in the isolated, blood perfused rat lung. This action is nonspecific, as shown by a similar reduction in the pulmonary pressor response to angiotensin-II. Pharmacologic blockade of prostaglandin release, by indomethacin, and nitric oxide release, by L-monomethyl-n-arginine did not prevent the reduction in hypoxic pulmonary vasoconstriction, thereby suggesting that neither agent mediates the lipid-induced change in pulmonary vasoreactivity.
Baudouin
S V
SV
Department of Anaesthesia and Intensive Care, National Heart and Lung Institute, Royal Brompton and National Heart and Lung Hospital, London, UK.
Messent
M
M
Evans
T W
TW
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D005217:Fat Emulsions, Intravenous; D011453:Prostaglandins; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin