Modulation of pulmonary vascular resistance and edema formation by short-term infusion of a 10% fish oil emulsion.
BACKGROUND
The aim of this study was to investigate whether the pulmonary response to inflammatory stimulation, resulting in increased vascular resistance and permeability, could be attenuated by short-term infusion of triglycerides containing omega-3 fatty acids. With the concept of altering the composition of membrane phospholipids in such a manner that stimulation resulted in the release of less vasoconstrictive and permeability-enhancing metabolites of eicosapentaenoic acid instead of those of arachidonic acid (AA), the parenteral application of a lipid emulsion prepared from fish oil (Omegavenös) was tested in comparison with a soy oil preparation (Lipovenös).


METHODS
Isolated lungs from anesthetized rabbits were ventilated and recirculatingly perfused (200 ml/min) with 200 ml cell-free buffer solution to which either 2 ml saline (controls, n = 6), 2 ml Lipovenös 10% (n = 6) or 2 ml Omegavenös 10% (n = 6) were added. To study the possible metabolic alterations in states of an enhanced AA turnover, lungs of each group were stimulated with smaller doses of A23187 (10(-8) M) during the 180-min lipid perfusion period, followed by a 10 times higher calcium ionophore A23187 (10(-7) M) challenge after washing out the lipids by exchange of perfusion fluid. Pulmonary artery pressure (PAP) and the lung weight gain indicating edema formation were monitored, and eicosanoids were analyzed in samples of the perfusate.


RESULTS
Upon A23187 injection lung weight gain and PAP increase were significantly reduced (50%) in Omegavenös-perfused lungs in comparison with controls and Lipovenös treatment. The vascular reactions were accompanied by a shifting from LTC4 to LTC5 during and after Omegavenös perfusion.


CONCLUSIONS
The data demonstrate that omega-3 fatty acids seem to be incorporated into the phospholipid pool of the pulmonary tissue, even after short-term infusion (3 h) resulting in an attenuated pressure reaction and edema formation due to an altered spectrum of metabolites in the case of inflammatory stimulation.
Koch
T
T
Institut für Anaesthesiologie und Operative Intensivmedizin, Klinikum der Stadt Mannheim, Fakultät für Klinische Medizin, Universität Heidelberg.
Duncker
H P
HP
Klein
A
A
Schlotzer
E
E
Peskar
B M
BM
van Ackern
K
K
Neuhof
H
H
D000209:Acute-Phase Proteins / Q000502:physiology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015633:Extravascular Lung Water / Q000187:drug effects* / Q000502:physiology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D013024:Soybean Oil / Q000494:pharmacology; D014280:Triglycerides / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D000209:Acute-Phase Proteins; D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D014280:Triglycerides; D000001:Calcimycin; D013024:Soybean Oil