Early recovery of microvascular perfusion induced by t-PA in combination with abciximab or eptifibatide during postischemic reperfusion.

Abstract

BACKGROUND:

GPIIb/IIIa inhibitors abciximab and eptifibatide have been shown to inhibit platelet aggregation in ischemic heart disease. Our aim was to test the efficacy of abiciximab (Reo Pro) or eptifibatide (Integrilin) alone or in combination with plasminogen activator (t-PA) in an experimental model of ischemia reperfusion (I/R) in hamster cheek pouch microcirculation visualized by fluorescence microscopy. Hamsters were treated with saline, or abiciximab or eptifibatide or these drugs combined with t-PA infused intravenously 10 minutes before ischemia and through reperfusion. We measured the microvessel diameter changes, the arteriolar red blood cell (RBC) velocity, the increase in permeability, the perfused capillary length (PCL), and the platelet and leukocyte adhesion on microvessels.

RESULTS:

I/R elicited large increases in the platelet and leukocyte adhesion and a decrease in microvascular perfusion. These responses were significantly attenuated by abiciximab or eptifibatide (PCL:70 and 65% at 5-10 mins of reperfusion and 85 and 87% at 30 mins of reperfusion, respectively, p < 0.001) while t-PA combined with abiciximab or eptifibatide, was more effective and microvascular perfusion recovered immediately after postischemic reperfusion.

CONCLUSIONS:

Platelets are crucial in I/R injury, as shown by the treatment with abicixmab or eptifibatide, which decreased platelet aggregation in microvessels, and also decreased leukocyte adhesion in venules. Arterial vasoconstriction, decreased arterial RBC velocity and alterations in the endothelial barrier with increased permeability delayed the complete restoration of blood flow, while t-PA combined with inhibition of platelet aggregation speeded up the capillary perfusion after reperfusion.

• Authors: Silva Bertuglia, Andrea Giusti
• Journal: BMC cardiovascular disorders (BMC Cardiovasc Disord) Vol. 2 Pg. 10 (Jun 19 2002) ISSN: 1471-2261 [Electronic] England
• PMID: 12086588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin Fab Fragments
• Peptides
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• Plasminogen Activators
• Eptifibatide
• Abciximab

Topics

• Abciximab
• Animals
• Antibodies, Monoclonal (pharmacology)
• Arterioles (drug effects, physiopathology)
• Capillaries (drug effects, physiopathology)
• Cheek
• Cricetinae
• Drug Evaluation, Preclinical
• Drug Therapy, Combination
• Eptifibatide
• Immunoglobulin Fab Fragments (pharmacology)
• Leukocytes (drug effects)
• Microcirculation (drug effects, physiology)
• Peptides (pharmacology)
• Plasminogen Activators (pharmacology)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (pharmacology)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Reperfusion Injury (drug therapy, physiopathology)
• Venules (drug effects, physiopathology)