No-reflow phenomenon in stroke patients: A systematic literature review and meta-analysis of clinical data.

BACKGROUND: The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion. AIM: The aim of this analysis was to summarize the available clinical evidence on no-reflow in patients with acute ischemic stroke. METHODS: A systematic literature review and a meta-analysis of clinical data on definition, rates, and impact of the no-reflow phenomenon after reperfusion therapy was carried out. A predefined research strategy was formulated according to the Population, Intervention, Comparison, and Outcome (PICO) model and was used to screen for articles in PubMed, MEDLINE, and Embase up to 8 September 2022. Whenever possible, quantitative data were summarized using a random-effects model. RESULTS: Thirteen studies with a total of 719 patients were included in the final analysis. Most studies (n = 10/13) used variations of the Thrombolysis in Cerebral Infarction scale to evaluate macrovascular reperfusion, whereas microvascular reperfusion and no-reflow were mostly assessed on perfusion maps (n = 9/13). In one-third of stroke patients with successful macrovascular reperfusion (29%, 95% confidence interval (CI), 21-37%), the no-reflow phenomenon was observed. Pooled analysis showed that no-reflow was consistently associated with reduced rates of functional independence (odds ratio (OR), 0.21, 95% CI, 0.15-0.31). CONCLUSION: The definition of no-reflow varied substantially across studies, but it appears to be a common phenomenon. Some of the no-reflow cases may simply represent remaining vessel occlusions, and it remains unclear whether no-reflow is an epiphenomenon of the infarcted parenchyma or causes infarction. Future studies should focus on standardizing the definition of no-reflow with more consistent definitions of successful macrovascular reperfusion and experimental set-ups that could detect the causality of the observed findings.

Effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: Evidence of therapy for dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) is limited. This study was performed to compare the effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation. METHODS: This retrospective study enrolled 597 consecutive patients with STEMI who underwent pPCI in 3 centers from June 2016 to December 2019. Dysfunctional coronary circulation was defined by the thrombolysis in myocardial infarction (TIMI) grade and the TIMI myocardial perfusion grade (TMPG). Logistic regression analysis was used to evaluate the impact of different statin types on dysfunctional coronary circulation. RESULTS: The incidence of TIMI no/slow reflow did not differ between the two groups, but the incidence of TMPG no/slow reflow was significantly lower in the atorvastatin than rosuvastatin group (44.58% vs. 57.69%, respectively). After multivariate adjustment, the odds ratio with 95% confidence interval of rosuvastatin was 1.72 (1.17-2.52) for after pretreatment TMPG no/slow reflow and 1.73 (1.16-2.58) for after stenting TMPG no/slow reflow. Atorvastatin and rosuvastatin showed no significant differences in clinical outcomes during hospitalization. CONCLUSIONS: Compared with rosuvastatin, atorvastatin was associated with better coronary microcirculatory perfusion in patients with STEMI who underwent pPCI.

Efficacy and safety of intracoronary epinephrine for the management of the no-reflow phenomenon following percutaneous coronary interventions: a systematic-review study.

BACKGROUND: Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon. OBJECTIVES: To assess the efficacy and safety of intracoronary (IC) epinephrine in the management of no-reflow phenomenon following percutaneous coronary intervention (PCI), either as first-line treatment or after the failure of conventional agents. DESIGN: Systematic review. DATA SOURCES AND METHODS: PubMed and Scopus databases were systematically searched up to 28 May 2022, with additional manual search on the Google Scholar and review of the reference lists of the relevant studies to identify all published studies. Cohort studies, case series, and interventional studies written in English which evaluated the efficacy and safety of IC epinephrine in patients with no-flow phenomenon were included in our review. RESULTS: Six of the 646 articles identified in the initial search met our inclusion criteria. IC epinephrine was used either as a first-line treatment [two randomized clinical trials (RCTs)] or after the failure of conventional agents (two cohort studies and two case series) for restoring the coronary flow, mainly after primary PCI. As first-line therapy, IC epinephrine successfully restored coronary flow in over 90% of patients in both RCTs, which significantly outperformed IC adenosine (78%) but lagged behind combination of verapamil and tirofiban (100%) in this regard. In the refractory no-flow phenomenon, successful reperfusion [thrombolysis in myocardial infarction (TIMI) flow grade = 3] was achieved in three out of four patients after the administration of IC epinephrine based on the results from both case series. Their findings were confirmed by a recent cohort study that further compared IC epinephrine with IC adenosine and found significant differences between them in terms of efficacy [% TIMI flow grade 3: (69.1% versus 52.7%, respectively; p value = 0.04)] and 1-year major adverse cardiac event (MACE) outcomes (11.3% versus 26.7%, respectively; p value ⩽ 0.01). Overall, malignant ventricular arrhythmias were reported in none of the patients treated with IC epinephrine. CONCLUSION: Results from available evidence suggest that IC epinephrine might be an effective and safe agent in managing the no-reflow phenomenon.

Intracoronary epinephrine versus adenosine in the management of refractory no-reflow phenomenon: a single-center retrospective cohort study.

BACKGROUND: The no-reflow phenomenon is associated with a considerable reduction in myocardial salvage in patients with ST elevation myocardial infarction (STEMI) treated by primary percutaneous intervention (PCI). There has been no head-to-head comparison of intra-coronary epinephrine to adenosine in the management of no-reflow phenomenon. OBJECTIVES: Evaluate the short- and long-term efficacy and safety of using intracoronary epinephrine versus adenosine for management of the catastrophic no-reflow phenomenon that may occur during primary PCI. DESIGN: Retrospective cohort. SETTING: Single center in Egypt. PATIENTS AND METHODS: The study included STEMI patients who developed refractory no-reflow phenomenon during primary PCI after failure of conventional treatments and received either intracoronary epinephrine or adenosine. MAIN OUTCOME MEASURES: No-reflow management measured through improvement of thrombolysis in myocardial infarction grade (TIMI flow), myocardial blush grade, TIMI frame count and major adverse cardiovascular events (MACE) at 1-year follow up. SAMPLE SIZE: 156 patients with refractory no-reflow phenomenon during primary PCI. RESULTS: Successful reperfusion was achieved in 74 of 81 (91.4%) of patients who received epinephrine and in 65 of 75 (86.7%) who received adenosine (P<.05). Fifty-six of 81 patients (69.1%) achieved TIMI III flow after epinephrine administration versus 39 of 75 patients (52.7%) in the adenosine group (P=.04). The incidence of heart failure after 1 year of follow up was lower in the epinephrine group compared to the adenosine group (6.3% vs. 19.2%, P<.017). MACE after 1 year of follow up was lower in patients who received epinephrine compared to those who received adenosine (11.3 % Vs. 26.7 %, P<.01). CONCLUSION: During primary PCI, intracoronary epinephrine is as effective as adenosine in successful management of refractory no-reflow phenomenon with a more favorable long-term prognosis compared to adenosine. LIMITATIONS: Retrospective design. CONFLICT OF INTEREST: None.

Slow Coronary Flow: Pathophysiology, Clinical Implications, and Therapeutic Management.

Coronary slow flow (CSF) is an angiographic phenomenon with specific epidemiologic characteristics, associated clinical presentation, and prognosis. Although patients with CSF are diagnosed as having "normal coronary arteries," it seems appropriate to consider CSF as a distinct disease entity requiring specific treatment. The patient with CSF is usually male, smoker, obese, with a constellation of risk factors suggestive of metabolic syndrome. Unstable angina is the most common clinical presentation, with recurrent episodes of chest pain at rest associated with electrocardiographic changes often requiring readmission and reevaluation. Regarding definition and diagnosis, interventionists should first exclude possible "secondary" causes of CSF, use objective means for definition and then differentiate from other similar conditions such as microvascular angina. Although the phenomenon is generally benign, patients with CSF are severely symptomatic with recurrent episodes of chest pain and poor quality of life. Furthermore, acute presentation of the phenomenon is commonly life-threatening with ventricular tachyarrhythmias, conduction abnormalities, or cardiogenic shock. Acute treatment of CSF includes, but is not restricted to, intracoronary infusion of dipyridamole, adenosine, or atropine. Chronic management of patients with CSF encompasses dipyridamole, diltiazem, nebivolol, telmisartan, and/or atorvastatin associated with amelioration of angina symptoms, improved quality of life, and good prognosis.

Tongmai Yangxin pill reduces myocardial No-reflow via endothelium-dependent NO-cGMP signaling by activation of the cAMP/PKA pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease. Previous studies have confirmed that TMYX can improve vascular endothelial function in patients with coronary heart disease by upregulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels remains unclear. AIM OF THE STUDY: This study aimed to reveal whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels. The underlying cAMP/PKA and NO-cGMP signaling pathway-dependent mechanism is also explored. MATERIALS AND METHODS: The left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish the NR model. TMYX (4.0 g/kg) was orally administered throughout the experiment. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were used to evaluate the NR and ischemic areas. Pathological changes in the myocardium were assessed by hematoxylin-eosin staining. An automated biochemical analyzer and kit were used to detect the activities of myocardial enzymes and myocardial oxidants, including CK, CK-MB, LDH, reactive oxygen species, superoxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins related to the cAMP/PKA and NO/cGMP signaling pathways were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was used to detect coronary artery diastolic function in vitro. RESULTS: TMYX elevated the EF, FS, LVOT peak, LVPWd and LVPWs values, decreased the LVIDd, LVIDs, LV-mass, IVSd, and LV Vols values, demonstrating cardio-protective effects, and reduced the NR and ischemic areas. Pathological staining showed that TMYX could significantly reduce inflammatory cell number and interstitial edema. The activities of CK, LDH, and MDA were reduced, NO activity was increased, and oxidative stress was suppressed after treatment with TMYX. TMYX not only enhanced the expression of Gs-α, AC, PKA, and eNOS but also increased the expression of sGC and PKG. Furthermore, TMYX treatment significantly decreased ROCK expression. We further showed that TMYX (25-200 mg/mL) relaxed isolated coronary microvessels. CONCLUSIONS: TMYX attenuates myocardial NR after ischemia and reperfusion by activating the cAMP/PKA and NO/cGMP signaling pathways, further upregulating NO activity and relaxing coronary microvessels.

Mitochondrial quality control in cardiac microvascular ischemia-reperfusion injury: New insights into the mechanisms and therapeutic potentials.

Thrombolytic therapy and revascularization strategies create a complete recanalization of the occluded epicardial coronary artery in patients with myocardial infarction (MI). However, about 35 % of patients still experience an impaired myocardial reperfusion, which is termed a no-reflow phenomenon mainly caused by cardiac microvascular ischemia-reperfusion (I/R) injury. Mitochondria are essential for microvascular endothelial cells' survival, both because of their roles as metabolic energy producers and as regulators of programmed cell death. Mitochondrial structure and function are regulated by a mitochondrial quality control (MQC) system, a series of processes including mitochondrial biogenesis, mitochondrial dynamics/mitophagy, mitochondrial proteostasis, and mitochondria-mediated cell death. Our review discusses the MQC mechanisms and how they are linked to cardiac microvascular I/R injury. Additionally, we will summarize the molecular basis that results in defective MQC mechanisms and present potential therapeutic interventions for improving MQC in cardiac microvascular I/R injury.

Effect of Chinese Medicine on No or Slow Reflow after Percutaneous Coronary Intervention in Myocardial Infarction Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematic review the effect of Chinese medicine (CM) on no or slow reflow after percutaneous coronary intervention (PCI) in myocardial infarction (MI) patients. METHODS: The PubMed, EMBASE databases, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Knowledge Service Platform (Wanfang Database) and Chinese Scientific Journal Database (VIP) were searched up to December 2017. Randomized controlled trials (RCTs) which evaluated the effect of CM therapies on no or slow reflow after PCI in MI patients were included. The primary outcome was the effect of reperfusion. Secondary outcomes were left ventricular ejection fraction, incidence of major adverse cardiovascular events and adverse effect. RESULTS: Ten RCTs covering 814 patients were included. Two studies revealed that the incidence of no or slow reflow was less in Shenmai Injection () group than in the control group measured by thrombolysis in myocardial infarction (TIMI) ⩽ 2 (risk ratio=0.55, 95% confidence interval 0.38 to 0.81, P=0.003, I2=37%). Two studies indicated that Salvianolate Injection showed no additional benefit on no or slow reflow measured by corrected TIMI frame count compared with the conventional treatment (mean difference -4.24, 95% confidence interval -13.03 to 4.54, P=0.34, I2=86%). In addition, Tongxinluo Capsules (), Danhong Injection () and Xuesaitong Injection () may have the potential to reduce no or slow reflow measured during or after PCI in individual studies. CONCLUSIONS: Current evidence from RCTs are not sufficient to evaluate the effect of CM adjuvant therapies on no or slow reflow after PCI for MI patients. The included studies are limited by small sample size and unclear baseline conditions. Further rigorously designed researches and verification studies with sufficient number of patients are warranted.

Effect of Shexiang Tongxin Dropping Pills () on the Immediate Blood Flow of Patients with Coronary Slow Flow.

OBJECTIVE: To observe the immediate effect and safety of Shexiang Tongxin dropping pills (, STDP) on patients with coronary slow flow (CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. METHODS: Coronary angiography (CAG) with corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) was applied (collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary flow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood flow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. RESULTS: There was a significant difference in CTFC between groups (P<0.05). The average CTFC values of the vessels with slow blood flow in CSF patients were, respectively, 49.98 ± 10.01 and 40.42 ± 11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values (frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00 ± 13.32 and 41.80 ± 15.38, 59.00 ± 4.69 and 50.00 ± 9.04, and 51.90 ± 8.40 and 40.09 ± 10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow flow before treatment were significantly decreased after treatment (P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP (all P>0.05). CONCLUSIONS: The immediate effect of STDP in treating CSF patients was apparent. This medication could significantly improve coronary flow without affecting blood pressure or heart rate. Our findings support the potential of Chinese medicine to treat ischemic chest pain.

The Spontaneous Coronary Slow-Flow Phenomenon: Reversal by Intracoronary Nicardipine.

OBJECTIVE: An under-recognized cause of chest pain, the coronary slow-flow (CSF) phenomenon is characterized by delayed coronary opacification during diagnostic angiography in the absence of epicardial coronary artery disease (CAD). Given its angiographic resemblance to no-reflow during percutaneous coronary intervention, a condition associated with microvascular spasm responsive to calcium-channel blockers, we hypothesized that spontaneous CSF may similarly be reversed by intracoronary (IC) nicardipine. METHODS: The effect of IC nicardipine was evaluated in 30 patients. CSF was defined as spontaneously delayed flow (27) in 68/90 vessels (76%). IC nicardipine produced markedly accelerated coronary filling, which was corroborated by TFC analysis. TFC was 47 ± 17 before vs 15 ± 5 after nicardipine (P<.001). All vessels demonstrated TIMI 3 flow and TFC <28 after nicardipine treatment. CONCLUSIONS: IC nicardipine appears highly effective in reversing spontaneous CSF. These findings implicate microvascular spasm in the pathogenesis of CSF. Future studies of oral calcium-channel blockers in the long-term management of CSF are needed.

Coronary No-Reflow Phenomenon in Clinical Practice.

Timely delivered coronary revascularization with no residual anatomical stenosis does not always lead to prompt restoration of anterograde coronary flow and complete myocardial reperfusion. This condition is known as coronary no-reflow and is associated with major clinical adverse events and poor prognosis. The pathophysiology of no-reflow phenomenon is still poorly understood. Proposed mechanisms include distal microembolization of thrombus and plaque debris, ischemic injury, endothelial dysfunction and individual susceptibility to microvascular dysfunction/obstruction. Older age, diabetes, hypercholesterolemia, prolonged ischemic time, hemodynamic instability, high thrombus burden, complex angiographic lesions and multivessel disease are frequently reported to be associated with the no-reflow phenomenon. There is no general consensus on the correct prevention and management of no-reflow. Non-pharmacological measures such as distal embolic protection devices and manual thrombus aspiration did not result in improved flow or reduction of infarct size. Current preventive measures include reduction of time from symptoms onset to reperfusion therapy, and intracoronary administration of vasodilators such as adenosine, verapamil or nitroprusside.

Intracoronary Nicorandil and the Prevention of the No-Reflow Phenomenon During Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND This study aimed to investigate intracoronary nicorandil treatment on the no-reflow phenomenon (NRP) during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and to compare nicorandil with sodium nitroprusside. MATERIAL AND METHODS Patients with sustained acute STEMI who underwent primary PCI (N=120) were randomly assigned to three groups: the nicorandil-treated group (N=40) had 2 mg of nicorandil injected into the coronary artery at 2 mm beyond the occlusion with balloon pre-dilation; the sodium nitroprusside-treated group (N=40) underwent the same procedure, but with 200 µg of sodium nitroprusside; the control group (N=40) received PCI and balloon pre-dilation only. Coronary angiography, incidence of NRP, hypotensive episodes, ST-segment resolution (STR) rate, levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), wall motion score index (WMSI), and left ventricular ejection fraction (LVEF) were measured before and after primary PCI. Major adverse cardiovascular events (MACEs) post-PCI and at three-month follow-up were recorded. RESULTS Patients in the sodium nitroprusside and nicorandil groups had significantly improved thrombolysis in myocardial infarction (TIMI) scores, TIMI myocardial perfusion grade (TMPG), and ST-segment elevation resolution (STR) (P<0.05), and a significantly lower incidence of NRP (P=0.013). The incidence of intraoperative hypotension in the sodium nitroprusside group was significantly greater than the nicorandil and control groups (P=0.035). CONCLUSIONS Patients with sustained acute STEMI undergoing primary PCI, treated with intracoronary nicorandil had a reduced incidence of the NRP, improved myocardial perfusion and cardiac function.

Intracoronary infusion of alprostadil and nitroglycerin with targeted perfusion microcatheter in STEMI patients with coronary slow flow phenomenon.

BACKGROUND: The treating aims of ST-segment elevation myocardial infarction (STEMI) are vessels recanalization and coronary flow restoration. Coronary slow flow phenomenon (CSFP) is one of the common complications in STEMI patients after percutaneous coronary intervention (PCI) and leads to a higher incidence of adverse clinical outcomes. Alprostadil is a kind of liposomal prostaglandin E1 with beneficial effects on vasodilation, platelet disaggregation and fibrinolysis. But it still remains unclear that whether alprostadil can improve the coronary perfusion in STEMI patients with CSFP after PCI. METHODS: In this study, a total of 57 STEMI cases with CSFP were included, 28 of which received 2 µg alprostadil by intracoronary infusion with targeted perfusion microcatheter while the others received 200 µg nitroglycerin. Coronary angiograms were analyzed by two experienced interventional cardiologists who were blinded to the medicine administration. RESULTS: We found that compared with nitroglycerin, alprostadil treatment was significantly more effective in increasing the incidence of TFG 3(78.6% vs. 48.3%, P = 0.021), MBG 3(46.4% vs. 20.7%, P = 0.039), TMPG 3(53.6% vs. 24.1%, P = 0.022) and complete STR (42.8% vs. 17.2%, P = 0.035) and reducing cTFC (28.71 frames vs. 46.03 frames, P = 0.001). Furthermore, in this study, intracoronary infusion of alprostadil with targeted perfusion microcatheter hardly affected the blood pressure and heart rate of patients, and no threaten complication were observed. CONCLUSIONS: Alprostadil can effectively alleviate CSFP, which is at the same time secure even for STEMI patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03296670.

Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis.

BACKGROUND: Despite the restoration of epicardial flow after primary percutaneous coronary intervention (PPCI), myocardial reperfusion remains impaired in a significant proportion of patients. We performed a network meta-analysis to assess the effect of 7 intracoronary agents (adenosine, anisodamine, diltiazem, nicorandil, nitroprusside, urapidil, and verapamil) on the no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) undergoing PPCI. METHODS: Database searches were conducted to identify randomized controlled trials (RCTs) comparing the 7 agents with each other or with standard PPCI. Outcome measures included thrombolysis in myocardial infarction flow grade (TFG), ST-segment resolution (STR), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACEs), and adverse events. RESULTS: Forty-one RCTs involving 4069 patients were analyzed. The addition of anisodamine to standard PPCI for STEMI was associated with improved post-procedural TFG, more occurrences of STR, and improvement of LVEF. The cardioprotective effect of anisodamine conferred a MACE-free survival benefit. Additionally, nitroprusside was regarded as efficient in improving coronary flow and clinical outcomes. Compared with standard care, adenosine, nicorandil, and verapamil improved coronary flow but had no corresponding benefits regarding cardiac function and clinical outcomes. The ranking probability for the 7 treatment drugs showed that anisodamine consistently ranked the highest in efficacy outcomes (TFG < 3, STR, LVEF, and MACEs). No severe adverse events, such as hypotension and malignant arrhythmia, were observed in patients treated with anisodamine. Network meta-regression analysis showed that age, the time to reperfusion, and study follow-up did not affect the treatment effects. CONCLUSIONS: The intracoronary administration of anisodamine appears to improve myocardial reperfusion, cardiac function, and clinical outcomes in patients with STEMI undergoing PPCI. Given the limited quality and quantity of the included studies, more rigorous RCTs are needed to verify the role of this inexpensive and well-tolerated regimen.

Telmisartan ameliorates vascular endothelial dysfunction in coronary slow flow phenomenon (CSFP).

Coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder with an increasing morbidity, and currently, available therapies are of limited clinical value for its cure. Hence, it is urgent to find a novel approach to CSFP treatment. Several studies show that endothelial dysfunction plays a critical role in the aetiology of CSFP. Telmisartan (TMST) is a clinically available anti-hypertensive medicine and has shown its potential properties for improving vascular endothelial function. Thus, we aimed to investigate the effect of TMST on endothelial dysfunction in CSFP, Endothelial-dependent flow-mediated vasodilation, serum levels of nitric oxide, adiponectin, and endothelin-1 were surveyed before and after 3 months of TMST treatment. And the percentages of vasodilator response to acetylcholine (Ach) were detected after 12 weeks of TMST treatment. Compare with pretreatment, flow-mediated vasodilation, nitric oxide, and adiponectin were substantially improved after TMST treatment; meanwhile, endothelin-1 was decreased in the TMST group (all P < .01). Compared with the model group, the vasodilator response to Ach was enormously increased after TMST intervention. Additionally, administration of SU11274 or GW9662 would partially reverse the protective effects of TMST on accumulative concentration-vasodilator responses to Ach (P < .01). We demonstrated that administration of TMST could remarkably increase the mRNA and/or protein levels of hepatocyte growth factor, mesenchymal-epithelial transition factor, peroxisome proliferation-activated receptor γ, whereas dramatically diminish mRNA and/or protein levels of p-JNK1/2, mitogen-activated protein kinase, and nuclear factor kappa B (P < .05). Our results thus implicate that TMST ameliorates endothelial dysfunction in CSFP. It is suggested that TSMF may play an important role in the medication of CSFP.

Effects of dabigatran regulates no­reflow phenomenon in acute myocardial infarction mice through anti­inflammatory and anti­oxidative activities and connective tissue growth factor expression.

Pradaxa is a novel oral anticoagulant, which was originally used to prevent thrombosis following joint replacement surgery. The aim of the current study was to investigate the effect dabigatran on acute myocardial infarction through regulating no­reflow phenomenon and oxidative stress, neutrophil intraplaque infiltration and apoptosis. In the present study, dabigatran significantly inhibited the infarct size, increased arterial pressure and reduced no­reflow phenomenon in acute myocardial infarction (AMI) vehicle rabbits. Treatment with dabigatran significantly inhibited the P65 of nuclear factor κB, tumor necrosis factor α, interleukin (IL)­1ß and IL­6 activities and significantly enhanced the catalase and superoxide dismutase activities in the AMI rabbits. In addition, dabigatran significantly suppressed inducible nitric oxide synthase (iNOS), collagen I, transforming growth factor ß1 (TGF­ß1), α­smooth muscle actin (α­SMA) and connective tissue growth factor (CTGF) protein expression in AMI rabbits. Taken together, these results suggest that the effects of dabigatran inhibit no­reflow phenomenon, infarct size and enhance arterial pressure in AMI through anti­inflammatory and anti­oxidative activity, and regulating iNOS, collagen I, TGF­ß1, α­SMA and CTGF protein expression in AMI rabbits.

Perforated balloon technique: A simple and handy technique to combat no-reflow phenomenon in coronary system.

OBJECTIVE: Examining the efficacy and outcomes of intracoronary (IC) instillation of adenosine using a novel perforated balloon technique (PBT) to combat no-reflow phenomenon during percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). BACKGROUND: Occurrence of no-reflow during PCI is a serious adverse prognostic event and inability to re-establish better flow is associated with poor outcomes. Several pharmacological and non-pharmacological interventions have been used to treat this situation. This series describes the use of PBT for IC adenosine administration and its effects on outcomes during real world interventional practice. METHODS: Subjects comprised of 24 patients with ACS (out of a total of 1,634 patients undergoing PCI between January 2016 and June 2017) in whom we used PBT for IC administration of adenosine to treat coronary no-reflow. RESULTS: PBT for IC adenosine instillation was used in 24 (1.5%) of 1,634 patients undergoing PCI. TIMI grade III flow was established in 21 patients (87.5%). In two patients (8.3%) TIMI grade II flow was established and in one patient (4.2%) we were unsuccessful. CONCLUSION: We demonstrate the safety and efficacy of a novel strategy for adenosine instillation in the distal coronary bed, the PBT. This technique enables rapid and cost-effective treatment of no-reflow phenomenon during PCI for ACS.

Adiponectin improves coronary no-reflow injury by protecting the endothelium in rats with type 2 diabetes mellitus.

To determine the effect of adiponectin (APN) on the coronary no-reflow (NR) injury in rats with Type 2 diabetes mellitus (T2DM), 80 male Sprague-Dawley rats were fed with a high-sugar-high-fat diet to build a T2DM model. Rats received vehicle or APN in the last week and then were subjected to myocardial ischemia reperfusion (MI/R) injury. Endothelium-dependent vasorelaxation of the thoracic aorta was significantly decreased and serum levels of endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were noticably increased in T2DM rats compared with rats without T2DM. Serum APN was positively correlated with the endothelium-dependent vasorelaxation, but negatively correlated with the serum level of ET-1. Treatment with APN improved T2DM-induced endothelium-dependent vasorelaxation, recovered cardiac function, and decreased both NR size and the levels of ET-1, ICAM-1 and VCAM-1. Hypoadiponectinemia was associated with the aggravation of coronary NR in T2DM rats. APN could alleviate coronary NR injury in T2DM rats by protecting the endothelium and improving microcirculation.

Cardioprotective Effects of Nicorandil on Coronary Heart Disease Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND Nicorandil is a nicotinamide ester commonly prescribed for treatment of patients with coronary heart disease (CHD). In the present study, we aimed to explore the cardioprotective effects of nicorandil on CHD patients undergoing elective percutaneous coronary intervention (PCI). MATERIAL AND METHODS One hundred patients with CHD undergoing PCI were randomly divided into a control group (n=48) and a nicorandil group (n=52). Patients in the control group received traditional therapy, and while patients in the nicorandil group received nicorandil before PCI in addition to the traditional therapy. After PCI, all patients underwent coronary angiogram, and TIMI frame count (TFC) was calculated. Plasma levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), myeloperoxidase (MPO), and malondialdehyde (MDA) were determined before and at 6, 18, and 24 h after PCI. Moreover, systolic blood pressure (SBP), mean blood pressure (DBP), heart rate (HR), and left ventricular ejection fractions (LVEF) were recorded before and 3 months after PCI. RESULTS There was a significant difference in the rate of no-reflow (P=0.036) between the 2 groups. The blood frames and levels of cTnI, CK-MB, MPO, and MDA in the nicorandil group were significantly decreased compared to the control group (all P<0.05). Moreover, administration of nicorandil markedly decreased SBP, MBP, and HR, but obviously increased LVEF at 3 months after PCI (P<0.05 or P<0.01). CONCLUSIONS Nicorandil exerts cardioprotective effects on CHD patients undergoing elective PCI by decreasing PCI-related myocardial injury and rate of no-reflow and improvement of LVEF.