Ischemic and endotoxin pre-conditioning reduce lung reperfusion injury-induced surfactant alterations.
BACKGROUND
Pulmonary ischemia/reperfusion injury represents a common clinical phenomenon after lung transplantation, pulmonary embolism, and cardiac surgery with extracorporeal circulation. We investigated the influence of ischemic and endotoxin pre-conditioning on gas exchange and surfactant properties in a canine model of ischemia/reperfusion injury.


METHODS
Twenty-six foxhounds underwent 3 hours of warm ischemia of the left lung, followed by 8 hours of reperfusion. Ischemic pre-conditioning was performed for either 5 minutes (IPC-5) or by 2 10-minute ischemic periods (IPC-10), before ischemia. For endotoxin pre-conditioning, dogs were pre-treated by a daily intravenous application of increasing amounts of endotoxin for 6 days. No pre-conditioning was performed in the controls. Bronchoalveolar lavage was performed before ischemia/reperfusion injury (baseline) and after the 8-hour reperfusion period in the non-injured right and in the reperfused left lung. Bronchoalveolar lavage fluids were analyzed for the phospholipid-protein ratio, the content of large surfactant aggregates, the phospholipid and neutral lipid profile, the surfactant protein (SP) content, and for biophysical activity.


RESULTS
Severe surfactant alterations were observed in the ischemia/reperfusion-injured left lung, with increased protein concentrations and depressed concentrations of large surface aggregates, SP-B, dipalmitoylated phosphatidylcholine, and phosphatidylglycerol. Endotoxin pre-conditioning and IPC-5 were both capable of greatly preventing the ischemia/reperfusion injury-related deterioration of surfactant properties. IPC-10 exerted no effects. Endotoxin pre-conditioning and IPC-5, but not IPC-10, also prevented loss of gas exchange.


CONCLUSIONS
Ischemic and endotoxin pre-conditioning may protect against impairment of gas exchange in ischemia/reperfusion injury by restoring physiological surfactant properties.
Markart
Philipp
P
Department of Internal Medicine, Med. Klinik II, Justus-Liebig University, Giessen, Germany.
Schmidt
Reinhold
R
Ruppert
Clemens
C
Höres
Christina
C
Silber
Rolf E
RE
Börgermann
Jochen
J
Günther
Andreas
A
Friedrich
Ivar
I
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004285:Dogs; D004731:Endotoxins / Q000008:administration & dosage*; D004926:Escherichia coli; D006801:Humans; D019194:Ischemic Preconditioning; D008055:Lipids / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008171:Lung Diseases / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D010713:Phosphatidylcholines / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D011659:Pulmonary Gas Exchange; D037661:Pulmonary Surfactant-Associated Proteins / Q000032:analysis*; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
D004731:Endotoxins; D008055:Lipids; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D010743:Phospholipids; D037661:Pulmonary Surfactant-Associated Proteins