title: Nafamostat mesilate modulates the release of platelet-activating factor during left ventricular assistance with hemofiltration in canine heart failure.
abstract: OBJECTIVE
  The enhanced generation of various chemical mediators is regarded as one of the mechanisms by which severe heart failure progresses to multiple organ failure. Platelet-activating factor is a phospholipid mediator which plays an important role in inflammatory reactions and circulatory shock. We studied the changes in platelet-activating factor levels in a canine heart failure model treated with a left ventricular assist device and hemofiltration, and assessed the effect of a protease inhibitor, nafamostat mesilate.
  
  
  METHODS
  Twenty dogs underwent multiple coronary ligations, and at 2 hours after the ligations they were maintained on left ventricular assist device support with continuous hemofiltration. The animals were divided into two groups: a nafamostat group (n = 10) that received nafamostat mesilate (2 mg/kg/hr), and a control group (n = 10) that received vehicle only.
  
  
  RESULTS
  The blood platelet-activating factor level, before coronary ligations, in the control and nafamostat groups was 2.3 +/- 0.4 and 2.0 +/- 0.7 ng/ml, respectively, and the coronary ligations had little effect on the platelet-activating factor. However, after the initiation of left ventricular assist device, the platelet-activating factor in the control group (5.6 +/- 2.2) was significantly higher (p < 0.05) than that in the nafamostat group (1.1 +/- 0.3). Nafamostat administration was also effective in controlling the increase in the blood lactate level. Hemofiltration did not change the platelet-activating factor.
  
  
  CONCLUSIONS
  We concluded that platelet-activating factor may play a critical role in the development of severe heart failure with left ventricular assistance, and nafamostat administration is likely to be beneficial in such a critical condition by suppressing the platelet-activating factor level.
authors.affiliation: First Department of Surgery, Hirosaki University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Munakata
authors.forename: Y
authors.initials: Y
authors.lastname: Ono
authors.forename: M
authors.initials: M
authors.lastname: Koyama
authors.forename: K
authors.initials: K
authors.lastname: Fukui
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001550:Benzamidines; D004285:Dogs; D006146:Guanidines / Q000494:pharmacology*; D006333:Heart Failure / Q000628:therapy*; D006353:Heart-Assist Devices; D006440:Hemofiltration; D010972:Platelet Activating Factor / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D016277:Ventricular Function, Left
chemical_list: D000991:Antithrombins; D001550:Benzamidines; D006146:Guanidines; D010972:Platelet Activating Factor; D011480:Protease Inhibitors; C032855:nafamostat