Myocardial No-reflow Research Articles

Formononetin alleviates no reflow after myocardial ischemia-reperfusion via modulation of gut microbiota to inhibit inflammation

Gut microflora plays an important role in relieving myocardial no-reflow (NR), formononetin (FMN) has potential effects on NR, however, the relationship between this effect and gut microflora remains unclear. This study aimed to evaluate the role of FMN in alleviating NR effects by regulating gut microflora. We used a myocardial NR rat model to confirm the effect and mechanism of action of FMN in alleviating NR. The rats were randomly divided into sham operation group (Sham), NR group, FMN group and sodium nitroprusside (SNP) group. Thioflavin S staining, Hematoxylin Eosin (HE), myocardial enzyme activity, ultrasonic cardiogram and RT-PCR detection showed that FMN could effectively reduce inflammatory cell infiltration, NR and ischemic area, improve cardiac structure and function and reduce TNF-α and NF-κB gene expression in NR rats. The results of 16S rRNA high-throughput sequencing showed that FMN could increase the abundance of anti-inflammatory bacteria such as Ligilaculum, Coprococcus, Blautia and Muribaculaceae and decrease the abundance of pro-inflammatory bacteria such as Treponema in Spirochaetota and Campylobacterota. The correlation between the differential bacteria in the gut microflora(anti-inflammatory bacteria and pro-inflammatory bacteria) and TNF-α and NF-κB, show that they had a strong correlation. Therefore, the anti-NR mechanism of FMN may be related to increasing the abundance of anti-inflammatory bacteria and reducing the abundance of pro-inflammatory bacteria to inhibit inflammation. This study provides innovative mechanistic insights into the relationship between gut microbiota and myocardial protection, suggesting potential strategy for future treatment of NR.

Tongmai Yangxin pill alleviates myocardial no-reflow by activating GPER to regulate HIF-1α signaling and downstream potassium channels

Context The Tongmai Yangxin pill (TMYX) has potential clinical effects on no-reflow (NR); however, the effective substances and mechanisms remain unclear. Objective This study evaluates the cardioprotective effects and molecular mechanisms of TMYX against NR. Materials and methods We used a myocardial NR rat model to confirm the effect and mechanism of action of TMYX in alleviating NR. Sprague-Dawley (SD) rats were divided into Control (Con), sham, NR, TMYX (4.0 g/kg), and sodium nitroprusside (SNP, 5.0 mg/kg), and received their treatments once a day for one week. In vitro studies in isolated coronary microvasculature of NR rats and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of TMYX and determine the main components, targets, and pathways of TMYX, respectively. Results TMYX (4.0 g/kg) showed therapeutic effects on NR by improving the cardiac structure and function, reducing NR, ischemic areas, and cardiomyocyte injury, and decreasing the expression of cardiac troponin I (cTnI). Moreover, the mechanism of TMYX predicted by network pharmacology is related to the HIF-1, NF-κB, and TNF signaling pathways. In vivo, TMYX decreased the expression of MPO, NF-κB, and TNF-α and increased the expression of GPER, p-ERK, and HIF-1α. In vitro, TMYX enhanced the diastolic function of coronary microvascular cells; however, this effect was inhibited by G-15, H-89, L-NAME, ODQ and four K+ channel inhibitors. Conclusions TMYX exerts its pharmacological effects in the treatment of NR via multiple targets. However, the contribution of each pathway was not detected, and the mechanisms should be further investigated.

A Narrative Review of the Classical and Modern Diagnostic Methods of the No-Reflow Phenomenon.

The incidence of the no-reflow (NR) phenomenon varies depending on the diagnostic criteria used. If just the angiographic criteria are considered (i.e., a degree of thrombolysis in myocardial infarction ≤2), it will be found that the incidence of NR is quite low; on the other hand, when the myocardial NR is taken into account (i.e., a decrease in the quality of myocardial reperfusion expressed by the degree of myocardial blush), the real incidence is higher. Thus, the early establishment of a diagnosis of NR and the administration of specific treatment can lead to its reversibility. Otherwise, regardless of the follow-up period, patients with NR have a poor prognosis. In the present work, we offer a comprehensive perspective on diagnostic tools for NR detection, for improving the global management of patients with arterial microvasculature damage, which is a topic of major interest in the cardiology field, due to its complexity and its link with severe clinical outcomes.

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

Ethnopharmacological relevanceThe 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 studyThis 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 methodsThe 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. ResultsTMYX 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. ConclusionsTMYX 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.

Tongmai Yangxin pill reduces myocardial no-reflow by regulating apoptosis and activating PI3K/Akt/eNOS pathway

Ethnopharmacological relevanceTongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty and was further improved by Professor Ruan Shiyi, a cardiovascular expert at Tianjin University of Traditional Chinese Medicine. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease and can improve vascular endothelial function in patients with angina pectoris or coronary heart disease by up-regulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial no-reflow by up-regulating NO activity and then dilating blood vessels remains unclear. Aim of the studyThis study aimed to reveal whether TMYX can further improve myocardial NR by up-regulating NO activity and then dilating blood vessels. The mechanism underlying PI3K/Akt/eNOS pathway activation and apoptosis regulation is also explored. Materials and methodsThe left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish a NR model. The rats were assigned to 14 groups: control, sham, NR, TMYX (4.0 g/kg), sodium nitroprusside (SNP), Tongxinluo capsule (TXL), PI3K blocker (LY), TMYX + LY, SNP + LY, TXL + LY, eNOS blocker (L-NAME), TMYX + L-NAME, SNP + L-NAME, and TXL + L-NAME groups. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were adopted to evaluate NR and ischemic areas. Cell inflammation degree and edema were assessed by hematoxylin–eosin staining. Automated biochemical analyzer and kit were used to detect the activities of myocardial oxidants, including reactive oxygen species, super oxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins in the PI3K/Akt/eNOS signaling pathway and apoptosis were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was adopted to detect coronary artery diastolic function in vitro. ResultsTMYX reduced NR and ischemic areas; suppressed LV-mass; enhanced EF, FS, LVOT peak, and LVSV; and improved cardiac structure and function. Moreover, it decreased creatine kinase (CK), CK-MB, and lactic dehydrogenase activities. TMYX increased NO and super oxide dismutase activities; inhibited malonaldehyde activity; reduced muscle fiber swelling and inflammatory cell infiltration; and improved vasodilation in vitro. In the NR myocardium, TMYX stimulated myocardial PI3K activities and PI3K (Tyr458) phosphorylation and enhanced Akt activities and Akt phosphorylation at Tyr315. TMYX increased the activities of eNOS and the phosphorylation of eNOS at Ser1177 in the NR myocardium and attenuated cardiomyocyte apoptosis by increasing the expression of Bcl-2 and decreasing that of caspase-3 and Bax. All these effects of TMYX were abolished by the specific inhibitors of PI3K (LY) and eNOS (L-NAME). ConclusionsTMYX attenuates myocardial NR after ischemia and reperfusion by activating the PI3K/Akt/eNOS pathway and regulating apoptosis, further up-regulating NO activity and relaxing coronary microvessels.

China Tongxinluo Study for myocardial protection in patients with Acute Myocardial Infarction (CTS-AMI): Rationale and design of a randomized, double-blind, placebo-controlled, multicenter clinical trial

BackgroundAcute ST-segment elevation myocardial infarction (STEMI) remains a serious life-threatening event. Despite coronary revascularization, patients might still suffer from poor outcomes caused by myocardial no-reflow and ischemic/reperfusion injury. Tongxinluo (TXL), a traditional Chinese medicine, has been preliminarily demonstrated to reduce myocardial no-reflow and ischemic/reperfusion injury. We further hypothesize that TXL treatment is also effective in reducing clinical end points for the patients with STEMI.Methods and resultsThe CTS-AMI trial is a prospective, randomized, double-blind, placebo-controlled, multicenter clinical study in China. An estimated 3,796 eligible patients with STEMI from about 120 centers are randomized 1:1 ratio to TXL or placebo groups. All enrolled patients are orally administrated a loading dose of 8 capsules of TXL or placebo together with dual antiplatelet agents on admission followed by 4 capsules 3 times a day until 12 months. The primary end point is 30-day major adverse cardiovascular and cerebrovascular events, a composite of cardiac death, myocardial reinfarction, emergency coronary revascularization, and stroke. Secondary end points include each component of the primary end point, 1-year major adverse cardiovascular and cerebrovascular events, and other efficacy and safety parameters.ConclusionsResults of CTS-AMI trial will determine the clinical efficacy and safety of traditional Chinese medicine TXL capsule in the treatment of STEMI patients in the reperfusion era.

Intracoronary application of nicorandil regulates the inflammatory response induced by percutaneous coronary intervention.

Intracoronary application of nicorandil can effectively reduce the myocardial no‐reflow (MNR) after percutaneous coronary intervention (PCI). We sought to investigate the mechanisms of nicorandil in preventing MNR, besides that of dilating the coronary microvasculature. A total of 60 patients undergoing PCI were enrolled and randomly divided into a nicorandil group and a control group. Before PCI, 2 mg of nicorandil or an equal volume of normal saline was injected into the coronary artery. Blood samples were collected before, 24 hours and 1 week after PCI and inflammatory cytokines were tested. In the control group, the expression of pro‐inflammatory cytokines was significantly increased, while the anti‐inflammatory cytokines were decreased 24 hours after PCI. In contrast, these changes were reversed in the nicorandil group, indicating that nicorandil regulated the inflammatory response induced by PCI. Then, proteomic analysis was performed to further elucidate the potential mechanisms. A total of 53 differentially expressed proteins (DEPs) were found 24 hours after PCI in the control group, and the changes of these relevant genes were reversed in the nicorandil group. These DEPs were significantly enriched in the inflammatory pathways. In conclusion, the intracoronary application of nicorandil before PCI can regulate the inflammatory responses induced by PCI, which might be an important mechanism of nicorandil in preventing MNR.

Predictors of No-reflow Phenomenon in ST-elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention

Background Primary Percutaneous coronary intervention (PPCI) is an established mainstay in treatment of patients presenting with acute ST elevation myocardial infarction (STEMI). However, successful revascularization of the culprit coronary vessel does not always mean ideal myocardial reperfusion in a portion of patients, mainly because of the no-reflow phenomenon. Myocardial no-reflow is associated with worse contractile dysfunction and higher incidence of complications and is an independent predictor of death and myocardial infarction after PPCI. Objective: To study the relationship between admissions CRP, Albumin, CRP/Albumin ratio, Monocyte, HDL, and Monocyte/HDL ratio, in patients presenting with acute STEMI and angiographic no-reflow after PPCI. Material and Methods: From October 2018 to February 2019, of the 1500 patients who presented with STEMI for PPCI to any of the Ain Shams University Hospitals’ cath labs, we enrolled 150 consecutive patients who had post revascularization angiographic no-reflow. They were allocated to group A. we allocated 150 age, gender, and baseline characteristics matched STEMI patients who had TIMI III flow post revascularization to group B. this was set as the control group. Results: The study population was divided into 2 groups: no-reflow “A” (n = 150) and reflow “B” (n = 150) groups. CRP and Monocytes were significantly higher in the no-reflow group; Albumin and HDL were significantly lower in the no-reflow group. The novel indices, CRP/Albumin ratio (CAR) and Monocytes/HDL ratio (MHR) were both significantly higher in the no-reflow group (p value = 0.000) for both. The tow indices were found to be independent predictors of no-reflow development. Conclusion: Our results suggested that CAR and MHR on admission before PPCI though cheap, and easily measurable laboratory tools, have a significant predictive value with an odds ratio of 0.182 with a p value = 0.000 and 0.321 with a p value = 0.002 respectively. They could help to risk stratify STEMI patients who might suffer from no-reflow phenomenon after PPCI.

Combined use of external therapeutic ultrasound and tirofiban has synergistic therapeutic effects on no-reflow after myocardial reperfusion.

This study aimed to evaluate the effects of the combined use of external therapeutic ultrasound (ETUS) and the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no-reflow in a canine model of acute myocardial infarction after reperfusion. The canine myocardial no-reflow model was established by a 3-hour occlusion of the left anterior desecending coronary artery followed by a 2-hour reperfusion. Twenty-four canines were divided into four groups (6/group): (1) control, (2) tirofiban alone, (3) ETUS combined with tirofiban (ETUS+tirofiban), and (4) ETUS alone. The area of no-reflow in each of the three treatment groups was significantly decreased, compared with the control group, with the ETUS+tirofiban group having the smallest area. Also, the ETUS+tirofiban group had the highest recanalized rate of microvessels in the no-reflow area and fewer impaired cellular organelles. The recovery rates of the endocardial and middle circumferential strain as well as longitudinal strain in the ETUS+tirofiban group were significantly greater than those of the tirofiban group. Moreover, the expression of hypoxia-inducible factor-1α (HIF-1α) was significantly increased in the ETUS+tirofiban group, compared with the other groups. The combined use of ETUS and tirofiban offers synergistic benefits for the treatment of myocardial no-reflow.

Increased Platelet-leukocyte Aggregates Are Associated With Myocardial No-reflow in Patients With ST Elevation Myocardial Infarction

ObjectiveWe aimed to investigate the association between platelet-leukocyte aggregates (PLA) levels on admission and the risk of myocardial no-reflow in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). MethodsA total of 83 patients with STEMI undergoing primary PCI were included in the current study. Platelet-leukocyte conjugates (PLA), including platelet-monocyte aggregates (PMA), platelet-neutrophil aggregates (PNA) and platelet-lymphocyte aggregates were studied by flow cytometry in peripheral venous blood. No-reflow was defined as coronary blood flow grade thrombolysis in myocardial infarction ≤2 or thrombolysis in myocardial infarction 3 and myocardial blush grade ≤2. ResultsNo-reflow was observed in 19 patients (22.9%). Compared with the reflow group, the level of PNA (76.5 ± 13.3) and PMA (90.3 ± 5.2) before PCI no-reflow group was significantly higher than that in normal reflow (P < 0.001). Using multiple logistic regression analysis, PNA (odds ratio [OR] = 1.179; 95% CI: 1.035-1.342; P = 0.013) and PMA (OR = 1.248; 95% CI: 1.040-1.498; P = 0.017) were found to be a significant predictor of no-reflow together with pain to balloon time (OR = 1.022; 95% CI: 1.002-1.041; P = 0.028), estimated glomerular filtration rate (OR = 1.311; 95% CI: 1.009-1.856; P = 0.047) and higher thrombus burden (OR = 0.061; 95% CI: 0.006-0.658; P = 0.021). Receiver operating characteristic curve analysis revealed that PNA (area under the curve = 0.881; 95% CI: 0.809-0.952; P < 0.001), PMA (area under the curve = 0.794; 95% CI: 0.699-0.889; P < 0.001) have important predictive value for the myocardial no-reflow. ConclusionsOur study indicated that preprocedural increased PLA levels display a significantly independent association with no-reflow phenomenon after PCI. Increased PLA levels may predict the development of no-reflow phenomenon in patients with STEMI who underwent PCI.

Matrix Metalloproteinase-9 in the Culprit Coronary Artery and Myocardial No-Reflow

Matrix Metalloproteinases (MMPs) have been implicated in the pathogenesis of acute myocardial infarction (AMI). However, little is known about the association between MMP-9 and myocardial no-reflow. The aim of this study was to evaluate the role of MMP-9 in the culprit coronary artery as a predictor of no-reflow in patients with ST-elevation AMI. Ninety patients with ST-elevation AMI who underwent emergency percutaneous coronary intervention were consecutively recruited in this study. Blood samples were obtained from the extraction catheter placed distal to the culprit lesion at the beginning of percutaneous coronary intervention. No-reflow was defined as a coronary thrombolysis in myocardial infarction flow grade ≤2 after vessel reopening or thrombolysis in myocardial infarction flow 3 with a final myocardial blush grade ≤2. No-reflow was observed in 25 patients (27.8%). Using multiple logistic regression analysis, local MMP-9 levels (odds ratio [OR] = 3.356; confidence interval [CI]: 1.441-5.881; P = 0.007) were found to be a significant risk factor of no-reflow together with lesion length (OR = 6.985; CI: 2.574-11.533; P = 0.009) and time to balloon (OR = 2.143; CI: 1.216-5.901; P = 0.042). Elevation of MMP-9 level in the culprit coronary artery may predict no-reflow in patients with ST-elevation AMI.

Reply to “Letter to the editor: Intravital imaging of the association between intravascular neutrophil extracellular traps and microvascular obstruction using multiphoton microscopy”

reply: We thank Dr. Tanaka and colleagues ([11][1]) for their comments on our article published in the American Journal of Physiology-Heart and Circulatory Physiology , entitled “Neutrophil extracellular traps in ischemia/reperfusion injury-induced myocardial no-reflow: therapeutic potential of

Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy.

Emerging evidence suggests a potential role of neutrophil extracellular traps (NETs) in linking sterile inflammation and thrombosis. We hypothesized that NETs would be induced during myocardial ischemia-reperfusion (I/R), and NET-mediated microthrombosis may contribute to myocardial "no-reflow". Male Wistar rats were randomly divided into I/R control, DNase (DNase I, 20 μg/rat), recombinant tissue-type plasminogen activator (rt-PA, 420 μg/rat), DNase + rt-PA, and sham control groups after 45-min myocardial ischemia. In situ NET formation, the anatomic "no re-flow" area, and infarct size were evaluated immediately after 3 h of reperfusion. Long-term left ventricular (LV) functional and histological analyses were performed 45 days after operation. Compared with the I/R controls, the DNase + rt-PA group exhibited reduced NET density [8.38 ± 1.98 vs. 26.86 ± 3.07 (per 200 × field), P < 0.001] and "no-flow" area (15.22 ± 0.06 vs. 34.6 ± 0.05%, P < 0.05) in the ischemic region, as well as reduced infarct size (38.39 ± 0.05 vs. 71.00 ± 0.03%, P < 0.001). Additionally, compared with the I/R controls, DNase + rt-PA treatment significantly ameliorated I/R injury-induced LV remodeling (LV ejection fraction: 64.22 ± 3.37 vs. 33.81 ± 2.98%, P < 0.05; LV maximal slope of the LV systolic pressure increment: 3,785 ± 216 vs. 2,596 ± 299 mmHg/s, P < 0.05). The beneficial effect was not observed in rats treated with DNase I or rt-PA alone. Our study provides evidence for the existence of NETs in I/R-challenged myocardium and confirms the long-term benefit of a novel DNase-based reperfusion strategy (DNase I + rt-PA), which might be a promising option for the treatment of myocardial I/R injury and coronary no-reflow.

ASSA14-01-03 Elevation of Matrix Metalloproteinase-9 in the Culprit Coronary Artery Predicts Myocardial No-re flow

Background Matrix metalloproteases (MMPs) have been implicated in the pathogenesis of acute myocardial infarction (AMI). However, little is known about the association between MMP-9 and myocardial no-reflow. The aim of this study was to evaluate the role of MMP-9 at the infarct-related artery as a predictor of no-reflow in patients with ST-elevation AMI. Methods We prospectively enrolled 90 eligible ST-elevation AMI patients, undergoing successful primary PCI. Blood samples were obtained from the extraction catheter placed distal to the culprit lesion at the beginning of PCI. The levels of MMP-9 were determined in duplicate using the RayBio enzyme-linked immunosorbent assay. Results No-reflow was observed in twenty-five patients (27.8%). Using multiple logistic regression analysis, local MMP-9 level (OR 3.356, CI: 1.441–16,881; p = 0.007) were found to be a significant risk factor of no-reflow together with lesion length (OR 6.985, CI: 1.574–18.533; p = 0.009) and thrombus score (OR 5.105, CI: 1.825–25.138; p = 0.041). Conclusions Elevation of MMP-9 level in the culprit coronary artery may predict no-reflow in patients with ST-elevation AMI underwent PCI.

Prospective study of effects of endogenous estrogens on myocardial no-reflow risk in postmenopausal women with acute myocardial infarction.

The relationship between endogenous estrogens and cardiovascular disease in menopausal women remains poorly understood. Studies examining the relationship have yielded conflicting results. Therefore, we performed this study to prospectively assess the effects of endogenous estrogen on the risk of myocardial no-reflow in postmenopausal women with ST-elevation myocardial infarction (STEMI). Consecutive 100 postmenopausal women diagnosed with STEMI and who had undergone emergence percutaneous coronary intervention (PCI) were included in this study. Blood samples were obtained before PCI and assayed for endogenous sex hormones. Logistic regression models were developed with adjustment for confounders. Compared with normal-reflow group, the circulating levels of estrone, estradiol, sex hormone binding globulin (SHBG), and hypersensitive C-reaction protein (Hs-CRP) were significantly higher in the no-reflow group (P < 0.05). In univariable logistic regression models, lesion length, reference luminal diameter, thrombus score ≥ 4, and the levels of estrone, estradiol, and SHBG were all found to be positively associated with the risk of no-reflow (P < 0.05). After adjusting for these factors, thrombus score ≥ 4 (OR = 4.994, CI 1.987-10.518; P = 0.035), SHBG (OR = 0.800, CI 0.341-0.983; P = 0.047), and estradiol levels (OR 4.091, CI 1.105-8.582; P = 0.046) continued to demonstrate strong positive associations with the risk of no-reflow. Our data showed that high circulating levels of endogenous estrogens have a positive and statistically significant relationship with no-reflow in postmenopausal women with STEMI. It has been suggested that estrogens may have a potential detrimental effect on myocardial no-reflow. However, our results need to be confirmed in a larger population.

Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in rabbits. No-reflow was not dependent on the reduction of infarct size.

Link between aortic valve sclerosis and myocardial no-reflow in ST-segment elevation myocardial infarction

The"no-reflow" phenomenon is associated with a worse prognosis at follow-up for patients with acute ST-segment elevation myocardial infarction (STEMI). Predicting and preventing no-reflow is therefore a crucial step in improving the prognosis of STEMI patients. The purpose of this study was to investigate the association between aortic valve sclerosis (AVS) and myocardial no-reflow in patients with STEMI. Patients with a first-time diagnosis of STEMI were enrolled consecutively. No-reflow was defined as a final TIMI 3 flow with a myocardial blush of grade < 2, temporary epicardial coronary no-reflow, and distal coronary occlusion. AVS was defined by echocardiography as thickening and calcification of the normal trileaflet aortic valve without obstruction to the left ventricular outflow. No-reflow developed in 41 patients. In univariate analysis, age, male gender, smoking, culprit lesion Syntax score (SX score), and hypertension were significantly associated with no-reflow. Multivariate binary logistic regression analyses demonstrated age [95 % confidence interval (CI), 1.024-1.096; p=0.001), AVS (95 % CI, 1.002-1.100; p=0.039], culprit lesion SX score (95 % CI, 1.08-1.021 p=0.008), and symptom-to-balloon time (95 % CI, 1.020-1.097; p=0.002) as independent determinants of myocardial no-reflow. AVS was significantly and independently associated with myocardial no-reflow in STEMI patients.

GW24-e2490 Effects of Valsartan on No-Reflow after Myocardial Ischemia Reperfusion in Rats

Objectivesto evaluate the effects of valsartan on myocardial no-reflow and its probable mechanism in signal transduction pathway.MethodsFifty-six male SD rats were randomly assigned to four groups: shame group, ischaemia and...

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.

Protein kinase A-mediated cardioprotection of Tongxinluo relates to the inhibition of myocardial inflammation, apoptosis, and edema in reperfused swine hearts

Background Our previous studies have demonstrated that Tongxinluo (TXL), a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A (PKA)-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. Methods In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL (0.05 g/kg, gavaged one hour prior to ischemia), and TXL + H-89 (a PKA inhibitor, intravenously and continuously infused at 1.0 μg/kg per minute) groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein (p-CREB) (Ser133), tumor necrosis factor α (TNF-α), P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. Results TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% (P&lt;0.05). TXL pretreatment increased the PKA activity and the expression of Ser133 p-CREB in the reflow and no-reflow myocardium (P &lt;0.05). TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-α and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. Conclusion PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.