Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine
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Updated: Nov 3, 2026
Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures
Published on: March 12, 2018
V L Serebruany1, S R Solomon, L R Edenbaum
1Heart Associates Research and Education Foundation, Union Memorial Hospital, Baltimore, MD 21218, USA.
Abstract:
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.
Insights
NPC 15669, a leumedin, modulated hemostasis during myocardial stunning (MS) in swine. This drug reduced endothelin-1 and prostacyclin levels, while increasing fibronectin, suggesting cellular mechanisms in MS pathogenesis.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Hemostasis Research
Background:
- Myocardial stunning (MS) involves transient contractile dysfunction after ischemia-reperfusion.
- NPC 15669 is a leumedin that inhibits leukocyte adhesion by blocking Mac-1.
- The impact of NPC 15669 on hemostasis during MS remains uncharacterized.
Purpose of the Study:
- To investigate the effects of NPC 15669 on hemostatic parameters during mild myocardial stunning (MS).
- To explore the potential role of cellular mechanisms in MS pathogenesis through leumedin therapy.
Main Methods:
- A swine model of mild MS was established using coronary artery occlusion and reperfusion.
- NPC 15669 was administered to one group, while a control group received saline.
- Plasma concentrations of antithrombin III, protein C, protein S, fibronectin, endothelin 1, thromboxane B2, and 6-keto-prostaglandin F1 alpha were measured.
Main Results:
- NPC 15669 therapy significantly reduced endothelin-1 (37.4%) and 6-keto-prostaglandin F1 alpha (47.1%) levels.
- Fibronectin concentrations were notably increased (77.6%) in the NPC 15669 group.
- No significant changes were observed in thromboxane B2, protein C, protein S, or antithrombin III levels compared to controls.
Conclusions:
- Mild MS is associated with significant alterations in the hemostatic profile.
- NPC 15669 administration impacts specific hemostatic parameters in a swine model of MS.
- Leumedins' ability to modulate hemostasis may offer therapeutic potential in cardiovascular diseases.
