Reperfusion In Myocardial Infarction Research Articles

Assessment of microvascular occlusion in re-perfused myocardial infarction patients using cardiac magnetic resonance

Abstract Background and objective Primary percutaneous coronary intervention (PPCI) is the gold standard for myocardial reperfusion in ST-segment elevation myocardial infarction (STEMI). Numerous studies have shown that thrombus aspiration can prevent distal embolization, reducing the risk of microvascular obstruction (MVO). Cardiac magnetic resonance (CMR) is considered the gold standard for evaluation of MVO. The aim of this study is to evaluate the efficacy of thrombus aspiration as adjunctive technique to primary PCI, in reducing incidence and extent of MVO in STEMI patients evaluated by CMR. Methods Ninety-three patients with heavy thrombus burden were enrolled in this study, sixty-five met our inclusion criteria. Aspiration thrombectomy followed by PCI was done for thirty-one patients (aspiration group) and conventional PCI, without aspiration thrombectomy, was done for thirty-four patients (conventional group). Primary end points were occurrence and extent of microvascular obstruction (MVO) evaluated by cardiac magnetic resonance (CMR). Results The incidence of microvascular obstruction (MVO) was significantly higher in conventional group (18 patients, 52.9%) when compared with aspiration group (7 patients, 22.6%) (p-value = 0.012). Moreover, significant difference existed between studied groups as regard MVO extent. In aspiration group, MVO extended to > 4 segments in 3 patients (9.7%) while in conventional group, MVO extended to > 4 segments in 13 patients (38.2%) (p-value = 0.012). Conclusion Aspiration thrombectomy as adjunctive technique to PCI in STEMI population maintains the integrity of coronary microvasculature and reduces both incidence and extent of MVO.

Timeliness of reperfusion in ST-segment elevation myocardial infarction and outcomes in Kerala, India: results of the TRUST outcomes registry.

Transatlantic guidelines endorse quality metrics for timely reperfusion in patients with ST-elevation myocardial infarction (STEMI). Compliance in low- and middle-income countries (LMICs) is largely unknown. We prospectively evaluated 2928 STEMI patients in Kerala, India, across 16 PCI-capable hospitals who received reperfusion with either primary percutaneous coronary intervention (PPCI) or fibrinolysis. Primary endpoint was a major adverse cardiovascular event (MACE) composite of death, non-fatal myocardial infarction, stroke or readmission for heart failure at 1-year. Among reperfused STEMI patients, 320 (10.9%) received timely reperfusion with either PPCI or fibrinolysis, 1985 (67.8%) received delayed PPCI, and 623 (21.3%) received delayed fibrinolysis. Timely reperfusion had lower unadjusted MACE rates than delayed PCI or fibrinolysis (timely reperfusion: 11.9%, delayed PPCI: 13.6%, delayed fibrinolysis: 23.9%, P < 0.001). Mortality was lowest in the timely reperfusion group (timely reperfusion: 6.3%, delayed PPCI: 7.8%, delayed fibrinolysis 18.8%, P < 0.001). After multivariate analysis, delayed fibrinolysis had a higher MACE rate (HR 1.52 95% CI 1.04-2.21) and mortality (HR 1.97, 95% CI 1.18-3.25) compared to timely reperfusion. Total ischemic time > 3h and delayed first medical contact-to-needle time predicted MACE at 1 year. Among STEMI patients in Kerala, India, only one in 10 eligible patients received timely reperfusion. Longer total ischemic times and delayed fibrinolysis were associated with 1-year MACE. Improving timely reperfusion is critical to enhancing STEMI outcomes in LMICs. What is already known on this topic Given the established link between delay to reperfusion and worse major adverse cardiac events (MACE), global efforts have concentrated on minimizing different components of the total ischemic time to improve ST-elevation myocardial infarction (STEMI) outcomes. Compliance in low- and middle-income countries (LMICs) is largely unknown. What this study adds In this cohort of STEMI patients in Kerala, India, total ischemic time and first medical contact-to-needle time correlated with long-term MACE rates, whereas other timeliness indicators did not. How this study might affect research, practice or policy Our study highlights the significant barriers to accessing STEMI care that are prevalent in LMICs despite incremental growth in the number of PCI-capable hospitals. The pre-hospital phase within total ischemic time is the most important quality improvement metric of STEMI care in LMICs, especially for patients chosen for fibrinolysis.

Association between admission blood pressure and spontaneous reperfusion and long-term prognosis in STEMI patients: an observational and multicenter study

BackgroundThis study aims to assess the associations of admission systolic blood pressure (SBP) level with spontaneous reperfusion (SR) and long-term prognosis in ST-elevation myocardial infarction (STEMI) patients.MethodsData from 3809 STEMI patients who underwent primary percutaneous coronary intervention within 24 h, as recorded in the Chinese STEMI PPCI Registry (NCT04996901), were analyzed. The primary endpoint was SR, defined as thrombolysis in myocardial infarction grade 2–3 flow of IRA according to emergency angiography. The second endpoint was 2-year all-cause mortality. The association between admission BP and outcomes was evaluated using Logistic regression or Cox proportional hazards models with restricted cubic splines, adjusting for clinical characteristics.ResultsAdmission SBP rather than diastolic BP was associated with SR after adjustment. Notably, this relationship exhibits a nonlinear pattern. Below 120mmHg, There existed a significant positive correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg: 0.800; 95% CI: 0.706–0.907; p<0.001); whereas above 120mmHg, no further improvement in SR was observed (adjusted OR per 10-mmHg increase for SBP >120 mm Hg: 1.019; 95% CI: 0.958–1.084, p = 0.552). In the analysis of the endpoint event of mortality, patients admitted with SBP ranging from 121 to 150 mmHg exhibited the lowest mortality compared with those SBP ≤ 120mmHg (adjusted HR: 0.653; 95% CI: 0.495–0.862; p = 0.003). In addition, subgroups analysis with Killip class I-II showed SBP ≤ 120mmHg was still associated with increased risk of mortality.ConclusionThe present study revealed admission SBP above 120 mmHg was associated with higher SR,30-d and 2-y survival rate in STEMI patients. The admission SBP could be a marker to provide clinical assessment and treatment.Trial registrationClinicalTrials.gov (NCT04996901), 07/27/2021.

MicroPET Imaging of Riboflavin Transporter 3 Expression in Myocardial Infarction/Reperfusion Rat Models with Radiofluorinated Riboflavin.

Riboflavin transporter 3 (RFVT3) represents a potential cardioprotective biotarget in energetic metabolism reprogramming after myocardial infarction/reperfusion (MI/R). This study investigated the feasibility of noninvasive real-time quantification of RFVT3 expression after MI/R with an radiolabeled probe 18F-RFTA in a preclinical rat model of MI/R. The tracer 18F-RFTA was radio-synthesized manually and characterized on the subjects of radiolabeling yield, radiochemical purity, and stability in vivo. MI/R and sham-operated rat models were confirmed by cardiac magnetic resonance imaging (cMRI) and single-photon-emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m sestamibi (99mTc-MIBI). Positron emission tomography (PET) imaging of MI/R and sham-operated rat models were conducted with 18F-RFTA. Ex vivo autoradiography and RFVT3 immunohistochemical (IHC) staining were conducted to verify the RFVT3 expression in infarcted and normal myocardium. 18F-RFTA injection was prepared with high radiochemical purity (>95%) and kept stable in vitro and in vivo. 18F-RFTA PET revealed significant uptake in the infarcted myocardium at 8 h after reperfusion, as confirmed by lower 99mTc-MIBI perfusion and decreased intensity of cMRI. Conversely, there were only the tiniest uptakes in the normal myocardium and blocked infarcted myocardium, which was further corroborated by ex vivo autoradiography. The RFVT3 expression was further confirmed by IHC staining in the infarcted and normal myocardium. We first demonstrate the feasibility of imaging RFVT3 in infarcted myocardium. 18F-RFTA is an encouraging PET probe for imaging cardioprotective biotarget RFVT3 in mitochondrial energetic metabolism reprogramming after myocardial infarction. Noninvasive imaging of cardioprotective biotarget RFVT3 has potential value in the diagnosis and therapy of patients with MI.

Position statement for improvement in reperfusion of ST-elevation myocardial infarction in Latin America

Position statement for improvement in reperfusion of ST-elevation myocardial infarction in Latin America

Novel Fibrillar and Non-Fibrillar Collagens Involved in Fibrotic Scar Formation after Myocardial Infarction.

Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.

Galanin Coordinates Macrophage-Associated Fibro-Inflammatory Response and Mitochondrial Integrity in Myocardial Infarction Reperfusion Injury.

Myocardial infarction activates an intense fibro-inflammatory reaction that is essential for cardiac remodeling and heart failure (HF). Bioactive peptide galanin plays a critical role in regulating cardiovascular homeostasis; however, its specific functional relevance in post-infarction fibro-inflammatory reprogramming remains obscure. Here, we show that galanin coordinates the fibro-inflammatory trajectory and mitochondrial integrity in post-infarction reperfusion injury. Aberrant deposition of collagen was associated with a marked increase in CD68-positive macrophage infiltration in cardiac tissue in mice subjected to myocardial ischemia/reperfusion (I/R) for 14 days compared to sham controls. Furthermore, we found that the myocardial expression level of a specific marker of M2 macrophages, CD206, was significantly down-regulated in I/R-challenged mice. In contrast, galanin treatment started during the reperfusion phase blunted the fibro-inflammatory responses and promoted the expression of CD206 in I/R-remodeled hearts. In addition, we found that the anti-apoptotic and anti-hypertrophic effects of galanin were associated with the preservation of mitochondrial integrity and promotion of mitochondrial biogenesis. These findings depict galanin as a key arbitrator of fibro-inflammatory responses to cardiac I/R injury and offer a promising therapeutic trajectory for the treatment of post-infarct cardiovascular complications.

Illusion of revascularization: does anyone achieve optimal revascularization during percutaneous coronary intervention?

This Perspective article is a form of 'pastiche', inspired by the 1993 review by Lincoff and Topol entitled 'Illusion of reperfusion', and explores how their concept continues to apply to percutaneous revascularization in patients with coronary artery disease and ischaemia. Just as Lincoff and Topol argued that reperfusion of acute myocardial infarction was facing unresolved obstacles that hampered clinical success in 1993, we propose that challenging issues are similarly jeopardizing the potential benefits of stent-based angioplasty today. By analysing the appropriateness and efficacy of percutaneous coronary intervention (PCI), we emphasize the limitations of relying solely on visual angiographic guidance, which frequently leads to inappropriate stenting and overtreatment in up to one-third of patients and the associated increased risk of periprocedural myocardial infarction. The lack of optimal revascularization observed in half of patients undergoing PCI confers risks such as suboptimal physiology after PCI, residual angina and long-term stent-related events, leaving an estimated 76% of patients with an 'illusion of revascularization'. These outcomes highlight the need to refine our diagnostic tools by integrating physiological assessments with targeted intracoronary imaging and emerging strategies, such as co-registration systems and angiography-based computational methods enhanced by artificial intelligence, to achieve optimal revascularization outcomes.

Position statement for improvement in reperfusion of ST-elevation myocardial infarction in Latin America

The treatment of ST-segment elevation myocardial infarction has barriers depending on the geographic region. Primary coronary angioplasty is the treatment of choice, if it is performed on time and by experienced operators. However, when it is not available, the administration of fibrinolysis and referral for rescue angioplasty, in case of negative reperfusion, is the best strategy. In the same way, coronary angioplasty, as part of a pharmacoinvasive strategy, is the best alternative when there is positive reperfusion. The development of infarct treatment networks increases the number of patients reperfused within the recommended times and improves outcomes. In Latin America, national myocardial infarction treatment programs should focus on improving outcomes, and long-term success depends on working toward defined goals and enhancing functionality, therefore programs should develop capacity to measure their performance. The following document discusses all of these alternatives and suggests opportunities for improvement.

Intracoronary microcatheter indwelling for continuous pumping of low-dose thrombolytic drugs: A new approach to reperfusion in acute myocardial infarction.

Reperfusion therapy of acute myocardial infarction (AMI) refers to physical or chemical recanalization and restoration of blood flow to an occluded coronary artery, and current techniques for reperfusion therapy include intravenous thrombolysis, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The number of patients receiving emergency CABG in the real world is decreasing due to the disadvantages of CABG and the improvement in PCI procedures. Thrombolytic therapy has some disadvantages such as low recanalization rate, high risk of reocclusion and bleeding, and short time window. On the other hand, intracoronary interventional therapy may meet the requirements of "early, complete and persistent" patency of coronary arteries at different time points. However, in the emergency PCI, although thrombus aspiration via a catheter or balloon dilation is performed, residual thrombus with heavy or low TIMI (thrombolysis in myocardial infarction) myocardial perfusion grading is still observed in some patients, suggesting disordered microcirculation. Currently, the treatment of microcirculatory disturbance in emergency PCI mainly employed injection of tirofiban, adenosine, thrombolytic agent or other drugs into the local area via a microcatheter in a short time, all of which can significantly reduce the thrombus load and improve TIMI perfusion. Herein, we report that a microcatheter was indwelled in the coronary artery for continuous pumping of low-dose thrombolytic drugs as reperfusion therapy in 12 patients with acute and subacute MI.

Determinants and Prognoses of Visual-Functional Mismatches After Mechanical Reperfusion in ST-Elevation Myocardial Infarction.

Discordance between the anatomy and physiology of the coronary has important implications for managing patients with stable coronary disease, but its significance in ST-elevation myocardial infarction has not been fully elucidated. The retrospective study involved patients diagnosed with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI), along with quantitative coronary angiography (QCA) and quantitative flow ratio (QFR) assessments. Patients were stratified into four groups regarding the severity of the culprit vessel, both visually and functionally: concordantly negative (QCA-diameter stenosis [DS] ≤ 50% and QFR > 0.80), mismatch (QCA-DS > 50% and QFR > 0.80), reverse mismatch (QCA-DS ≤ 50% and QFR ≤ 0.80), and concordantly positive (QCA-DS > 50% and QFR ≤ 0.80). Multivariable logistic regression analyses were conducted to identify the clinical factors linked to visual-functional mismatches. Kaplan‒Meier analysis was conducted to estimate the 18-month adverse cardiovascular events (MACE)-free survival between the four groups. The study involved 310 patients, with 68 presenting visual-functional mismatch, and 51 exhibiting reverse mismatch. The mismatch was associated with higher angiography-derived microcirculatory resistance (AMR) (adjusted odds ratio [aOR]=1.016, 95% CI: 1.010-1.022, P<0.001). Reverse mismatch was associated with larger area stenosis (aOR=1.044, 95% CI: 1.004-1.086, P=0.032), lower coronary flow velocity (aOR=0.690, 95% CI: 0.567-0.970, P<0.001) and lower AMR (aOR=0.947, 95% CI: 0.924-0.970, P<0.001). Additionally, the mismatch group showed the worst 18-month MACE-free survival among the four groups (Log rank test p = 0.013). AMR plays a significant role in the occurrence of visual-functional mismatches between QCA-DS and QFR, and the mismatch group showed the worst prognosis.

Predictors of myocardial functional recovery after successful reperfusion of acute St elevation myocardial infarction using speckle tracking echocardiography

Predictors of myocardial functional recovery after successful reperfusion of acute St elevation myocardial infarction using speckle tracking echocardiography

Principle and design of clinical efficacy observation of extracorporeal cardiac shock wave therapy for patients with myocardial ischemia-reperfusion injury: A prospective randomized controlled trial protocol

Background Acute ST-segment elevation myocardial infarction (STEMI) remains a serious life threatening event with a poor prognosis due to myocardial ischemia/reperfusion injury despite coronary revascularization. Extracorporeal cardiac shock wave (ECSW) is a safe, effective and non-invasive new method for the treatment of cardiovascular diseases. The current results show that extracorporeal cardiac shock wave provides a new treatment option for patients with severe and advanced coronary heart disease. However, there are relatively few clinical studies on the application of in vitro cardiac shock waves in patients with myocardial ischemia-reperfusion injury. We hypothesized that extracorporeal cardiac shock therapy would also be effective in reducing clinical endpoints in patients with STEMI reperfusion. Objective This study is order to provide a new therapeutic method for patients with myocardial ischemia-reperfusion injury and reveal the possible mechanism of ECSW for ischemia-reperfusion injury. Methods and materials CEECSWIIRI is a single-center, prospective randomized controlled trial that plans to enroll 102 eligible patients with acute ST-segment elevation myocardial infarction reperfusion. Eligible patients with STEMI reperfusion will be randomly divided into external cardiac shock therapy (ECSW) trial group and blank control group. The blank control group will receive optimal drug therapy, and the experimental group will receive optimal drug therapy combined with ECSW. The shock wave treatment plan will be 3-month therapy, specifically 1 week of treatment per month, 3 weeks of rest, 3 times of ECSW in each treatment week, respectively on the first day, the third day and the fifth day of the treatment week, lasting for 3 months and follow-up for 2 years. The primary endpoint will be to assess the 2-year improvement in all-cause death, re-hospitalization due to cardiovascular disease, major unintentional cerebrovascular events, including cardiogenic death, myocardial infarction, heart failure, arrhythmia, emergency coronary revascularization, and stroke in patients with STEMI reperfusion. Secondary endpoints will include improvements in angina pectoris, quality of life, cardiac structure and function, coronary microcirculation, and endothelial progenitor cell-derived miR-140-3p in relation to survival outcomes. Trial registration number ClinicalTrial.gov.org PRS:NCT05624203; Date of registration: November 12, 2022.

Reperfusion Arrhythmia in Acute Myocardial Infarction

Management of reperfusion in acute myocardial infarction is an important component of myocardial cell survival to minimize the area experiencing infarction and improve patient clinical outcomes. However, this reperfusion also contributes to myocardial injury which is preceded by the ischemic process. One of the injuries related to the ischemia-reperfusion process in the myocardium is reperfusion arrhythmia. Reperfusion arrhythmias from several studies can begin to occur in the first minutes after restoration of obstructed coronary flow. The features of reperfusion arrhythmia can include accelerated idioventricular rhythm, ventricular tachycardia, ventricular fibrillation, and other arrhythmias. The mechanism of reperfusion arrhythmia can be excess calcium in the cells, oxidative stress due to an increase reactive oxygen species, energy metabolism disorders, and neutrophil accumulation. Excessive intracellular calcium and other mechanisms cause a delay in the depolarization of previously ischemic cells. This reperfusion arrhythmia requires special attention because it can disrupt hemodynamics and patient outcomes after reperfusion procedures. Knowledge of the mechanisms of reperfusion arrhythmias will guide clinicians to provide better management during and after reperfusion procedures.

Non-contrast cine cardiovascular magnetic resonance-based radiomics nomogram for predicting microvascular obstruction after reperfusion in ST-segment elevation myocardial infarction.

This study aimed to develop and validate a cine cardiovascular magnetic resonance (CMR)-based radiomics nomogram model for predicting microvascular obstruction (MVO) following reperfusion in patients with ST-segment elevation myocardial infarction (STEMI). In total, 167 consecutive STEMI patients were retrospectively enrolled. The patients were randomly divided into training and validation cohorts with a ratio of 7:3. All patients were diagnosed with myocardial infarction with or without MVO based on late gadolinium enhancement imaging. Radiomics features were extracted from the cine CMR end-diastolic volume phase of the entire left ventricular myocardium (3D volume). The least absolute shrinkage and selection operator (LASSO) regression was employed to select the features that were most relevant to the MVO; these features were then used to calculate the radiomics score (Rad-score). A combined model was developed based on independent risk factors screened using multivariate regression analysis and visualized using a nomogram. Performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). The univariate analysis of clinical features demonstrated that only cardiac troponin I (cTNI) was significantly associated with MVO. LASSO regression revealed that 12 radiomics features were strongly associated with MVO. Multivariate regression analysis indicated that cTNI and Rad-score were independent risk factors for MVO. The nomogram based on these two features achieved an area under the curve of 0.86 and 0.78 in the training and validation cohorts, respectively. Calibration curves and DCA indicated the clinical feasibility and utility of the nomogram. A CMR-based radiomics nomogram offers an effective means of predicting MVO without contrast agents and radiation, which could facilitate risk stratification of patients with STEMI after PCI for reperfusion.

Prognostic role of left atrial morpho-functional parameters in left ventricular remodeling following acute st-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Despite prompt reperfusion and optimal medical therapy of acute ST-elevation myocardial infarction (STEMI), patients may undergo left ventricular (LV) remodeling (REM), which may lead to systolic and/or diastolic heart failure. Little is known regarding factors and mechanisms leading to LV REM, and this knowledge gap hinders potential strategies to prevent this complication. Left atrium (LA) functional and dimensional parameters are emerging as independent prognostic markers in ischemic heart disease. Purpose The present study aims at exploring the potential role of LA morpho-functional parameters by CMR-FT in predicting LV REM following STEMI. Methods This study derives from a sub-analysis of the prospective and multicenter "VavirimS" trial. All patients were assessed through 2 consecutive CMR scans, at 1 and 6 months after STEMI. CMR-FT was applied to both LA and LV. The endpoint was to evaluate the association between LA volumes and phasic functions with LV REM at 6-month follow up, defined as: i) LV REMEDV: ≥10% increase in LV end diastolic volume (EDV); ii) LV REMEDV-ESV: ≥12% increase in LV EDV and ≥6% LV end systolic volume (ESV). Results Out of 193 patients included in the VavirimS trial, 149 were enrolled and 44 have been excluded either for inadequate image quality for CMR-FT analysis or for the presence of factors impacting on LA morphology and function (i.e. mitral regurgitation and atrial fibrillation). LV REMEDV occurred in 34 patients (23%), who showed worse LA strain parameters (reservoir, conduit and booster function), LV global radial strain (GRS) and LV global circumferential epicardial strain [Fig. 1]. At multivariate analysis, LA reservoir and LV global radial strain (GRS) were confirmed as independent predictors of LV-REMEDV [Fig. 1]. The best cut-off for LA reservoir and LV GRS were 20% (sensitivity 97%; specificity 45%) and 56% (sensitivity 67%; specificity 69%), respectively. LV REMEDV-ESV occurred in 17 patients (11%), who showed reduced LA strain and LV GRS [Fig. 1]. The only independent predictor of LV remodeling in this group was LA reservoir [Fig. 1]. A subgroup analysis has been performed on two groups, according to EF: i) p-EF: preserved ejection fraction, ii) r-EF: reduced ejection fraction. In the p-EF group both LA reservoir and LV GRS were confirmed to be associated with LV REM [Fig. 1], while in the r-EF group the only independent predictor of LV REM was LV GRS [Fig. 1]. Conclusions CMR-derived LA reservoir and LV GRS are independent predictors of LV remodeling following STEMI. In patients with preserved EF LA reservoir is confirmed as independent predictor of LV remodeling, hinting at early and subclinical impairment of left chambers compliance. LA functional parameters following STEMI may help physicians in identifying patients at higher risk of LV remodeling.

Upregulation of P2Y14 receptor in neutrophils promotes inflammation after myocardial ischemia/reperfusion injury

BackgroundP2Y14 receptor is expressed in neutrophils and is involved in activation of inflammatory signaling. However, the expression and function of P2Y14 receptor in neutrophils after myocardial infarction/reperfusion (MIR) injury remain to be elucidated. MethodsIn this research, rodent and cellular models of MIR were used to detect the involvement and function of P2Y14 receptor, as well as the regulation of inflammatory signaling via P2Y14 receptor in neutrophils post-MIR. ResultsIn the early stage post MIR, the expression of P2Y14 receptor was upregulated in CD4+Ly-6G+ neutrophils. Additionally, the expression of P2Y14 receptor was highly induced in neutrophils subjected to uridine 5′-diphosphoglucose (UDP-Glu), which is proven to be secreted by cardiomyocytes during ischemia and reperfusion. Our results also showed the beneficial role of P2Y14 receptor antagonist PPTN in counteracting inflammation via promoting polarization of neutrophils to N2 phenotype in the infarct area of the heart tissue after MIR. ConclusionThese findings prove that the P2Y14 receptor is involved in the regulation of inflammation in the infarct area after MIR, and establish a novel signaling pathway concerning the interplay between cardiomyocytes and neutrophils in the heart tissue.

Elevated LDL Cholesterol Increases Microvascular Endothelial VWF and Thromboinflammation After Myocardial Infarction.

In reperfused myocardial infarction, VWF (von Willebrand factor)-mediated platelet adhesion contributes to impaired microvascular reflow and possibly also to postmyocardial infarction inflammation. We hypothesized that postischemic thromboinflammatory processes are worsened by elevated LDL (low-density lipoprotein) cholesterol. Myocardial ischemia-reperfusion or sham procedure was performed in wild-type mice and hyperlipidemic mice deficient for the LDL receptor and Apobec-1 (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-1; DKO [double knockout]). DKO subgroups were treated with N-acetylcysteine, which inhibits pro-adhesive VWF multimers or with recombinant ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs-13), which enzymatically cleaves endothelial surface-associated VWF. Myocardial contrast echocardiography perfusion imaging and molecular imaging for VWF, platelet glycoprotein Ibα, and leukocyte CD18 (cluster of differentiation) were performed 30 minutes post-reperfusion. Histology, infarct sizing, and echocardiography were performed at 1.5 or 72 hours; late echocardiography was performed at day 21. After ischemia-reperfusion, DKO compared with wild-type mice had ≈2-fold higher (P<0.05) risk area signal for microvascular platelet adhesion, VWF, and CD18; greater impairment in microvascular reflow, and 2-fold larger infarct size. Treatment of DKO mice with N-acetylcysteine and ADAMTS13 reduced molecular imaging signal for microvascular platelet adhesion, VWF, and CD18; improved early microvascular reflow; and reduced eventual infarct size. ADAMTS13 suppressed the postmyocardial infarction neutrophil and monocyte infiltration, enhanced the time-dependent recovery of left ventricular systolic function, and prevented late left ventricular remodeling. In reperfused myocardial infarction, elevated LDL cholesterol promotes thromboinflammation through excess microvascular endothelial VWF and platelet adhesion, resulting in less microvascular reflow and larger infarct size. In the presence of elevated LDL cholesterol, therapies that suppress endothelial-associated VWF can promote recovery of left ventricular function and protect against remodeling.

Research progress on the effects of novel hypoglycemic drugs in diabetes combined with myocardial ischemia/reperfusion injury.

Acute myocardial infarction (AMI) reperfusion is associated with ischemia/reperfusion (I/R) injury, which leads to enlarged myocardial infarction size, poor healing of the infarcted myocardium, and poor left ventricular remodeling, thus increasing the risk of major adverse cardiovascular events (MACEs). Diabetes increases myocardial susceptibility to I/R injury, decreases myocardial responsiveness to cardioprotective strategies, exacerbates myocardial I/R injury, and expands the infarct size of AMI, thereby increasing the incidence of malignant arrhythmias and heart failure. Currently, evidence regarding pharmacological interventions for diabetes combined with AMI and I/R injury is lacking. Traditional hypoglycemic drugs have a limited role in the prevention and treatment of diabetes combined with I/R injury. Current evidence suggests that novel hypoglycemic drugs may exert a preventive effect on diabetes combined with myocardial I/R injury, especially glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-dependent glucose transporter protein 2 inhibitors (SGLT2i), which may increase coronary blood flow, reduce acute thrombosis, attenuate I/R injury, decrease myocardial infarction size, inhibit structural and functional remodeling of the ischemic heart, improve cardiac function, and reduce the occurrence of MACEs of diabetes patients combined with AMI via mechanisms such as reduction of inflammatory response, inhibition of oxidative stress, and improvement of vascular endothelial function. This paper will systematically elaborate the protective role and molecular mechanisms of GLP-1 RA and SGLT2i in diabetes combined with myocardial I/R injury, aiming to provide clinical assistance.

Benign Late T Wave Inversion Post Coronary Artery Bypass Grafting: Case Report of Myocardial Reperfusion Sign Appearing Late on ECG

The onset of new T wave inversion (TWI) on an electrocardiogram (ECG) has always been considered an alarming sign of myocardial ischemia. Successful myocardial infarction reperfusion is indicated by the presence of early TWI after revascularization. We report a case of benign late precordial TWI post-coronary artery bypass grafting (CABG) with no evidence of myocardial ischemia.