ABSTRACT
We aimed to explore the different protective effects of tirofiban on myocardial ischemia-reperfusion (IR) injury in New Zealand white rabbits by comparing the results from different administration methods. Fifty New Zealand white rabbits were randomly divided into a sham group (group A, n = 10) and four IR groups (group B, IR group with injection of physiological saline; group C, tirofiban administered through marginal ear vein after reperfusion; group D, tirofiban injected through coronary ostia before reperfusion; group E, tirofiban injected through coronary artery after blood flow restoration; all n = 10). Myocardial IR injury models were prepared in IR groups. An automatic biochemical analyzer (HITACHI 7020, Japan) was applied for testing serum creatine kinase-MB levels. The myeloperoxidase activity, malondialdehyde levels, nitric oxide synthase activity, and nitric oxide (NO) volume were detected 180 minutes after reperfusion. The myocardial apoptosis was identified using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling technique, and the protein expressions of B-cell lymphoma-2, Bcl-2 associated X, and aquaporin-1 were measured through Western blot. The highest and lowest ST-segment resolution among the IR groups was observed in groups E and B, respectively. The creatine kinase-MB levels at 60, 120, and 180 minutes in group E was greatly decreased than in groups B, C, and D. Compared with the sham group, the IR groups demonstrated evidently elevated myeloperoxidase activity, malondialdehyde levels, inducible NOS activity, NO volume, myocardial apoptotic index, and aquaporin-1 expressions; among the IR groups, these indicators were increased and decreased most in groups B and E, respectively. The B-cell lymphoma-2/Bcl-2 associated X ratio in the IR groups were evidently higher than the sham group, with the highest and lowest rate in groups E and B, respectively. Tirofiban injection through coronary artery after blood flow restoration has a better protective effect against myocardial IR injury than tirofiban administration through coronary ostia before reperfusion and tirofiban injection through the auricular vein after reperfusion.
Subject(s)
Fibrinolytic Agents/administration & dosage , Myocardial Reperfusion Injury/drug therapy , Tyrosine/analogs & derivatives , Animals , Apoptosis/drug effects , Coronary Circulation/drug effects , Coronary Vessels/metabolism , Disease Models, Animal , Fibrinolytic Agents/pharmacology , In Situ Nick-End Labeling , Injections , Myocardial Reperfusion Injury/complications , Nitric Oxide/metabolism , Rabbits , Random Allocation , Tirofiban , Tyrosine/administration & dosage , Tyrosine/pharmacologyABSTRACT
OBJECTIVES: The aim of this study is to compare preoperative and postoperative conditions of GMP-140 concentration, the aggregation and activation of platelets in congenital heart disease patients undergoing transcatheter closure of atrial septal defects (ASDs) or ventricular septal defects (VSDs), and the appropriate dose of aspirin of patients after transcatheter closure. MATERIALS AND METHODS: Thirty-two consecutive patients with ASD (n=16) and VSD (n=16), as shown on transthoracic echocardiography and right heart catheter examination, were treated with a percutaneous catheter occlusion. The patients comprised 13 males and 19 females with a mean age of 25.6±9.15. Patients were randomly assigned into two groups within half an hour after ASD or VSD occlusion. Group A cases were treated with 3 mg/kg/day enteric-coated aspirin tablets for 6 months, while patients in group B received 5 mg/kg/day enteric-coated aspirin tablets for 6 months. RESULTS: The rates of platelet aggregation (PAG) in the immediate postoperative ASD/VSD occlusion were significantly higher than those in the preoperative ASD/VSD occlusion (adenosine diphosphate [ADP]-induced PAG: 64.98%±7.65% vs. 86.33%±6.54%, p<0.05; arachidonic acid [AA]-induced PAG: 62.92%±9.11% vs. 86.96%±6.90%, p<0.05, respectively). After treatment with aspirin, the GMP-140 levels presented a clearly defined downward trend in the immediate postoperative period (3 mg/kg/day aspirin: 18.30±3.42 vs. 13.37±1.80, p<0.05; 5 mg/kg/day aspirin: 18.30±3.42 vs. 13.41±1.60, p<0.05), but no obvious difference was observed considering the GMP-140 levels in the 4 days after occlusion (all p>0.05). CONCLUSION: Our study showed that the GMP-140 serum level and PAG were increased after ASD and VSD occlusion, and patients may have a trend of decreased GMP-140 serum levels after the ASD or VSD occlusion surgeries after the treatment with aspirin. Daily oral administration of 3 and 5 mg/kg/day aspirin can induce a significant decrease in PAG of patients after VSD/ASD occlusion.