Platelet Glycoprotein IIb/IIIa Inhibitor Tirofiban Ameliorates Cardiac Reperfusion Injury

Abstract

There are many published articles on the effects of the antithrombolytic function of platelet glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa inhibitors) in myocardial infarction. However, few studies have explored the effects and optimal concentration of tirofibans in diminishing the extent of myocardial reperfusion injury (RI).Rats received 120 minutes of coronary ligation and 180 minutes of reperfusion. The rats were then divided into 7 groups based on the concentration of tirofiban administered intravenously 30 minutes prior to coronary reperfusion to the end of reperfusion. The ratio of myocardial necrotic area to area at risk (AAR), and myocardial malondialdehyde (MDA) and plasma myeloperoxidase (MPO) activities were measured. The apoptotic index (AI) was the percentage of myocytes positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) out of all myocytes stained by 4', 6-diamidino-2-phenylindole (DAPI).The ratio of myocardial necrotic area to AAR significantly decreased in all tirofiban subgroups. The MDA activity for tirofiban concentrations of 2 and 5 ug/kg/minute showed a slight reduction. MPO activity was significantly decreased at a tirofiban concentration of 2 ug/kg/minute. The AI was significantly decreased at a tirofiban concentration of ≥ 0.4 ug/kg/minute.The results indicate that a tirofiban can significantly ameliorate the cardiac RI and myocyte apoptosis in rats.

Cyclosporin A Protects H9c2 Cells Against Chemical Hypoxia-Induced Injury via Inhibition of MAPK Signaling Pathway

“…Hypoxia/ischemia induced oxidative stress injuries by scavenging ROS and lipid peroxidation production of MDA. 10) SOD is one of the principal enzymes that scavenge free radicals. 11) GSH, which is a major cellular antioxidant, is not only the immediate donor of electrons to neutralize H 2 O 2 and lipoperoxide, but also a scavenger of oxygen and nitrogen-based free radicals.…”

“…H9c2 cells were seeded on culture slides (5 × 10 5 cells/well) for 24 hours and then the CoCl 2 -induced cell injury protocol was performed. CsA (10,30, and 50 ng/mL) was added to the plates. The cells were incubated for an additional 24 hours at 37°C.…”

Thromboinflammatory Functions of Platelets in Ischemia–Reperfusion Injury and Its Dysregulation in Diabetes

“…No reflow is partially reduced by infusion of GPIIb-IIIa antagonists, 54 implicating microvascular platelet thrombi. In further studies, cardiac infarct size in a rat model of reperfusion injury was decreased in a dose-dependent manner by treatment with tirofiban, 55 which coincided with decreases in cardiomyocyte apoptosis and neutrophil infiltration. In humans, abciximab administration promotes improved microvascular perfusion, 56 culprit vessel patency, 57,58 and decreased platelet-leukocyte interactions.…”

Short-term efficacy and safety of three different antiplatelet regimens in diabetic patients treated with primary percutaneous coronary intervention: a randomised study

“…GP IIb/IIIa receptor inhibitors act on a final unique pathway, competitively occupying the GP IIb/IIIa receptors and preventing the binding of fibrinogen with such receptors, thus quickly and almost completely inhibiting platelet aggregation [5,[15][16][17][18][19]. These agents can take effect 5 min after intravenous administration, and the 30-min IPA is greater than 93%; hence, the platelet inhibitory effects of these drugs are faster and more direct.…”