Shi-Jie You

Pretreatment with simvastatin reduces myocardial no‐reflow by opening mitochondrial KATP channel

Simvastatin, a cholesterol‐lowering agent, can protect against endothelial dysfunction. However, the effects of simvastatin treatment on the restoration of blood flow to ischemic myocardium are not known. This study sought to assess such effects of simvastatin on an experimental model of myocardial no‐reflow and to explore possible mechanisms.

Different effects of tirofiban and aspirin plus clopidogrel on myocardial no-reflow in a mini-swine model of acute myocardial infarction and reperfusion

Objective: To compare the effects of an aspirin–clopidogrel combination with those of the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no-reflow, nitric oxide concentration and activity of nitric oxide synthase (NOS) isoforms in a mini-swine model of acute myocardial infarction and reperfusion. Methods: Area of no-reflow was determined by both myocardial contrast echocardiography and pathological means in 40 mini-swine randomly assigned to five study groups: eight controls, eight pretreated with aspirin–clopidogrel combination for three days, eight given an intravenous infusion of tirofiban, eight treated with ischaemic preconditioning and eight sham operated. The acute myocardial infarction and reperfusion model was created with 3 h occlusion of the left anterior descending coronary artery followed by 1 h reperfusion. Results: Compared with the control group, tirofiban significantly decreased the area of no-reflow assessed echocardiographically and pathologically, from 78.5% to 22.8% and 82.3% to 23.2%, respectively (both p < 0.01), and increased blood nitric oxide concentration (p < 0.05), enhanced constitutive NOS activity from 0.51 to 0.81 U/mg protein and mRNA expression from 0.47% to 0.66%, but decreased inducible NOS activity from 0.76 to 0.41 U/mg protein and mRNA expression from 0.54% to 0.39% in reflow myocardium (all p < 0.05–0.01). In contrast, the aspirin–clopidogrel combination did not significantly modify the above parameters (all p > 0.05) except for decreasing inducible NOS activity from 0.76 to 0.39 U/mg protein (p < 0.01) and mRNA expression from 0.54% to 0.40% (p < 0.05). Conclusions: Tirofiban is very effective in attenuating myocardial no-reflow; in contrast, aspirin–clopidogrel combination is totally ineffective. These findings also support the concept that endothelial protection, apart from platelet inhibition, contributes to the beneficial effect of tirofiban on myocardial no-reflow.

Follow-up by cardiac magnetic resonance imaging in patients with hypertrophic cardiomyopathy who underwent percutaneous ventricular septal ablation.

To evaluate myocardial infarction and describe the early to mid-term changes induced by percutaneous ventricular septal ablation (PVSA) in symptomatic patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging. Cardiac magnetic resonance imaging was performed before and 1 week and 1 year after PVSA in 52 patients. The relation between the infarction size and other factors was determined. At 1 week after PVSA, regional hyperenhancement was visualized in the basal interventricular septum in all patients. The mean infarction size was 29.5 ± 15.9 g. The infarction size correlated well with the ethanol volume. The left ventricular myocardial mass decreased significantly from 196.1 ± 65.9 g at baseline to 183.4 ± 63.6 g 1 week after PVSA (p <0.001) and 164.1 ± 60.9 g within the 1-year follow-up period (p <0.001). In conclusion, cardiac magnetic resonance imaging allowed a detailed evaluation of the size and location of septal myocardial infarction induced by PVSA. The left ventricular myocardial mass decreased significantly during the follow-up period.

An Angiographic Tool for Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention : The RESOLVE Score System (Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion)

OBJECTIVES The purpose of this study was to establish a scoring system to evaluate the risk of side branch (SB) occlusion in patients undergoing coronary bifurcation intervention. BACKGROUND The risk of SB occlusion is the most important consideration affecting the selection of an optimal intervention strategy. METHODS A total of 1,545 consecutive patients undergoing percutaneous coronary intervention for bifurcation lesions (1,601 lesions treated with a single stent technique or main vessel [MV] stenting first strategy) were studied. A total of 1,200 lesions were used to construct the risk model and score system, and 401 lesions were used to validate the model. A multivariable risk score (RESOLVE [Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion]) was constructed with incremental weights attributed to each component variable according to its estimated coefficients. SB occlusion after MV stenting was defined as any decrease in Thrombolysis in Myocardial Infarction flow grade or absence of flow in SB after MV stenting. RESULTS SB occlusion occurred in 118 (7.37%) of 1,601 bifurcation lesions. In multivariable analyses, 6 variables were independently associated with the risk of SB occlusion (model C-statistic = 0.80 [95% confidence interval: 0.75 to 0.85] with good calibration). For the 401 lesions included in the validation cohort, the RESOLVE score had a C-statistic of 0.77 (95% confidence interval: 0.69 to 0.86), with good calibration. SB occlusion rates in the validation cohort increased significantly across different risk groups, from 0.0% in the low-risk group, to 3.8% in the intermediate-risk group, and to 19.8% in the high-risk group (p < 0.001). CONCLUSIONS The RESOLVE score, a novel angiographic risk stratification tool, can help identify patients at risk for SB occlusion during bifurcation intervention.

Post‐infarction treatment with simvastatin reduces myocardial no‐reflow by opening of the KATP channel

Simvastatin can prevent cardiac remodelling after myocardial infarction, though the exact mechanisms are uncertain. Myocardial no‐reflow is associated with progressive cardiac remodelling. However, it remains unknown whether post‐infarction treatment with simvastatin can also reduce myocardial no‐reflow for which suppression of adenosine triphosphate‐sensitive K+ (KATP) channel opening is an important mechanism.

Remote periconditioning reduces myocardial no-reflow by the activation of KATP channel via inhibition of Rho-kinase

UNLABELLED Remote periconditioning is induced by brief cycles of ischemia and reperfusion of a remote organ applied during sustained myocardial ischemia. It remains unknown whether the remote periconditioning reduces myocardial no-reflow. The adenosine triphosphate-sensitive potassium (K(ATP)) channel opening and inhibition of Rho-kinase may be the important mechanism of protection against myocardial no-reflow. Therefore, this study was sought to assess the effect of remote periconditioning on myocardial no-reflow and explore the possible mechanism. METHODS Coronary ligation area and area of no-reflow were determined with pathological means in 58 mini-swines randomized into 7 study groups: 9 controls, 8 in remote periconditioning, 8 in hydroxyfasudil (a specific inhibitor of Rho-kinase)-treated, 9 in glibenclamide (K(ATP) channel blocker)-treated, 8 in remote periconditioning and glibenclamide, 8 in hydroxyfasudil and glibenclamide and 8 sham-operated. The ischemia and reperfusion model was created with 3 h of left anterior descending artery occlusion followed by 2 h of reperfusion. RESULTS Compared with the control group, remote periconditioning decreased Rho-kinase activity (P<0.01), increased coronary blood volume (P<0.05), decreased area of no-reflow (from 82.3+/-3.9% to 45.5+/-5.7% of ligation area, P<0.01) and reduced necrosis size (from 98.5+/-1.3% to 74.7+/-6.3% of ligation area, P<0.05). Hydroxyfasudil had the same effect on the above parameters as remote periconditioning. Glibenclamide abrogated the effect of remote periconditioning or hydroxyfasudil on area of no-reflow and necrosis area, but not Rho-kinase activity. CONCLUSION Remote periconditioning can reduce myocardial no-reflow after ischemia and reperfusion. This beneficial effect could be due to its activation of K(ATP) channel via inhibition of Rho-kinase.

Pretreatment with fosinopril or valsartan reduces myocardial no-reflow after acute myocardial infarction and reperfusion.

BackgroundBoth fosinopril and valsartan are effective in protecting endothelial function. We hypothesized that they may also reduce myocardial no-reflow. In addition, suppression of adenosine triphosphate-sensitive K+ (KATP) channel opening is an important mechanism for myocardial no-reflow. Therefore, this study sought to assess the effect of fosinopril and valsartan on myocardial no-reflow and explore the possible mechanism. MethodsCoronary ligation area and the area of no-reflow were determined with both myocardial contrast echocardiography in vivo and pathological means in 56 mini-swine randomized into seven study groups: eight in control, eight in fosinopril-pretreated (1 mg/kg/day) for 3 days, eight in fosinopril and glibenclamide (KATP channel blocker)-pretreated, eight in valsartan-pretreated (2 mg/kg/day) for 3 days, eight in valsartan and glibenclamide-pretreated, eight in glibenclamide-treated and eight in sham-operated. An acute myocardial infarction and reperfusion model was created with a 3-h occlusion of the coronary artery followed by a 2-h reperfusion. The levels of KATP channel proteins (SUR2, Kir6.1, and Kir6.2) in the reflow and no-reflow myocardium were quantified by Western blotting. ResultsCompared with the control group, both fosinopril and valsartan significantly improved ventricular function, decreased area of no-reflow (myocardial contrast echocardiography: from 78.5±4.5 to 24.5±2.7 and 24.3±3.6%, pathological means: from 82.3±1.9 to 25.2±3.2 and 24.9±4.4% of ligation area, respectively; all P<0.01), reduced necrosis size from 98.5±1.3 to 88.9±3.6 and 89.1±3.1% of ligation area, respectively (both P<0.05). They also increased the levels of SUR2 and Kir6.2 (P<0.01), but had no effect on the level of Kir6.1 (P>0.05). A combination of fosinopril or valsartan with glibenclamide significantly increased area of no-reflow (P<0.05) and decreased the levels of SUR2 and Kir6.2 (P<0.01). ConclusionsPretreatment with fosinopril or valsartan can reduce myocardial no-reflow. This beneficial effect is due to activation of the KATP channel.

How bifurcation angle impacts the fate of side branch after main vessel stenting: A retrospective analysis of 1,200 consecutive bifurcation lesions in a single center

We aimed to investigate the effect of bifurcation angle (BA) on side branch (SB) occlusion after main vessel (MV) stenting. Background: BA is thought to impact the risk of SB occlusion in coronary bifurcation patients undergoing percutaneous coronary intervention (PCI).

PKA-mediated eNOS phosphorylation in the protection of ischemic preconditioning against no-reflow.

OBJECTIVE To investigate whether ischemic preconditioning (IP) can reduce myocardial no-reflow by activating endothelial (e-) nitric oxide synthase (NOS) via the protein kinase A (PKA) pathway. METHODS AND RESULTS In a 90-min ischemia and 3-h reperfusion model, minipigs were assigned into sham, ischemia-reperfusion (IR), IR+IP, IR+IP+L-NNA (an eNOS inhibitor, 10mg·kg(-1)), IR+IP+H-89 (a PKA inhibitor, 1.0μg·kg(-1)·min(-1)), IR+L-NNA, and IR+H-89 groups. IP pretreatment improved cardiac function and coronary blood flow, decreased the activities of creatine kinase by 36.6% after 90 min of ischemia and by 32.8% after 3 h of reperfusion (P<0.05), reduced the no-reflow areas from 49.9% to 11.0% (P<0.01), and attenuated the infarct size from 78.2% to 35.4% (P<0.01). IP stimulated myocardial PKA activities and the expression of PKA and Ser(133) phosphorylated (p-) cAMP response element-binding protein (CREB) in the reflow and no-reflow myocardium, and enhanced the activities of constitutive NOS and the phosphorylation of eNOS at Ser(1179) and Ser(635) in the no-reflow myocardium. IP suppressed the expression of tumor necrosis factor-α and P-selectin, and attenuated cardiomyocytes apoptosis by regulating the expression of Bcl-2 and caspase-3 in the reflow and no-reflow myocardium. The eNOS inhibitor L-NNA completely canceled these beneficial effects of IP without any influence on PKA activity, whereas the PKA inhibitor H-89 partially blocked the IP cardioprotective effects and eNOS phosphorylation at the same time. CONCLUSION IP attenuates myocardial no-reflow and infarction after ischemia and reperfusion by activating the phosphorylation of eNOS at Ser(1179) and Ser(635) in a partly PKA-dependent manner.

Drug-eluting stents for the treatment of ostial coronary lesions: comparison of sirolimus-eluting stent with paclitaxel-eluting stent.

BackgroundTreatment of ostial coronary lesions represents a challenge for interventional cardiologists. The efficacy of drug-eluting stents (DES) has been demonstrated as improving the outcomes of patients in a few studies. It is not known, however, which DES, sirolimus-eluting stent (SES) versus paclitaxel-eluting stent (PES), is superior for the treatment of ostial lesions. MethodsIn this retrospective study, 95 consecutive patients with de-novo ostial lesions underwent coronary SES (n=47, lesions=48) or PES implantation (n=45, lesions=47), and quantitative coronary analysis was performed at the time of stent implantation and subsequently at 8 months post stenting. Ostial lesion was defined as ≥50% diameter stenosis rising within 3 mm of either left anterior descending coronary artery or left circumflex artery or right coronary artery measured by quantitative coronary analysis. Major adverse cardiac events including death, thrombosis, nonfatal myocardial infarction, and target lesion revascularization were compared between the two groups. ResultsBaseline clinical and angiographic characteristics were well balanced between the two groups. At 8 months clinical and angiographic follow-up, overall major adverse cardiac events and target lesion revascularization rates were similar in both groups (6.4 vs. 11.2%, P=0.184; 4.3 vs. 8.9%, P=0.170, respectively). The in-stent and in-segment restenosis were, however, significantly higher in PES group compared with SES group (15.5 vs. 0%, P=0.001; 22.2 vs. 4.3%, P=0.003). Similarly, the late loss in both in-stent and in-segment was significantly higher in the PES group than in SES group (0.65±0.67 vs. 0.16±0.18 mm; 0.68±0.65 vs. 0.15±0.12 mm; P<0.001, respectively). ConclusionIn this small sample-size, nonrandomized, and nonprospective study, the data indicated that implantation of DES appears safe and effective for the treatment of patients with de-novo ostial coronary lesions, but SES implantation showed more favorable results in respect of restenosis compared with PES implantation.