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Nafamostat mesilate modulates the release of platelet-activating factor during left ventricular assistance with hemofiltration in canine heart failure

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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.

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Authors and Affiliations

  1. First Department of Surgery, Hirosaki University School of Medicine, 5-Zaifucho, 036-8216, Hirosaki, Japan

    Mamoru Munakata, Yuichi Ono, Masayuki Koyama, Kozo Fukui & Sohei Suzuki

  2. Departmet of Pathological Physiology, Institute of Neurological Disease, Hirosaki University School of Medicine, Hirosaki, Japan

    Masayuki Koyama & Kei Satoh

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  1. Mamoru Munakata
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  2. Yuichi Ono
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  3. Masayuki Koyama
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  4. Kozo Fukui
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  5. Kei Satoh
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  6. Sohei Suzuki
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Munakata, M., Ono, Y., Koyama, M. et al. Nafamostat mesilate modulates the release of platelet-activating factor during left ventricular assistance with hemofiltration in canine heart failure. Jpn J Thorac Caridovasc Surg 48, 106–111 (2000). https://doi.org/10.1007/BF03218100

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  • DOI: https://doi.org/10.1007/BF03218100

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