OBJECTIVE: To investigate the effects of tirofiban on the no-reflow phenomenon of acute myocardial infarction (AMI) rats received reperfusion, as well as the underlying mechanisms. METHODS: Fifty-six male Sprague-Daw...OBJECTIVE: To investigate the effects of tirofiban on the no-reflow phenomenon of acute myocardial infarction (AMI) rats received reperfusion, as well as the underlying mechanisms. METHODS: Fifty-six male Sprague-Dawley rats were randomly divided into four groups: Sham operation group (Sham), AMI/reperfusion group (AMI/R), Tirofiban group (Tiro) and Tiro+N-nitro-L-arginine group (L-NNA; an endothelial nitric oxide synthase inhibitor). To generate the animal model mimicking the no-reflow phenomenon, the rats first received occlusion of the left anterior descending coronary artery for 60 min and then followed by reperfusion for 120 min. Area of no-reflow, area at risk and area of necrosis were measured by thioflavine S, Evans blue and triphenyl tetrazolium chloride staining, respectively. Haemodynamic function was measured at the end. In the meantime, nitric oxide synthase (NOS) activity was determined by a NOS assay kit. The expression of myocardial endothelial nitric oxide synthase (eNOS) was determined by an enzyme-linked immunosorbent assay (ELISA). The expression of phosphorylated eNOS at Ser(1177) (p-eNOS Ser(1177)) and vascular endothelial-cadherin (VE-cadherin) were determined by western blot. RESULTS: Compared with AMI/R group, tirofiban significantly reduced the no-reflow area and infarct size (all P < 0.05). Tirofiban elevated eNOS activity, lessen inducible nitric oxide synthase (iNOS) activity and increased the expression of Ser(1177) phosphorylated eNOS and VE-cadherin in the ischemic myocardium (all P < 0.05). No statistical differences were found in the expression of eNOS among the four groups. Also, tirofiban improved cardiac function with significantly higher levels of left ventricular end systolic pressure, maximum change rate of left ventricular pressure rise and fall, heart rate, and lower level of left ventricular end diastolic pressure than those of the AMI/R group (all P < 0.05). Whereas, these effects of tirofiban were partially abolished by L-NNA. CONCLUSIONS: Tirofiban could reduce the size of no-reflow and infarct. A possible mechanism underlying this effect is that tirofiban could protect the structural and functional integrity of microvascular endothelium which is partially regulated by eNOS activity.展开更多
Background:Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI).However,the consistency of these effects on patients adm...Background:Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI).However,the consistency of these effects on patients administered different volumes of contrast media is unknown.Methods:In the TRACK-D trial,2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care.This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV],200-300 ml,n =712) or (high contrast volume [HCV],≥300 ml,n =220).The primary outcome was the incidence of CIAKI.The secondary outcome was a composite of death,dialysis/hemofiltration or worsened heart failure at 30 days.Results:Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1％ vs.4.4％,P =0.050) in the overall cohort and in patients with MCV (1.7％ vs.4.5％,P =0.029),whereas no benefit was observed in patients with HCV (3.4％ vs.3.9％,P =0.834).The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7％ vs.5.3％,P =0.049) in the overall cohort,but it was similar between the patients with MCV (2.0％ vs.4.2％,P =0.081) or HCV (5.1％ vs.8.8％,P =0.273).Conclusions:Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.展开更多
文摘OBJECTIVE: To investigate the effects of tirofiban on the no-reflow phenomenon of acute myocardial infarction (AMI) rats received reperfusion, as well as the underlying mechanisms. METHODS: Fifty-six male Sprague-Dawley rats were randomly divided into four groups: Sham operation group (Sham), AMI/reperfusion group (AMI/R), Tirofiban group (Tiro) and Tiro+N-nitro-L-arginine group (L-NNA; an endothelial nitric oxide synthase inhibitor). To generate the animal model mimicking the no-reflow phenomenon, the rats first received occlusion of the left anterior descending coronary artery for 60 min and then followed by reperfusion for 120 min. Area of no-reflow, area at risk and area of necrosis were measured by thioflavine S, Evans blue and triphenyl tetrazolium chloride staining, respectively. Haemodynamic function was measured at the end. In the meantime, nitric oxide synthase (NOS) activity was determined by a NOS assay kit. The expression of myocardial endothelial nitric oxide synthase (eNOS) was determined by an enzyme-linked immunosorbent assay (ELISA). The expression of phosphorylated eNOS at Ser(1177) (p-eNOS Ser(1177)) and vascular endothelial-cadherin (VE-cadherin) were determined by western blot. RESULTS: Compared with AMI/R group, tirofiban significantly reduced the no-reflow area and infarct size (all P < 0.05). Tirofiban elevated eNOS activity, lessen inducible nitric oxide synthase (iNOS) activity and increased the expression of Ser(1177) phosphorylated eNOS and VE-cadherin in the ischemic myocardium (all P < 0.05). No statistical differences were found in the expression of eNOS among the four groups. Also, tirofiban improved cardiac function with significantly higher levels of left ventricular end systolic pressure, maximum change rate of left ventricular pressure rise and fall, heart rate, and lower level of left ventricular end diastolic pressure than those of the AMI/R group (all P < 0.05). Whereas, these effects of tirofiban were partially abolished by L-NNA. CONCLUSIONS: Tirofiban could reduce the size of no-reflow and infarct. A possible mechanism underlying this effect is that tirofiban could protect the structural and functional integrity of microvascular endothelium which is partially regulated by eNOS activity.
文摘Background:Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI).However,the consistency of these effects on patients administered different volumes of contrast media is unknown.Methods:In the TRACK-D trial,2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care.This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV],200-300 ml,n =712) or (high contrast volume [HCV],≥300 ml,n =220).The primary outcome was the incidence of CIAKI.The secondary outcome was a composite of death,dialysis/hemofiltration or worsened heart failure at 30 days.Results:Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1％ vs.4.4％,P =0.050) in the overall cohort and in patients with MCV (1.7％ vs.4.5％,P =0.029),whereas no benefit was observed in patients with HCV (3.4％ vs.3.9％,P =0.834).The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7％ vs.5.3％,P =0.049) in the overall cohort,but it was similar between the patients with MCV (2.0％ vs.4.2％,P =0.081) or HCV (5.1％ vs.8.8％,P =0.273).Conclusions:Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.
