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Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine.

Publication ,  Journal Article
Serebruany, VL; Solomon, SR; Edenbaum, LR; Herzog, WR; Gurbel, PA
Published in: Pharmacology
August 1996

Myocardial stunning (MS) is a transient contractile dysfunction occurring subsequent to an episode of ischemia followed by reperfusion. NPC 15669 is a leumedin, which inhibits leukocyte adhesion to the endothelium by blocking Mac-1 upregulation. The effect of NPC 15669 supplementation on the hemostasis during MS is unknown. We linked the potential changes in the hemostasis with NPC 15669 therapy during mild MS. Twelve Yorkshire swine underwent coronary artery occlusion for 8 min followed by 90 min of reperfusion. NP 15669 (10 mg/kg loading dose followed by constant infusion a 6 mg kg-1 h-1) was administered to 6 of the animals; another swine received saline and served as the controls. Concentrations of antithrombin III (AT-III), protein C, total protein S, fibronectin, endothelin 1 (ET-1) and the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1 alpha) were measured in the systemic circulation. NPC 15669 therapy was associated with diminished ET-1 (37.4%) and 6-keto-PGF1 alpha (47.1%) levels and increased fibronectin (77.6%) concentrations during MS. There were no changes in the plasma concentrations of TxB2, total protein S, protein C and AT-III in the NPC 15669 group when compared with controls. Mild MS in associated with substantial changes in the hemostatic profile. NPC 15669 administration in a swine model of MS affects certain hemostatic parameters. These data provide support for the involvement of cellular mechanisms in the pathogenesis of MS. The ability of leumedins to modulate hemostasis may have implications for their use in cardiovascular disease.

Duke Scholars

Published In

Pharmacology

DOI

ISSN

0031-7012

Publication Date

August 1996

Volume

53

Issue

2

Start / End Page

87 / 97

Location

Switzerland

Related Subject Headings

  • Up-Regulation
  • Thromboxane B2
  • Swine
  • Reperfusion Injury
  • Protein S
  • Protein C
  • Pharmacology & Pharmacy
  • Myocardial Stunning
  • Macrophage-1 Antigen
  • Leucine
 

Citation

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Serebruany, V. L., Solomon, S. R., Edenbaum, L. R., Herzog, W. R., & Gurbel, P. A. (1996). Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine. Pharmacology, 53(2), 87–97. https://doi.org/10.1159/000139419
Serebruany, V. L., S. R. Solomon, L. R. Edenbaum, W. R. Herzog, and P. A. Gurbel. “Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine.Pharmacology 53, no. 2 (August 1996): 87–97. https://doi.org/10.1159/000139419.
Serebruany VL, Solomon SR, Edenbaum LR, Herzog WR, Gurbel PA. Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine. Pharmacology. 1996 Aug;53(2):87–97.
Serebruany, V. L., et al. “Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine.Pharmacology, vol. 53, no. 2, Aug. 1996, pp. 87–97. Pubmed, doi:10.1159/000139419.
Serebruany VL, Solomon SR, Edenbaum LR, Herzog WR, Gurbel PA. Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine. Pharmacology. 1996 Aug;53(2):87–97.
Journal cover image

Published In

Pharmacology

DOI

ISSN

0031-7012

Publication Date

August 1996

Volume

53

Issue

2

Start / End Page

87 / 97

Location

Switzerland

Related Subject Headings

  • Up-Regulation
  • Thromboxane B2
  • Swine
  • Reperfusion Injury
  • Protein S
  • Protein C
  • Pharmacology & Pharmacy
  • Myocardial Stunning
  • Macrophage-1 Antigen
  • Leucine