Nafamostat preserves neutrophil deformability and reduces microaggregate formation during simulated extracorporeal circulation.
BACKGROUND
Initial sequestration of activated neutrophils and platelet microaggregates in capillaries are responsible for the inflammatory response associated with cardiopulmonary bypass. The study assesses the inhibitory effects of nafamostat mesilate on neutrophil and platelet activation, and on the neutrophil deformability change and microaggregate formation during simulated extracorporeal circulation.


METHODS
Fresh heparinized human blood was recirculated for 120 minutes in a membrane oxygenator and a roller pump with and without nafamostat (1.0 mg bolus plus 8.0 mg/h infusion; n = 10 for each group). Neutrophil and platelet counts and platelet aggregation were measured. CD11b, L-selectin, and cytoplasmic F-actin of neutrophils were measured by flow cytometry. The microchannel transit time of whole blood was measured as a marker of neutrophil deformability and microaggregate formation. Neutrophil elastase and complement C4d were measured using enzyme immunoassay.


RESULTS
Nafamostat preserved platelet counts and inhibited platelet aggregation. Nafamostat significantly reduced neutrophil elastase release at 120 minutes of recirculation, and F-actin expression at 30 and 60 minutes. The drug did not modulate the changes of CD11b, L-selectin, or C4d. Whole blood filterability was significantly preserved by nafamostat at 30 and 120 minutes.


CONCLUSIONS
Nafamostat preserves blood filterability during recirculation, possibly by suppression of F-actin expression and platelet activation. Nafamostat may reduce neutrophil sequestration and microaggregate formation in the microcirculation during cardiopulmonary bypass.
Hiramatsu
Yuji
Y
Department of Cardiovascular Surgery, University of Tsukuba, Tsukuba, Japan. yuji3@md.tsukuba.ac.jp
Homma
Satoshi
S
Sato
Yukio
Y
Sato
Shoko
S
Matsuzaki
Kanji
K
Shigeta
Osamu
O
Sakakibara
Yuzuru
Y
D001550:Benzamidines; D039481:CD11b Antigen / Q000097:blood; D005112:Extracorporeal Circulation; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D019041:L-Selectin / Q000097:blood; D019272:Leukocyte Elastase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D001550:Benzamidines; D039481:CD11b Antigen; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D019041:L-Selectin; D019272:Leukocyte Elastase; C032855:nafamostat