Decreasing levels of atmospheric pollution and simultaneous reduced number of cardiovascular hospital admissions and operations with improved results. Analysis of the Italian National Registries.

BACKGROUND: The aim of our study was to determine a correlation between decrease of levels of atmospheric pollution (as determined by air levels of Particulate Matters with a diameter equal or less to 2.5 microns) and reduced number of hospital admissions and operations for patients with common cardiovascular diseases in Italy. METHODS: We correlated number of hospital admissions and cardiovascular operations and atmospheric levels of PM.2.5 from 2015 to 2019 in Italy. This time interval was chosen because the possibility to analyze data about other established cardiovascular risk factors as reported by the European Union Eurostat. RESULTS: A statistically significant decrease of hospital admissions for cardiovascular and pulmonary emergencies was registered in Italy from 2015 to 2019 (p<0.01). The number also of cardiovascular operations showed a trend towards reduction with improved 30-days results, without reaching a statistically significant correlation (p =0.10). In the period 2015-2019, there was a steady decrease of atmospheric levels of pM2.5, either in urban or rural areas (p<0.01). The decrease of atmospheric levels of PMs2.5 started in 2010 and continued with a steady trend until the year 2019. In the period 2015-2019 exposure of the Italian population to established risk factors for cardiovascular diseases showed a small increase. The number of admissions and operations for non- cardiovascular and non-pulmonary diseases remained unchanged in the period 2015-2019. CONCLUSIONS: The findings of our study underline the possibility that decrease of atmospheric pollution may determine almost immediate decrease of cardiovascular and pulmonary diseases.

[Compatibility mechanism of Qishen Yiqi Dripping Pills for treatment of myocardial ischemia based on UPLC-Q-Exactive Orbitrap-MS and network pharmacology].

Clinical efficacy and mechanism of Qishen Yiqi Dripping Pills(QSYQ) have been well researched, but the compatibility mechanism underlying its therapeutic effect still requires further analysis. This study aims to explore the compatibility mechanism of QSYQ in treating myocardial ischemia. UPLC-Q-Exactive Orbitrap-MS technique was used to obtain the absorbed blood components of QSYQ. Target proteins of the absorbed components were collected and screened using TCMSP, TCMIP, and SwissTargetPrediction databases. Disease proteins related to myocardial ischemia were obtained through GeneCards, OMIM, and DisGeNET databases. Core targets and core components were obtained using online plotting software Venny 2.1.0, STRING, and Cytoscape 3.9.1 software. David database was used for GO functional annotation and KEGG pathway enrichment of core targets, obtaining the main pathways of QSYQ in treating myocardial ischemia and drawing visualized network diagrams. The compatibility mechanism was analyzed based on "component-target", "drug-pathway", and "PI3K-AKT" characteristic pathways, and molecular docking was used for validation. This study obtained 42 absorbed blood components of QSYQ, 556 component targets, 1 980 disease targets, 69 core targets, and 15 core components. QSYQ can exert therapeutic effects on myocardial ischemia by regulating proteins such as MAPK1, RELA, SRC, JUN, and STAT3, acting on signaling pathways such as HIF-1, PI3K-AKT, Toll-like, MAPK, VEGF, etc. The interaction network diagrams of "component-target" and "drug-pathway" preliminarily elucidated the synergy among the four drugs in this prescription at the level of targets and pathways. The PI3K-AKT characteristic pathway indicated that the sovereign drug Huangqi(Astragali Radix) and minister drug Danshen(Salviae Miltiorrhizae Radix et Rhizoma) could regulate most targets in this pathway, while the assistant drug Sanqi(Notoginseng Radix et Rhizoma) cooperated with Huangqi and Danshen on IL6 and AKT proteins, and the envoy drug Jiangxiang(Dalbergiae Odoriferae Lignum) acted on AKT and RXRA proteins, with all drugs acting synergistically on proteins such as AKT, RXRA, NFKB to regulate cell survival and promote angiogenesis. Molecular docking indicated that hydrogen bonding and hydrophobic interactions might be the main forms of action, also validating the distribution of binding energy of the PI3K-AKT signaling pathway. This study analyzed the compatibility connotation of QSYQ from multiple dimensions including drugs, components, targets, and pathways, providing reference basis for the study of the mechanism of action and compatibility rules of QSYQ.

The clinical value of noninvasive left ventricular myocardial work in the diagnosis of myocardial ischemia in coronary heart disease: a comparative study with coronary flow reserve fraction.

The prompt and precise identification of hemodynamically significant coronary artery lesions remains an ongoing challenge. This study investigated the diagnostic value of non-invasive global left ventricular myocardial work indices by echocardiography in functional status of coronary artery disease (CAD) patients with myocardial ischemia using fractional flow reserve (FFR) as the gold standard. A total of 77 consecutive patients with clinically suspected CAD were prospectively enrolled. All participants sequentially underwent echocardiography, invasive coronary angiography (ICA) and FFR measurement. According to the results of ICA, patients were divided into myocardial ischemia group (FFR ≤ 0.8, n = 27) and non-myocardial ischemia group (FFR > 0.8, n = 50). Myocardial work indices including global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), global positive work (GPW), global negative work (GNW), global systolic constructive work (GSCW) and global systolic wasted work (GSWW) were obtained by using the non-invasive left ventricular pressure strain loop (PSL) technique. Compared with the non-myocardial ischemia group, GWI, GCW, GPW and GSCW were significantly decreased in the myocardial ischemia group at either the 18-segment level or the 12-segment level (P < 0.001). At the 18-segment level, GWI < 1783.6 mmHg%, GCW < 1945.4 mmHg%, GPW < 1788.7 mmHg% and GSCW < 1916.5 mmHg% were optimal cut-off value to detect myocardial ischemia with an FFR ≤ 0.8. Global left ventricular myocardial work indices by echocardiography exhibited a good diagnostic value in patients with CAD and may have a good clinical significance for the screening of suspected myocardial ischemia.

Gastrodin exerts perioperative myocardial protection by improving mitophagy through the PINK1/Parkin pathway to reduce myocardial ischemia-reperfusion injury.

BACKGROUND: Although blood flow is restored after treatment of myocardial infarction (MI), myocardial ischemia and reperfusion (I/R) can cause cardiac injury, which is a leading cause of heart failure. Gastrodin (GAS) exerts protective effects against brain, heart, and kidney I/R. However, its pharmacological mechanism in myocardial I/R injury (MIRI) remains unclear. PURPOSE: GAS regulates autophagy in various diseases, such as acute hepatitis, vascular dementia, and stroke. We hypothesized that GAS could repair mitochondrial damage and regulate autophagy to protect against MIRI. STUDY DESIGN: Male C57BL/6 mice and H9C2 cells were subjected to I/R and hypoxia-reoxygenation (H/R) injury after GAS administration, respectively, to assess the impact of GAS on cardiomyocyte phenotypes, heart, and mitochondrial structure and function. The effect of GAS on cardiac function and mitochondrial structure in patients undergoing cardiac surgery has been observed in clinical practice. METHODS: The effects of GAS on cardiac structure and function, mitochondrial structure, and expression of related molecules in an animal model of MIRI were evaluated using immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy, western blotting, and gene sequencing. Its effects on the morphological, molecular, and functional phenotypes of cardiomyocytes undergoing H/R were observed using immunohistochemical staining, real-time quantitative PCR, and western blotting. RESULTS: GAS significantly reduces myocardial infarct size and improves cardiac function in MIRI mice in animal models and increases cardiomyocyte viability and reduces cardiomyocyte damage in cellular models. In clinical practice, myocardial injury was alleviated with better cardiac function in patients undergoing cardiac surgery after the application of GAS; improvements in mitochondria and autophagy activation were also observed. GAS primarily exerts cardioprotective effects through activation of the PINK1/Parkin pathway, which promotes mitochondrial autophagy to clear damaged mitochondria. CONCLUSION: GAS can promote mitophagy and preserve mitochondria through PINK1/Parkin, thus indicating its tremendous potential as an effective perioperative myocardial protective agent.

A Case of Tumoral Acute Coronary Syndrome - Case Report and Literature Review.

Cardiovascular disease and cancer constitute the most prevalent illnesses worldwide. Cancer patients show an increased risk of coronary artery disease not only due to shared cardiovascular risk factors, a pro-inflammatory and prothrombotic state induced by cancer itself, the cardiovascular toxicity of cancer therapy, or rarely, due to extrinsic compression of a coronary artery by the primary tumor or a metastatic lesion. Here, we present the case of a 59-year-old man with squamous cell carcinoma of the lung presented with asymptomatic diffuse ST segment depression and troponin T increase. Echocardiography revealed a large mass adjacent to the right atrium, atrioventricular groove, and basal segment of the anterior wall of the left ventricle, which the computed tomography scan showed to encase and probably compress the anterior descending coronary artery. Thus, the patient was diagnosed with acute coronary syndrome due to anterior descendent coronary artery compression by a neoplastic lung mass.

Recombinant human placental growth factor-2 in post-infarction left ventricular dysfunction: a randomized, placebo-controlled, preclinical study.

Placental growth factor (PlGF)-2 induces angio- and arteriogenesis in rodents but its therapeutic potential in a clinically representative post-infarction left ventricular (LV) dysfunction model remains unclear. We, therefore, investigated the safety and efficacy of recombinant human (rh)PlGF-2 in the infarcted porcine heart in a randomized, placebo-controlled blinded study. We induced myocardial infarction (MI) in pigs using 75 min mid-LAD balloon occlusion followed by reperfusion. After 4 w, we randomized pigs with marked LV dysfunction (LVEF < 40%) to receive continuous intravenous infusion of 5, 15, 45 µg/kg/day rhPlGF-2 or PBS (CON) for 2 w using osmotic pumps. We evaluated the treatment effect at 8 w using comprehensive MRI and immunohistochemistry and measured myocardial PlGF-2 receptor transcript levels. At 4 w after MI, infarct size was 16-18 ± 4% of LV mass, resulting in significantly impaired systolic function (LVEF 34 ± 4%). In the pilot study (3 pigs/dose), PIGF administration showed sustained dose-dependent increases in plasma concentrations for 14 days without systemic toxicity and was associated with favorable post-infarct remodeling. In the second phase (n = 42), we detected no significant differences at 8 w between CON and PlGF-treated pigs in infarct size, capillary or arteriolar density, global LV function and regional myocardial blood flow at rest or during stress. Molecular analysis showed significant downregulation of the main PlGF-2 receptor, pVEGFR-1, in dysfunctional myocardium. Chronic rhPIGF-2 infusion was safe but failed to induce therapeutic neovascularization and improve global cardiac function after myocardial infarction in pigs. Our data emphasize the critical need for properly designed trials in representative large animal models before translating presumed promising therapies to patients.

[Analysis of the unicentric registry of the Infarction Code program: retrospective cohort]. / Análisis del registro unicéntrico del programa Código Infarto: cohorte retrospectiva.

Background: Acute coronary syndrome (ACS) is the most serious manifestation of coronary heart disease. The Infarction Code (according to its initialism in Spanish, CI: Código Infarto) program aims to improve the care of these patients. Objective: To describe the clinical presentation and outcomes of CI program in a coronary care unit (CCU). Material and methods: A database of a CCU with 5 years of consecutive records was analyzed. Patients diagnosed with ACS were included. The groups with acute myocardial infarction with and without ST-segment elevation were compared using Student's t, Mann-Whitney U and chi-squared tests. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) of cardiovascular risk factors for mortality. Results: A total of 4678 subjects were analyzed, 78.7% men, mean age 63 years (± 10.7). 80.76% presented acute myocardial infarction with positive ST-segment elevation and fibrinolytic was granted in 60.8% of cases. Percutaneous coronary intervention was performed in 81.4% of patients, which was successful in 82.5% of events. Patients classified as CI presented mortality of 6.8% vs. 11.7%, p = 0.001. Invasive mechanical ventilation had an RR of 26.58 (95% CI: 20.61-34.3) and circulatory shock an RR of 20.86 (95% CI: 16.16-26.93). Conclusions: The CI program decreased mortality by 4.9%. Early fibrinolysis and successful coronary angiography are protective factors for mortality within CCU.

Introducción: el síndrome coronario agudo (SICA) es la manifestación más grave de la enfermedad coronaria. El programa Código Infarto (CI) tiene como objetivo mejorar la atención de estos pacientes. Objetivo: describir la presentación clínica y los resultados del programa CI de una unidad de cuidados coronarios (UCC). Material y métodos: se analizó una base de datos de una UCC con 5 años de registros consecutivos. Se incluyeron pacientes con diagnóstico de SICA. Se compararon los grupos con infarto agudo de miocardio con y sin elevación del segmento ST mediante las pruebas t de Student, U de Mann-Whitney y chi cuadrada. Se calculó el riesgo relativo (RR) y el intervalo de confianza del 95% (IC 95%) de los factores de riesgo cardiovascular para mortalidad. Resultados: se analizaron 4678 sujetos, 78.7% hombres, con media de edad de 63 años (± 10.7). El 80.76% presentó infarto agudo de miocardio con desnivel positivo del segmento ST y se otorgó fibrinolítico en el 60.8% de los casos. Se realizó intervencionismo coronario percutáneo en el 81.4% de los pacientes, el cual fue exitoso en el 82.5% de los eventos. Los pacientes catalogados como CI presentaron mortalidad del 6.8% frente a 11.7%, p = 0.001. La ventilación mecánica invasiva tuvo una RR de 26.58 (IC 95%: 20.61-34.3) y el choque circulatorio una RR de 20.86 (IC 95%: 16.16-26.93). Conclusiones: el programa CI disminuyó 4.9% la mortalidad. La fibrinólisis temprana y la angiografía coronaria exitosa son factores protectores para mortalidad dentro de la UCC.

The Role of Short-Chain Fatty Acids in Myocardial Ischemia-Reperfusion Injury.

PURPOSE OF REVIEW: This study aims to review the effects of short-chain fatty acids (SCFAs) in regulating the myocardial ischemia-reperfusion injury (MIRI). RECENT FINDINGS: Coronary heart disease (CHD) is a well-known leading cause of death and disability worldwide. Cardiac substrate metabolism plays the determinant role in assessing the severity of heart injury due to the abruptly shifted energy production during the MIRI. Fatty acids are the main energy fuels for the heart, which are classified into long-, medium- and short chain fatty acids by the length of carbon chain. SCFAs are the main metabolites derived from the anaerobic bacterial fermentation of fiber-rich diets, which are shown to play a protective role in cerebrovascular disease previously. Meanwhile, accumulating evidences suggest that SCFAs can also play a crucial role in cardiac energy metabolism. Results of various studies revealed the cardioprotective effects of SCFAs by displaying anti-inflammatory and anti-ferroptotic function, connecting gut-brain neural circuit and regulating the intestinal flora.

Zebrafish as an innovative model for exploring cardiovascular disease induction mechanisms and novel therapeutic interventions: a molecular insight.

Cardiovascular disease (CVD) is a common cardiac disorder that leads to heart attacks, strokes, and heart failure. It is primarily characterized by conditions that impact the heart and blood arteries, including peripheral artery disease, arrhythmias, atherosclerosis, myocardial ischemia, congenital heart abnormalities, heart failure, rheumatic heart disease, hypertension, and cardiomyopathies. These conditions are mainly effect the heart and blood vessels, causing blockages or weakened pumping, due to severe hereditary and environmental factors. The frequency of CVD is rising significantly as life expectancy increases. Despite this, no effective treatment or management for its symptoms has been found. One of the most difficult obstacles to overcome, is finding a suitable animal model for drug screening and drug development. Although rodents, mice, swine, and mammals serve as the basis for most animal models of cardiovascular disease, no model accurately captures the epidemiology of the condition. Zebrafish (Danio rerio) have drawn the interest of the international scientific community due to certain shortcomings of the previously discussed animal models because they are smaller, less costly, and have an incredibly high rate of reproduction. This review article emphasizes the significance of using zebrafish as an animal model to investigate the possible facets of cardiovascular disease. Moreover, the ultimate purpose of this review article is to establish the advantages of employing zebrafish over other animal models and to investigate the boundaries of using zebrafish to study human disease. Furthermore, the mechanisms of cardiovascular diseases induction in zebrafish were covered to improve understanding for readers. Finally, the analysis of cardiotoxicity using Zebra fish model, is also explained. In order to stop the health index from deteriorating, the current study also covers some innovative, effective, and relatively safer treatments for treatment and management of cardiotoxicity.

Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome, Reversible Cerebral Vasoconstriction Syndrome and Myocardial Ischemia: A Case Report and Review.

Acute intermittent porphyria is a rare autosomal dominant metabolic disorder. It can affect the autonomic, peripheral, and central nervous system. The present study reports on the case of 28-year-old Chinese female patient with posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome and myocardial ischemia which have been very rarely reported in patients with acute intermittent porphyria.

Mitochondria-targeted sonodynamic modulation of neuroinflammation to protect against myocardial ischemia‒reperfusion injury.

Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.

Reproducibility of a single-volume dynamic CT myocardial blood flow measurement technique: validation in a swine model.

BACKGROUND: We prospectively assessed the reproducibility of a novel low-dose single-volume dynamic computed tomography (CT) myocardial blood flow measurement technique. METHODS: Thirty-four pairs of measurements were made under rest and stress conditions in 13 swine (54.3 ± 12.3 kg). One or two acquisition pairs were acquired in each animal with a 10-min delay between each pair. Contrast (370 mgI/mL; 0.5 mL/kg) and a diluted contrast/saline chaser (0.5 mL/kg; 30:70 contrast/saline) were injected peripherally at 5 mL/s, followed by bolus tracking and acquisition of a single volume scan (100 kVp; 200 mA) with a 320-slice CT scanner. Bolus tracking and single volume scan data were used to derive perfusion in mL/min/g using a first-pass analysis model; the coronary perfusion territories of the left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA) were automatically assigned using a previously validated minimum-cost path technique. The reproducibility of CT myocardial perfusion measurement within the LAD, LCx, RCA, and the whole myocardium was assessed via regression analysis. The average CT dose index (CTDI) of perfusion measurement was recorded. RESULTS: The repeated first (Pmyo1) and second (Pmyo2) single-volume CT perfusion measurements were related by Pmyo2 = 1.01Pmyo1 - 0.03(ρ = 0.96; RMSE = 0.08 mL/min/g; RMSE = 0.07 mL/min/g) for the whole myocardium, and by Preg2 = 0.86Preg1 + 0.13(ρ = 0.87; RMSE = 0.31 mL/min/g; RMSE = 0.29 mL/min/g) for the LAD, LCx, and RCA perfusion territories. The average CTDI of the single-volume CT perfusion measurement was 10.5 mGy. CONCLUSION: The single-volume CT blood flow measurement technique provides reproducible low-dose myocardial perfusion measurement using only bolus tracking data and a single whole-heart volume scan. RELEVANCE STATEMENT: The single-volume CT blood flow measurement technique is a noninvasive tool that reproducibly measures myocardial perfusion and provides coronary CT angiograms, allowing for simultaneous anatomic-physiologic assessment of myocardial ischemia. KEY POINTS: A low-dose single-volume dynamic CT myocardial blood flow measurement technique is reproducible. Motion misregistration artifacts are eliminated using a single-volume CT perfusion technique. This technique enables combined anatomic-physiologic assessment of coronary artery disease.

The prognostic impact of unplanned invasive coronary angiography following coronary artery bypass grafting.

OBJECTIVES: Myocardial ischaemia following coronary artery bypass grafting (CABG) is a potentially devastating complication. Nevertheless, the incidence, aetiology, and prognostic relevance of unplanned CAG remain understudied. We aimed to investigate the prevalence and outcome of patients undergoing urgent, unplanned coronary angiography in the postoperative period following CABG. METHODS: We screened all patients undergoing isolated elective CABG in an academic referral centre between 2016-2021 and identified patients undergoing unplanned CAG (uCAG) within 30 days of surgery. Within uCAG patients, a distinction was made between patients undergoing re-revascularization (REV) and patients receiving conservative management (CON). The primary outcomes were 30-day mortality and unadjusted and adjusted long-term survival. Secondary outcomes were the indication for and prevalence of uCAG and urgent revascularization. RESULTS: Of the 1918 patients undergoing isolated CABG, 78 individuals needed uCAG (4.1%), of which 45 underwent immediate revascularization (REV-group; 2.3% overall, 57% within the uCAG group, median age 69.9 years) and 33 were treated conservatively (CON-group; 1.7% overall, 42% within the uCAG group, median age 69.1 years). Patients undergoing uCAG (n = 78) had a higher 30-day mortality than patients not undergoing uCAG (n = 1840, 30-day mortality: 9.0% vs 0.4%, p < 0.001). Long-term survival was significantly decreased in patients undergoing uCAG in both unadjusted (hazard ratio [HR] 2.20, 95% CI 1.30-3.73), and EuroSCORE-, age-, and sex-adjusted models (HR uCAG 2.03, 95% CI 1.16-3.56). CONCLUSIONS: Unplanned postoperative CAG is performed in 4.1% of isolated CABG procedures, and patients in need of such urgent invasive evaluation are subjected to decreased short- and long-term survival.

Brown adipose tissue-derived FGF21 mediates the cardioprotection of dexmedetomidine in myocardial ischemia/reperfusion injury.

Brown adipose tissue (BAT) plays a critical role in regulating cardiovascular homeostasis through the secretion of adipokines, such as fibroblast growth factor 21 (FGF21). Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist with a protection against myocardial ischemia/reperfusion injury (MI/RI). It remains largely unknown whether or not BAT-derived FGF21 is involved in DEX-induced cardioprotection in the context of MI/RI. Herein, we demonstrated that DEX alleviated MI/RI and improved heart function through promoting the release of FGF21 from interscapular BAT (iBAT). Surgical iBAT depletion or supplementation with a FGF21 neutralizing antibody attenuated the beneficial effects of DEX. AMPK/PGC1α signaling-induced fibroblast growth factor 21 (FGF21) release in brown adipocytes is required for DEX-mediated cardioprotection since blockade of the AMPK/PGC1α axis weakened the salutary effects of DEX. Co-culture experiments showed that DEX-induced FGF21 from brown adipocytes increased the resistance of cardiomyocytes to hypoxia/reoxygenation (H/R) injury via modulating the Keap1/Nrf2 pathway. Our results provided robust evidence that the BAT-cardiomyocyte interaction is required for DEX cardioprotection, and revealed an endocrine role of BAT in DEX-mediating protection of hearts against MIRI.

Noninvasive Coronary Physiological Assessment Derived From Computed Tomography.

Identifying functional significance using physiological indexes is a standard approach in decision-making for treatment strategies in patients with coronary artery disease. Recently, coronary computed tomography angiography-based physiological assessments, such as computed tomography perfusion and fractional flow reserve derived from coronary computed tomography angiography (FFR-CT), have emerged. These methods have provided incremental diagnostic values for ischemia-causing lesions over anatomical stenosis defined solely by coronary computed tomography angiography. Clinical data have demonstrated their prognostic value in the prediction of adverse cardiovascular events. Several randomized controlled studies have shown that clinical use of FFR-CT can reduce unnecessary invasive procedures compared to usual care. Recent studies have also expanded the role of FFR-CT in defining target lesions for revascularization by acquiring noninvasive lesion-specific hemodynamic indexes like ΔFFR-CT. This review encompasses the current evidence of the diagnostic and prognostic performance of computed tomography-based physiological assessment in defining ischemia-causing lesions and adverse cardiac events, its clinical impact on treatment decision-making, and implications for revascularization.

Enhanced External Counterpulsation Outcomes Study: Retrospective Analyses of Data Obtained from Patients at a Single Medical Center in United States.

The aim was to explore the effectiveness of enhanced external counterpulsation (EECP) therapy in patients with severe angina pectoris/ chronic heart failure symptoms, who were not suitable candidates for invasive treatment. This retrospective study employed a comprehensive methodology that includes individualized treatment, continuous monitoring, and thorough pre- and postprogram evaluations to assess the efficacy of EECP therapy. The standard protocol involved 35 one-hour treatments, with flexibility for extensions based on therapeutic progress. When pre- and posttreatment results were analyzed, EECP improved the original functional class compared with pretreatment. The mean difference in the functional class was 1.32 (0.92), p < 0.0001. Six-minute walk (6MW) distance improved from 383.6 m (110.24) to 423.1 m (121.50) with mean difference of 37.1 (44.99), p < 0.0001. Duke Activity Status Index (DASI) score improved from 3.9 (2.75) to 6.0 (4.17) with mean difference of 2.16 (3.8), p < 0.0001. Training metabolic equivalents (METs) improved from 3.0 (0.74) to 4.0 (1.57) with mean difference of 1.04 (1.2), p < 0.0001. Weekly anginal events decreased from 13.1 (13.19) to 3.2 (7.38) with mean difference of -9.78 (11.7), p < 0.0001. EECP resulted in improvement of angina pectoris functional class, the 6MW distance, reduction in the number of hospitalizations in first year posttreatment, a significant decrease in sublingual nitroglycerin use, improvement of systolic and diastolic blood pressure, and improvement of DASI score.

TRPC6 regulates necroptosis in myocardial ischemia/reperfusion injury via Ca2+/CaMKII signaling pathway.

Myocardial ischemia-reperfusion injury (MIRI) frequently complicates postoperative cardiovascular disease treatment. Necroptosis, a cell death mechanism similar to apoptosis, is regulated by specific signaling pathways and plays an important role in MIRI. Receptor-interacting protein 3 (RIP3), a key protein regulating necroptosis during MIRI, directly phosphorylates calmodulin-dependent protein kinase II (CaMKII). Leading to mitochondrial permeablity transition pore (mPTP) opening and inducing necroptosis. Transient receptor potential canonical channel 6 (TRPC6) regulats Ca2+ entry, is linked to CaMKII as an important upstream effector. However, the connection between TRPC6 and MIRI necroptosis remains unclear. The study aimed to investigate the relationship between TRPC6 and MIRI necroptosis, with a specific focus on elucidating the role of TRPC6 in regulating CaMKII phosphorylation during cardiac necroptosis via Ca2+ modulation. METHODS AND RESULTS: The experiment used wild-type (WT) and TRPC6 knockout (TRPC6-/-) mice for I/R model construction, and H9c2 myocardial cell line for H/R model. After ischemia-reperfusion (I/R), TRPC6 protein levels in mice significantly increased, exacerbating myocardial injury, infarct size (IS), and cardiac function in WT mice. In contrast, TRPC6 knockout attenuated myocardial injury, IS, and improved cardiac function. The results showed a significant correlation between changes in CaMKII and TRPC6. TRPC6 knockout led to decreased intracellular calcium levels, CaMKII phosphorylation, reactive oxygen species levels, mPTP opening, and improve mitochondrial structure. CONCLUSION: I/R upregulates TRPC6, which mediates Ca2+ entry and CaMKII phosphorylation, exacerbates oxidative stress, and induces necroptosis. These findings suggest a potential therapeutic avenue for mitigating MIRI by targeting TRPC6.

Panax notoginseng saponins dually modulates autophagy in gastric precancerous lesions complicated with myocardial ischemia-reperfusion injury model through the PI3K/AKT/mTOR pathway.

Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS.

Protective effects of fructose-1,6-bisphosphate postconditioning on myocardial ischemia-reperfusion injury in patients undergoing valve replacement：a randomized, double-blind, placebo-controlled clinical trial.

Legend of Graphical Abstract: The figure describes the serum CK-MB concentrations in the FDP and NS groups at 4, 24, 48, and 72 h postoperatively. OBJECTIVES: Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1, 6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. METHODS: Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), alpha-hydroxybutyrate dehydrogenase (α-HBDH) and cardiac troponin I (cTnI), the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, ICU and postoperative hospitalization. RESULTS: Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, LDH, CK, cTnI, α-HBDH and hs-CRP at T1∼4 were lower in the FDP group than in the NS group (P < 0.001). Compared with the NS group, the dosage of dopamine administered 1∼90min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P < 0.001, P < 0.001 and P = 0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group （median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm）(P < 0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group（50.3 [12.3] min vs 34.6 [6.9] min） (P < 0.001). CONCLUSIONS: The fructose-1, 6-bisphosphate postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation.

Trimetazidine attenuates Ischemia/Reperfusion-Induced myocardial ferroptosis by modulating the Sirt3/Nrf2-GSH system and reducing Oxidative/Nitrative stress.

Ferroptosis is a newly defined mode of cellular demise. The increasing investigation supports that ferroptosis is a crucial factor in the complex mechanisms of myocardial ischemia-reperfusion (I/R) injury. Hence, targeting ferroptosis is a novel strategy for treating myocardial injury. Although evidence suggests that trimetazidine (TMZ) is potentially efficacious against myocardial injury, the exact mechanism of this efficacy is yet to be fully elucidated. This study aimed to determine whether TMZ can act as a ferroptosis resistor and affect I/R-mediated myocardial injury. To this end, researchers have constructed in vitro and in vivo models of I/R using H9C2 cardiomyocytes, primary cardiomyocytes, and SD rats. Here, I/R mediated the onset of ferroptosis in vitro and in vivo, as reflected by excessive iron aggregation, GSH depletion, and the increase in lipid peroxidation. TMZ largely reversed this alteration and attenuated cardiomyocyte injury. Mechanistically, we found that TMZ upregulated the expression of Sirt3. Therefore, we used si-Sirt3 and 3-TYP to interfere with Sirt3 action in vitro and in vivo, respectively. Both si-Sirt3 and 3-TYP partly mitigated the inhibitory effect of TMZ on I/R-mediated ferroptosis and upregulated the expression of Nrf2 and its downstream target, GPX4-SLC7A11. These results indicate that TMZ attenuates I/R-mediated ferroptosis by activating the Sirt3-Nrf2/GPX4/SLC7A11 signaling pathway. Our study offers insights into the mechanism underlying the cardioprotective benefits of TMZ and establishes a groundwork for expanding its potential applications.