Rationale and design of a randomized controlled trial: The effect of intensive lipid-lowering therapy with PCSK9 inhibitor on endothelial-coverage of stent strut after percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS): Optical coherence tomography (OCT) study (PIECES-OCT study).

Background: For the patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) for at least 1 year is recommended in the guidelines to minimize the risk of stent thrombosis. Persistently uncovered stent strut means delayed neointima formation and extend the window of time in which the stent is prone to thrombosis. Previous studies showed that statins could improve post-stenting strut endothelial coverage for patients undergoing PCI. However, there are lack of evidences on whether early initiation of proprotein convertase subtilisin/Kexin type 9 monoclonal antibody (PCSK9mAb) after PCI in ACS patients can further improve the rate of stent strut coverage on the background of oral lipid-lowering therapy (LLT). Methods: This is a single-center, randomized trial to enroll 36 patients undergoing PCI with a clinical diagnosis of non-ST-segment elevation ACS. The baseline level of low-density lipoprotein cholesterol (LDL-C) of these patients are between 1.4 mmol/L and 3.4 mmol/L. Patients will be assigned to intensive lipid-lowering therapy (LLT) with PCSK9mAb group and conventional LLT without PCSK9mAb group for 12 weeks in a clinical follow-up setting according to 1: 1 randomization. the rate of stent strut endothelial coverage by optical coherence tomography (OCT) examination at 12 weeks after enrollment between the groups will be compared. Conclusion: This will be the first study to investigate changes in the rate of stent strut endothelial coverage under intensive LLT with PCSK9mAb by OCT examination in ACS patients undergoing PCI. The finding of this study will provide clinical evidence for future research about the hypothesis of a novel strategy of "intensive LLT (PCSK9mAb + statin ± ezetimibe) combined with shortened DAPT duration" for ACS patients undergoing PCI.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: ChiCTR2200063395.

[Analysis of VOCs Emission Characteristics and Emission Reduction Potential of Typical Industries in Jinan, China].

Based on the air pollutant emission inventory of Jinan in 2020, the VOCs emission status and existing problems of typical industries including the chemical industry, industrial coating, printing, and furniture manufacturing were investigated and analyzed, and two emission reduction scenarios were designed to estimate the emission reduction potential according to the enterprise scales and the end-of-pipe treatment techniques. The results showed that the VOCs emissions of the typical industries from large to small were the chemical industry(7947.92 t), industrial coating(2383.29 t), printing(792.87 t), and furniture manufacturing(143.79 t). The chemical industry and industrial painting were dominated by large enterprises, accounting for 46.45% and 50.89% of VOCs emissions, whereas printing and furniture manufacturing were dominated by medium-sized enterprises, accounting for 51.76% and 42.37% of VOCs emissions, respectively. The end-of-pipe treatment was dominated by a single inefficient treatment technique, and the utilization rate of efficient treatment techniques such as combustion techniques and combination techniques was only 7.46%. The on-site investigation reported some problems in some enterprises, including incomplete source substitution, inadequate management of fugitive emissions, and unsuitable end-of-pipe treatment facilities. Therefore, VOCs emissions of typical industries had a certain reduction potential. Under the two designed emission reduction scenarios, the chemical industry had the greatest emission reduction potential, with emission reduction rates of 69.58%-84.99%, and the emission reduction rates of industrial coating, printing, and furniture manufacturing industries were 26.98%-34.74%, 36.96%-59.74%, and 8.55%-40.45%, respectively. Among the four industries, large and medium-sized enterprises had greater emission reduction potential, with average emission reduction rates of 70.00% and 44.23%, respectively. Under the scenario of a higher emission reduction target, the average emission reduction rates of small and micro enterprises were greatly increased, reaching 87.49% and 79.65%, respectively. The results of this study could provide scientific basis for developing VOCs governance in typical industries and enterprises.

The Effects of Sacubitril/Valsartan Compared to Olmesartan on the Blood Pressure and Glucolipid Metabolism in DM Patients with Primary Hypertension.

PURPOSE: Given the beneficial effects of sacubitril/valsartan on blood pressure generally, this study investigates its antihypertension effects in diabetes mellitus (DM) patients with primary hypertension specifically, and the effect of sacubitril/valsartan on glycolipid metabolism. METHODS: We conducted a randomized, open-label, active-controlled study to compare the antihypertension effects of sacubitril/valsartan in DM individuals with primary hypertension. The primary end point was reduction in mean systolic blood pressure (SBP) from baseline with sacubitril/valsartan vs. olmesartan at week 8. The secondary endpoints included the changes in diastolic blood pressure (DBP), daytime SBP/DBP, nighttime SBP/DBP, BP achievement (office sitting BP < 130/80 mmHg), and lipid profile. The trial was registered with chictr.org.cn (ChiCTR2200066428) on Dec 22, 2022. RESULTS: A total of 124 patients were included in the final analysis. SBP decreased to a greater extent in the sacubitril/valsartan group from baseline to 8 weeks [between-treatment difference: 3.51 mm Hg, 95% confidence interval (95% CI) 0.41 to 6.62 mm Hg, P = 0.03]. Furthermore, more patients achieved the blood pressure goal with sacubitril/valasartan (74.60% vs. 54.70%, P = 0.03). Multiple logistical regression analysis showed that sacubitril/valsartan was associated with BP achievement [odds ratio (OR) 0.33, 95% CI 0.14-0.73, P = 0.007], but the difference in SBP, DBP, day time SBP/DBP, and night time SBP/DBP reduction did not approach statistical significance. HbA1C1, total cholesterol, and low-density lipoprotein-cholesterol were lower than baseline in both groups (P < 0.05); however, there was no difference in the effects on glucose and lipid metabolism from sacubitril/valsartan compared to olmesartan. CONCLUSIONS: Sacubitril/valsartan not only provided superior BP reduction compared to olmesartan, it did so without adverse effects on glycemic control and lipid parameters in DM patients with primary hypertension.

Analysis of Factors Influencing Air Quality in Different Periods during COVID-19: A Case Study of Tangshan, China.

This study aimed to analyze the main factors influencing air quality in Tangshan during COVID-19, covering three different periods: the COVID-19 period, the Level I response period, and the Spring Festival period. Comparative analysis and the difference-in-differences (DID) method were used to explore differences in air quality between different stages of the epidemic and different years. During the COVID-19 period, the air quality index (AQI) and the concentrations of six conventional air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3-8h) decreased significantly compared to 2017-2019. For the Level I response period, the reduction in AQI caused by COVID-19 control measures were 29.07%, 31.43%, and 20.04% in February, March, and April of 2020, respectively. During the Spring Festival, the concentrations of the six pollutants were significantly higher than those in 2019 and 2021, which may be related to heavy pollution events caused by unfavorable meteorological conditions and regional transport. As for the further improvement in air quality, it is necessary to take strict measures to prevent and control air pollution while paying attention to meteorological factors.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Effect of pre-procedural statin therapy on myocardial no-reflow following percutaneous coronary intervention: a meta analysis.

BACKGROUND: Successful revascularization of coronary artery disease, especially ST-elevation myocardial infarction (STEMI), does not always mean optimal myocardial reperfusion in a portion of patients because of no-reflow phenomenon. We hypothesized that statins might attenuate the incidence of myocardial no-reflow when used before percutaneous coronary intervention (PCI). The purpose of this study was to summarize the evidence of pre-procedural statin therapy to reduce myocardial no-reflow after PCI. METHODS: We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases from inception to October 2012 for clinical trials that examined statin therapy before PCI. We required that studies initiated statins before PCI and reported myocardial no-reflow. A DerSimonian-Laird model was used to construct random-effects summary risk ratios. RESULTS: In all, 7 studies with 3086 patients met our selection criteria. The use of pre-procedural statins significantly reduced post-procedural no-reflow by 4.2% in all PCI patients (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.35 to 0.90, P = 0.016), and attenuated by 5.0% in non-STEMI patients (RR 0.41, 95% CI 0.18 to 0.94, P = 0.035). This benefit was mainly observed in the early or acute intensive statin therapy populations (RR 0.43, 95% CI 0.26 to 0.71, P = 0.001). CONCLUSIONS: Acute intensive statin therapy before PCI significantly reduces the hazard of post-procedural no-reflow phenomenon. The routine use of statins before PCI should be considered.

The cardioprotection of simvastatin in reperfused swine hearts relates to the inhibition of myocardial edema by modulating aquaporins via the PKA pathway.

BACKGROUND AND OBJECTIVE: Myocardial edema plays a role in myocardial no-reflow and infarction during ischemia and reperfusion. The effects of statins against no-reflow and infarction may relate to the inhibition of myocardial edema. The current study investigated the role of protein kinase A (PKA) in statin-reduced myocardial edema in reperfused swine hearts. METHODS AND RESULTS: Minipigs were treated with simvastatin (SIM, 2mg/kg), SIM+H-89 (a PKA inhibitor, 1.0 µg/kg/min), or H-89 alone 1h before 90-min ischemia and 3-h reperfusion or sham operation. Ischemia or ischemia-reperfusion induced severe myocardial edema, PKA activation, and up-regulation of aquaporin-1, -4, -8, and -9 in the reflow and no-reflow myocardium. SIM pretreatment reduced the sizes of no-reflow and infarct areas by 18.5% and 11.1% (P<0.01), decreased water content in the left ventricle, reflow and no-reflow myocardium by 1.4%, 5.3%, and 4.3% (P<0.05), inhibited cardiomyocytes swelling in the reflow and no-reflow areas by 19.8% and 13.1% (P<0.01), suppressed mitochondrial water accumulation in the reflow and no-reflow areas by 49.0% and 35.9% (P<0.01), increased PKA activity (P<0.01), and blocked the up-regulation of aquaporin-1, -4, -8, and -9 in the reflow and no-reflow myocardium. However, these beneficial effects of SIM were partially abolished by inhibiting PKA with H-89. CONCLUSIONS: The cardioprotective effects of acute SIM therapy against myocardial no-reflow and infarction relate to the reduction of myocardial edema by suppressing the expression of aquaporin-1, -4, -8, and -9 in a partially PKA-dependent manner.

Chronic pretreatment of metformin is associated with the reduction of the no-reflow phenomenon in patients with diabetes mellitus after primary angioplasty for acute myocardial infarction.

INTRODUCTION: Metformin is one of the most commonly prescribed antihyperglycemic agents for the treatment of type 2 diabetes. However, little is known about the effect of metformin on no-reflow in diabetic patients. AIM: In this study, we investigated retrospectively whether chronic pretreatment with metformin was associated with no-reflow in diabetic patients who underwent primary coronary intervention for acute myocardial infarction (AMI). RESULTS: A total of 154 consecutive diabetic patients who underwent primary angioplasty for a first ST-segment elevation myocardial infarction were studied. No-reflow was defined as a final TIMI flow of ≤2 or final TIMI flow of 3 with a myocardial blush grade of <2. The no-reflow phenomenon was found in 53 of 154 patients. There were no significant differences in clinical characteristics between the patients with and without metformin pretreatment. However, the 65 patients receiving chronic metformin treatment before admission had lower incidence of the no-reflow than those without it (4.2 and 14.6%, P < 0.05). Multivariable logistic regression analysis revealed that absence of metformin pretreatment was a significant predictor of the no-reflow along with high-burden thrombus, ejection fraction on admission and anterior AMI. CONCLUSION: These results suggested that chronic pretreatment with metformin may be associated with the reduction of the no-reflow phenomenon in patients with diabetes mellitus after primary angioplasty for AMI.

Phosphorylation of endothelial NOS contributes to simvastatin protection against myocardial no-reflow and infarction in reperfused swine hearts: partially via the PKA signaling pathway.

AIM: The cholesterol-lowering drugs statins could enhance the activities of endothelial nitric oxide synthase (eNOS) and protect myocardium during ischemia and reperfusion. The aim of this study was to examine whether protein kinase A (PKA) was involved in statin-mediated eNOS phosphorylation and cardioprotection. METHODS: 6-Month-old Chinese minipigs (20-30 kg) underwent a 1.5-h occlusion and 3-h reperfusion of the left anterior descending coronary artery (LAD). In the sham group, the LAD was encircled by a suture but not occluded. Hemodynamic and cardiac function was monitored using a polygraph. Plasma activity of creatine kinase and the tissue activities of PKA and NOS were measured spectrophotometrically. p-CREB, eNOS and p-eNOS levels were detected using Western blotting. Sizes of the area at risk, the area of no-reflow and the area of necrosis were measured morphologically. RESULTS: Pretreatment of the animals with simvastatin (SIM, 2 mg/kg, po) before reperfusion significantly decreased the plasma activity of creatine kinase, an index of myocardial necrosis, and reduced the no-reflow size (from 50.4%±2.4% to 36.1%±2.1%, P<0.01) and the infarct size (from 79.0%±2.7% to 64.1%±4.5%, P<0.01). SIM significantly increased the activities of PKA and constitutive NOS, and increased Ser(133) p-CREB protein, Ser(1179) p-eNOS, and Ser(635) p-eNOS in ischemic myocardium. Intravenous infusion of the PKA inhibitor H-89 (1 µg·kg(-1)·min(-1)) partially abrogated the SIM-induced cardioprotection and eNOS phosphorylation. In contrast, intravenous infusion of the eNOS inhibitor L-NNA (10 mg·kg(-1)) completely abrogated the SIM-induced cardioprotection and eNOS phosphorylation during ischemia and reperfusion, but did not affect the activity of PKA. CONCLUSION: Pretreatment with a single dose of SIM 2.5 h before reperfusion attenuates myocardial no-reflow and infarction through increasing eNOS phosphorylation at Ser(1179) and Ser(635) that was partially mediated via the PKA signaling pathway.

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.

[Ischemic preconditioning attenuates myocardial no-reflow and reperfusion injury after revascularization of acute myocardial infarction by reducing myocardial edema via the protein kinase A pathway].

OBJECTIVE: Myocardial edema plays an important role in the development of myocardial no-reflow and reperfusion injury after the revascularization of acute myocardial infarction (AMI). The present study investigated whether the effect of ischemic preconditioning (IPC) against myocardial no-reflow and reperfusion injury was related to the reduction of myocardial edema through the protein kinase A (PKA) pathway. METHODS: Twenty-four minipigs were randomized into sham, AMI, IPC, and IPC + H-89 (PKA inhibitor, 1.0 µg · kg(-1) · min(-1)) groups. The area of no-reflow (ANR), area of necrosis (AN), and water content in left ventricle and ischemic-myocardium and non-ischemic area were determined by pathological studies. Microvascular permeability was determined by FITC-labeled dextran staining. Cardiomyocyte cross-sectional area (CSA) and mitochondria cross-sectional area (MSA) were evaluated by histological analysis. Myocardial expression of aquaporins (AQPs) was detected by Western blot. RESULTS: Compared with the MI group, the sizes of no-reflow and infarct were reduced by 31.9% and 46.6% in the IPC group (all P < 0.01), water content was decreased by 5.7% and 4.6% in the reflow and no-reflow myocardium of the IPC group (all P < 0.05), microvascular permeability and cardiomyocytes swelling in the reflow area were inhibited by 29.8% and 21.3% in the IPC group (all P < 0.01), mitochondrial water accumulation in the reflow and no-reflow areas of the IPC group were suppressed by 45.5% and 34.8% respectively (all P < 0.01), and the expression of aquaporin-4, -8, and -9 in the reflow and no-reflow myocardium were blocked in the IPC group. However, these beneficial effects of IPC were partially abolished in the IPC + H-89 group. CONCLUSIONS: The cardioprotective effects of IPC against no-reflow and reperfusion injury is partly related to the reduction of myocardial edema by inhibition of microvascular permeability and aquaporins up-regulation via PKA pathway.

No-reflow disrupts the expression and distribution of connexin 43 in a swine model.

INTRODUCTION AND OBJECTIVES: Ischemia and ischemia/reperfusion can dephosphorylate and redistribute connexin 43 (Cx43). But it is unknown whether no-reflow phenomenon has an effect on the expression and distribution of Cx43 after acute infarction and reperfusion. METHODS: 21 open-chest pigs were divided into three groups. Left anterior descending artery (LAD) occlusion for 90 min before 180 min of reperfusion was made in ischemia/reperfusion group. The pigs in ischemia groups were either subjected to LAD ligation for 90 min or for 270 min. No-reflow and risk regions were determined pathologically by dye staining. Cx43 expression was measured by western blotting and quantitative RT-PCR analysis. Cx43 spatial distribution was shown by immunofluorescence examination. RESULTS: The content of phosphorylated and mRNA of Cx43 were higher in reflow region than in the no-reflow or sustained ischemic region. The distribution of Cx43 was also altered in no-reflow region. CONCLUSIONS: There are some differences in synthesis, expression and distribution of myocardial Cx43 at microvascular level after ischemia/reperfusion. Cx43 is partially rephosphorylated with reperfusion only in the reflow myocardium.

Tongxinluo reduces myocardial no-reflow and ischemia-reperfusion injury by stimulating the phosphorylation of eNOS via the PKA pathway.

The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 µg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism.

BACKGROUND: The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. METHODS: Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively. RESULTS: Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. CONCLUSIONS: Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.

[Effects of tongxinluo on mini-swine vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction].

OBJECTIVE: To assess the effects of tongxinluo on vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction. METHODS: Forty mini-swines were divided into five groups randomly, sham group, control group, low dose (0.1 g/kg), medium dose (0.2 g/kg) and high dose (0.4 g/kg) groups of Tongxinluo. It was administered at 2 hours pre-reperfusion. Animals except in sham group were subjected to 1.5 hour of coronary occlusion followed by 3 hours of reperfusion. Content of VE-cadherin, beta-catenin, matrix metalloproteinase (MMP)-2 and 9 in myocardium were evaluated; no-reflow area was examined with myocardial contrast echocardiography (MCE) at 1.5 hour of AMI and 3 hours of reperfusion. RESULTS: (1) Compared with that of normal myocardium, content of VE-cadherin and beta-catenin decreased in reperfusion and no-reflow myocardium while MMP-2 and 9 increased significantly (all P < 0.05); (2) Compared with that of control group, a high dose of Tongxinluo could increase significantly the content of VE-cadherin in both reperfusion and no-reflow myocardium, (22.2 +/- 3.2)% vs (32.0 +/- 3.9)% and (14.5 +/- 2.8)% vs (28.3 +/- 2.2)% respectively, beta-catenin, (20.5 +/- 3.5)% vs (27.3 +/- 2.9)% and (13.3 +/- 2.1)% vs (20.6 +/- 2.4)%, while reduce MMP-2, (48.3 +/- 4.1)% vs (29.4 +/- 3.5)% and (57.3 +/- 4.3)% vs (38.2 +/- 4.0)% respectively, MMP-9, (55.6 +/- 4.0)% vs (34.3 +/- 3.5)% and (62.4 +/- 4.8)% vs (44.4 +/- 4.1)%, all P < 0.05; (3) Compared with that of control group, a high dose of Tongxinluo could reduce significantly both no-reflow area, (6.6 +/- 1.7) cm2 vs (4.7 +/- 1.5) cm2, P < 0.05, and percentage (90.8 +/- 3.8)% vs (71.4 +/- 4.1)%, P < 0.05, at 3 hours of reperfusion. CONCLUSION: A high dose of tongxinluo could effectively maintain the integrity of vascular endothelium and attenuate no-reflow area in early reperfusion of acute myocardial infarction.

The effect of statins on the no-reflow phenomenon: an observational study in patients with hyperglycemia before primary angioplasty.

BACKGROUND: An association between admission plasma glucose levels and an increased risk of no-reflow has been well documented. Although HMG-CoA reductase inhibitor (statin) therapy can reduce no-reflow, little is known about its effect on no-reflow in patients with hyperglycemia. In the present study, we investigated whether pretreatment with a statin could reduce no-reflow in patients with hyperglycemia, who underwent primary coronary intervention for acute myocardial infarction (AMI). METHODS: A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. Blood glucose and creatinine kinase levels were measured on admission. All patients underwent 2-dimensional echocardiography and electrocardiographic analysis just after admission. No-reflow was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade <3. Hyperglycemia was defined as a blood glucose level >or=10 mmol/L. Statin administration prior to admission was determined by detailed interview or information in the medical records. RESULTS: Hyperglycemia was diagnosed in 154 patients on admission. The no-reflow phenomenon was found in 31 of the 154 patients with hyperglycemia. The incidence of no-reflow was significantly greater in patients with hyperglycemia compared with no hyperglycemia. A multivariable logistic regression analysis showed that hyperglycemia on admission was an independent predictor of no-reflow. Among the 154 patients with hyperglycemia, there were no significant differences in baseline clinical characteristics between patients who received statin pretreatment and those who did not; however, hyperlipidemia occurred in a greater number of the patients who did not receive statin pretreatment. The 40 patients with hyperglycemia who received statins before admission had a lower incidence of no-reflow than those who did not receive statin pretreatment (5% and 25.4%; p < 0.05). Multivariable logistic regression analysis revealed that absence of statin pretreatment was a significant predictor of no-reflow in patients with hyperglycemia, along with ejection fraction on admission, initial TIMI 0 flow, number of Q waves, and anterior AMI. CONCLUSION: The results of our study show that pretreatment with statins could attenuate no-reflow after AMI in patients with acute hyperglycemia.

Remote periconditioning reduces myocardial no-reflow by the activation of K ATP 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.

Intravenous adenosine reduces myocardial no-reflow by decreasing endothelin-1 via activation of the ATP-sensitive K+ channel.

UNLABELLED: It has been verified that adenosine can attenuate myocardial no-reflow. However, the effects of adenosine on adenosine triphosphate-sensitive K+ (KATP) channel and endothelin-1 (ET-1) are unknown. METHODS: Forty mini-swines were randomized into 5 study groups: 8 in the control group, 8 in the adenosine pretreatment group, 8 in the glibenclamide (K(ATP) channel blocker)-treated group, 8 in the adenosine and glibenclamide-pretreated group and 8 in the sham-operated group. An acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by a one-hour reperfusion. RESULTS: Compared with the control group, adenosine significantly decreased the area of no-reflow (myocardial contrast echocardiography: from 78.5 +/- 4.5% to 20.7 +/- 4.1%, pathological means: from 82.3 +/- 1.9% to 21.5 +/- 4.3% of ligation area, respectively; all P < 0.01), reduced necrosis size from 98.5 +/- 1.3% to 75 +/- 4.7% of ligation area, P < 0.05). It also decreased plasma ET-1 and myocardial tissue ET-1. However, glibenclamide abrogated the protective effect of adenosine. CONCLUSION: The beneficial effect of adenosine on myocardial no-reflow could be due to its effect on ET-1 via the activation of K(ATP) channel.

Effect of statins on contrast-induced nephropathy in patients with acute myocardial infarction treated with primary angioplasty.

We investigated whether pretreatment with statin may prevent contrast-induced nephropathy in patients who underwent primary coronary intervention for acute myocardial infarction (AMI). A total of 279 consecutive patients who underwent successful primary angioplasty for a first AMI were studied. Contrast-induced nephropathy was defined as an increase in serum creatinine of > or =5 mg/dL after the primary PCI. 56 patients receiving statin treatment before admission had lower incidence of the contrast-induced nephropathy than those without it (7.1% and 20.6%, P<0.01). Multivariable logistic regression analysis revealed that absence of statin pre-treatment was a significant predictor of the reperfusion arrhythmia along with anterior AMI, baseline creatinine value, time-to-reperfusion, higher volume of the contrast agent. Pre-treatment with statin could reduce the contrast-induced nephropathy after primary coronary intervention in patients with AMI.

Effect of statin therapy on reperfusion arrhythmia in patients who underwent successful primary angioplasty.

BACKGROUND: In animal models, pretreatment with statin can prevent reperfusion arrhythmia. In the observational study, we investigated whether pretreatment with statin may prevent reperfusion arrhythmia in patients who underwent primary coronary intervention for acute myocardial infarction (AMI). METHOD AND RESULTS: A total of 226 consecutive patients who underwent successful primary angioplasty for a first AMI were studied. Reperfusion arrhythmias were defined as all arrhythmias that occurred within 2 h after successful primary angioplasty. The reperfusion arrhythmia was found in 130 of 226 patients. There were no significant differences in clinical characteristics between the patients with and without statin pretreatment. However, the 41 patients receiving statin treatment before admission had lower incidence of the reperfusion arrhythmia than those without it (19.5% and 65.9%, P < 0.01). Multivariable logistic regression analysis revealed that absence of statin pre-treatment was a significant predictor of the reperfusion arrhythmia along with absence of pre-infarction angina and inferior AMI. CONCLUSION: Pre-treatment with statin could reduce the reperfusion arrhythmias after acute myocardial infarction in human.