Prevention of ischemia/reperfusion-induced pulmonary dysfunction after cardiopulmonary bypass with terminal leukocyte-depleted lung reperfusion.
OBJECTIVE
Pulmonary ischemia and reperfusion during routine open heart surgery with cardiopulmonary bypass can lead to pulmonary dysfunction and vasoconstriction, resulting in a high morbidity and mortality. We investigated whether ischemia/reperfusion-induced pulmonary dysfunction after full-flow cardiopulmonary bypass could be prevented by the infusion of leukocyte-depleted hypoxemic blood during the early phase of reperfusion (terminal leukocyte-depleted lung reperfusion) and whether the benefits of this method were nullified by using hyperoxemic blood for reperfusion.


METHODS
Twenty-one neonatal piglets underwent 180 minutes of full-flow cardiopulmonary bypass with pulmonary artery occlusion, followed by reperfusion. The piglets were divided into 3 groups of 7 animals. In group I, uncontrolled reperfusion was achieved by unclamping the pulmonary artery. In contrast, pulmonary reperfusion was done with leukocyte-depleted hyperoxemic blood in group II or with leukocyte-depleted hypoxemic blood in group III for 15 minutes at a flow rate of 10 mL/min/kg before pulmonary artery unclamping. Then the animals were monitored for 120 minutes to evaluate post-cardiopulmonary bypass pulmonary function.


RESULTS
Group I developed pulmonary dysfunction that was characterized by an increased alveolar-arterial oxygen difference (204 + or - 57.7 mm Hg), pulmonary vasoconstriction, and decreased static lung compliance. Terminal leukocyte-depleted lung reperfusion attenuated post-cardiopulmonary bypass pulmonary dysfunction and vasoconstriction when hypoxemic blood was used for reperfusion (alveolar-arterial oxygen difference, 162 + or - 61.0 mm Hg). In contrast, no benefit of terminal leukocyte-depleted lung reperfusion was detected after reperfusion with hyperoxemic blood (alveolar-arterial oxygen difference, 207 + or - 60.8 mm Hg).


CONCLUSIONS
Reperfusion with leukocyte-depleted hypoxemic blood has a protective effect against ischemia/reperfusion-induced pulmonary dysfunction by reducing endothelial damage, cytokine release, and leukocyte activation.
Kagawa
Hiroshi
H
Department of Cardiac Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan. hkagawa@jikei.ac.jp
Morita
Kiyozo
K
Nagahori
Ryuichi
R
Shinohara
Gen
G
Kinouchi
Katsushi
K
Hashimoto
Kazuhiro
K
D000818:Animals; D000831:Animals, Newborn; D002315:Cardiopulmonary Bypass; D019332:Endothelin-1 / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis; D007958:Leukocyte Count; D047589:Leukocyte Reduction Procedures; D007962:Leukocytes; D008168:Lung / Q000098:blood supply* / Q000201:enzymology / Q000502:physiology; D009589:Nitrogen Oxides / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D015424:Reperfusion / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014655:Vascular Resistance / Q000502:physiology
D019332:Endothelin-1; D015850:Interleukin-6; D009589:Nitrogen Oxides; D009195:Peroxidase