Up-regulation of chemokine receptor type 4 expression in the ischemic reperfused heart by alcoholic extract of Cichorium intybus rescue the heart from ischemia injury in male rat.

OBJECTIVES: Cichorium intybus is used in traditional medicine for various diseases including heart disease. This study aimed at evaluating the chemokine receptor type 4 up-regulation and cardioprotective effects of hydroalcoholic extract of C. intybus in a rat model of ischemic reperfusion. METHODS: Animals in four groups of eight rats each received vehicle or one of three doses of C. intybus (50, 100 or 200 mg/kg/d) for 14 days. Then they were subjected to 30 min of ischemia followed by 7 days of reperfusion. At the end of the experiment, blood specimens were prepared for serum assays. The level of myocardium chemokine receptor type 4 was also measured using RT-PCR. KEY FINDINGS: Cichorium intybus (CI-50) improved infarct size, episodes of the ventricular ectopic beat, ventricular tachycardia, and duration of ventricular tachycardia, QTc shortening. It also stabilized the ST segment changes and increased heart rate during ischemia. The blood pressure decreased in CI-50 group in comparison to the control and CI-200 group. C. intybus increased serum superoxide dismutase and reduced lactate dehydrogenase activity, Cardiac Troponin I and malondialdehyde levels. C. intybus led to an increase in the expression of chemokine receptor type 4. CONCLUSIONS: These findings suggest that C. intybus administration before ischemia is able to induce cardioprotective effect against ischemic reperfusion injury, probably through chemokine receptor type 4 over-expression and antioxidant activity.

Cardioprotection by isosteviol derivate JC105: A unique drug property to activate ERK1/2 only when cells are exposed to hypoxia-reoxygenation.

In the present study, we have investigated potential cardioprotective properties of Isosteviol analogue we recently synthesized and named JC105. Treatment of heart embryonic H9c2 cells with JC105 (10 µM) significantly increased survival of cells exposed to hypoxia-reoxygenation. JC105 (10 µM) activated ERK1/2, DRP1 and increased levels of cardioprotective SUR2A in hypoxia-reoxygenation, but did not have any effects on ERK1/2, DRP1 and/or SUR2A in normoxia. U0126 (10 µM) inhibited JC105-mediated phosphorylation of ERK1/2 and DRP1 without affecting AKT or AMPK, which were also not regulated by JC105. Seahorse bioenergetic analysis demonstrated that JC105 (10 µM) did not affect mitochondria at rest, but it counteracted all mitochondrial effects of hypoxia-reoxygenation. Cytoprotection afforded by JC105 was inhibited by U0126 (10 µM). Taken all together, these demonstrate that (a) JC105 protects H9c2 cells against hypoxia-reoxygenation and that (b) this effect is mediated via ERK1/2. The unique property of JC105 is that selectively activates ERK1/2 in cells exposed to stress, but not in cells under non-stress conditions.

Direct Rivaroxaban-Induced Factor XA Inhibition Proves to be Cardioprotective in Rats.

BACKGROUND: Acute myocardial infarction is a leading cause of death worldwide. Though highly beneficial, reperfusion of myocardium is associated with reperfusion injury. While indirect inhibition of Factor Xa has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury, the underlying mechanism remains unclear. Our study sought to evaluate the effect of rivaroxaban (RIV), a direct inhibitor of Factor Xa, on myocardial I/R injury and determine its cellular targets. EXPERIMENTAL APPROACH: We used a rat model of 40-min coronary ligation followed by reperfusion. RIV (3 mg/kg) was given per os 1 h before reperfusion. Infarct size and myocardial proteic expression of survival pathways were assessed at 120 and 30 min of reperfusion, respectively. Plasmatic levels of P-selectin and von Willebrand factor were measured at 60 min of reperfusion. Cellular RIV effects were assessed using hypoxia-reoxygenation (H/R) models on human umbilical vein endothelial cells and on rat cardiomyoblasts (H9c2 cell line). KEY RESULTS: RIV decreased infarct size by 21% (42.9% vs. 54.2% in RIV-treated rats and controls respectively, P < 0.05) at blood concentrations similar to human therapeutic (387.7 ±â€Š152.3 ng/mL) levels. RIV had no effect on H/R-induced modulation of endothelial phenotype, nor did it alter myocardial activation of reperfusion injury salvage kinase and survivor activating factor enhancement pathways at 30 min after reperfusion. However, RIV exerted a cytoprotective effect on H9c2 cells submitted to H/R. CONCLUSIONS: RIV decreased myocardial I/R injury in rats at concentrations similar to human therapeutic ones. This protection was not associated with endothelial phenotype modulation but rather with potential direct cytoprotection on cardiomyocytes.

Acute reperfusion for ST-elevation myocardial infarction in New Zealand (2015-2017): patient and system delay (ANZACS-QI 29).

AIM: Prompt access to cardiac defibrillation and reperfusion therapy improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The study aim was to describe the 'patient' and 'system' delay in patients who receive acute reperfusion therapy for ST-elevation myocardial infarction (STEMI) in New Zealand. METHODS: In 2015-17, 3,857 patients who received acute reperfusion therapy were captured in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. 'Patient delay' is the time from symptom onset to first medical contact (FMC), and 'system delay' the time from FMC until reperfusion therapy (primary percutaneous coronary intervention (PCI) or fibrinolysis). RESULTS: Seventy percent of patients received primary PCI and 30% fibrinolysis. Of those receiving fibrinolysis, 122 (10.5%) received pre-hospital fibrinolysis. Seventy-seven percent were transported to hospital by ambulance. After adjustment, people who were older, male and presented to a hospital without a routine primary PCI service were less likely to travel by ambulance. Patient delay: The median delay was 45 minutes for ambulance-transported patients and 97 minutes for those self-transported to hospital, with a quarter delayed by >2 hours and >3 hours, respectively. Delay >1 hour was more common in older patients, Maori and Indian patients and those self-transported to hospital. System delay: For ambulance-transported patients who received primary PCI, the median time was 119 minutes. For ambulance-transported patients who received fibrinolysis, the median system delay was 86 minutes, with Maori patients more often delayed than European/Other patients. For patients who received pre-hospital fibrinolysis the median delay was 46 minutes shorter. For the quarter of patients treated with rescue PCI after fibrinolysis, the median needle-to-rescue time was prolonged-four hours. CONCLUSIONS: Nationwide implementation of the NZ STEMI pathway is needed to reduce system delays in delivery of primary PCI, fibrinolysis and rescue PCI. Ongoing initiatives are required to reduce barriers to calling the ambulance early after symptom onset.

Knock on the right door. How we are treating the patient with acute myocardial infarction / Bata na porta certa. Como estamos tratando o paciente com infarto agudo do miocárdio

Background: To reduce mortality of acute myocardial infarction, medical care must be provided within the first hours of the event. Objective: To identify the "front door" to medical care of acute coronary patients and the time elapsed between patients'admission and performance of myocardial reperfusion in the public health system of the city of Joinville, Brazil. Methods: The study was a retrospective analysis of the medical records of 112 consecutive patients diagnosed with acute myocardial infarction by coronary angiography. We identified the place of the first medical contact and calculated the time between admission to this place and admission to the referral hospital, as well as the time until coronary angiography, with or without percutaneous transluminal angioplasty. A descriptive analysis of data was made using mean and standard deviation, and a p < 0.05 was set as statistically significant. Results: Only 16 (14.3%) patients were admitted through the cardiology referral unit. Door-to-angiography time was shorter than 90 minutes in 50 (44.2%) patients and longer than 270 minutes in 39 (34.5%) patients. No statistically significant difference was observed in door-to-angiography time between patients transported directly to the referral hospital and those transferred from other health units (p < 0.240). Considering the time between pain onset and angiography, only 3 (2.9%) patients may have benefited from myocardial reperfusion performed within less than 240 minutes. Conclusion: Management of patients with acute myocardial infarction is not in conformity with current guidelines for the treatment of this condition. The structure of the healthcare system should be urgently modified so that users in need of emergency services receive adequate care in accordance with local conditions

Impacto clínico-funcional del traslado directo desde domicilio a un centro con servicio de hemodinamia en el infarto agudo de miocardio con elevación de ST / Clinical-functional impact of direct transfer from home to a center with hemodynamic service in acute myocardial infarction with ST elevation

Antecedentes: la demora en la reperfusión del infarto agudo de miocardio con elevación del ST (IAMCST) es un determinante mayor de su evolución clínica y funcional. Objetivo: analizar el impacto del traslado directo desde domicilio a un centro con hemodinamia sobre los tiempos de reperfusión y la evolución clínico-ecocardiográfica del IAMCST. Material y método: se diseñó un estudio prospectivo, observacional, que incluyó los pacientes con IAMCST recibidos en el servicio de hemodinamia del Instituto de Cardiología Intervencionista de Casa de Galicia (INCI) para angioplastia transluminal coronaria (ATC) primaria del 1º de febrero de 2016 al 30 de setiembre de 2016. Los pacientes se clasificaron en dos grupos: 1) traslado directo desde domicilio a servicio de hemodinamia y 2) traslado desde otro centro asistencial. Se evaluaron los tiempos dolor-primer contacto médico (PCM) y PCM-balón. Se comparó la evolución clínica, la fracción de eyección del ventrículo izquierdo (FEVI) y el score de contractilidad sectorial del VI a corto plazo (a las 48 horas tras el ingreso y al mes) entre ambos grupos. Resultados: se incluyeron 124 pacientes, 38 mujeres (31%), edad media 63,2±13,5 años. El tiempo PCM-balón representó el 54,7% del tiempo isquémico. Provenían de domicilio 51 pacientes (41%). El tiempo de reperfusión en el grupo 1 fue 284±241 min vs 498±309 min en el grupo 2 (p<0,001), mientras que el tiempo PCM-balón del grupo 1 fue 111±76,3 min vs 263±175,1 min del grupo 2, (p<0,001). No existieron diferencias significativas entre los grupos 1 y 2 en referencia a la FEVI medida al ingreso (49,5±9,33% vs 46,5±9,78%) y al mes (53,0±-8,5) vs (50,2±10,5). El score de contractilidad inicial fue menor en el grupo 1 (1,37±0,39) que en el grupo 2 (1,46±0,31) (p=0,029), mientras que no mostró diferencias significativas en el control al mes (1,23±0,26) vs 1,34±0,32. La mortalidad total fue de 12 pacientes (9,7%) y antes de las 48 horas, 8 pacientes (6,5%). La tasa de eventos cardíacos adversos mayores (ECAM: reinfarto, revascularización urgente, muerte y accidente cerebrovascular [ACV]) no difirió entre ambos grupos. Los pacientes que sufrieron ECAM presentaron mayor score de contractilidad inicial y menor FEVI inicial y al mes. Conclusión: la estrategia de traslado directo desde domicilio a un centro de hemodinamia se asocia con un menor tiempo isquémico total a expensas de un menor tiempo PCM-balón, menor tiempo PCM-puerta y con un mejor score de contractilidad segmentaria inicial.

Background: delayed reperfusion of acute myocardial infarction with ST elevation (STEMI) is a major determinant of its clinical and functional course. Objective: to analyze the impact of the direct transfer from home to a center with hemodynamic service on the reperfusion times and in the clinical and echocardiographic evolution of the STEMI. Method: a prospective, observational study was designed that included patients with STEMI received at the INCI hemodynamic service for primary coronary transluminal angioplasty (TCA) from 1st.February 2016 to 30th September 2016. Patients were classified in two groups: 1) direct transfer from home to hemodynamic service and 2) transfer from another care center. Pain-first medical contact (FMC) and FMC-device times were evaluated. The short-term clinical evolution, the left ventricular ejection fraction (LVEF) and left ventricular sector contractility score (at 48 hours post admission and at one month) were compared between both groups. Results: we included 124 patients, 38 (31%) women, mean age 63.2±13.5 years. FMC-device time accounted for 54.7% of ischemic time. 51 patients (41%) were direct transfer from domicile. The reperfusion time in group 1 was 284 ± 241 min vs. 498 ± 309 min in group 2 (p <0.001), while the FMC-device time of group 1 was 111 ± 76.3 min vs 263 ± 175.1 min of group 2, (p <0.001). There were no significant differences between groups 1 and 2 in relation to LVEF measured at admission (49.5 ± 9.33% vs. 46.5 ± 9.78%) and at one month (53.0 ± -8.5) vs. (50.2 ± 10.5). The initial contractility score was lower in group 1 (1.37 ± 0.39) than in group 2 (1.46 ± 0.31) (p = 0.029), whereas it did not show significant differences in control and at one month (1.23 ± 0.26). 1.34 ± 0.32. The total mortality was 12 patients (9.7%) and 8 patients (6.5%) before 48 hours. The rate of major adverse cardiac events (MACE) did not differ between the two groups. Conclusion: the strategy of direct transfer from home to a hemodynamic center is associated with a shorter total ischemic time at the expense of a shorter FMC-device time and a shorter FMC-door time and with a better segmental contractility score.

Intralesional versus intracoronary administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention in patients with acute coronary syndromes: A meta-analysis of randomized controlled trials.

BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) have been regarded as an adjuvant regimen to deal with no-reflow. However, whether intralesional (IL) administration of GPIs improves myocardial reperfusion without increasing bleeding in patients with acute coronary syndrome (ACS) compared with intracoronary (IC) administration has not been well addressed. Our meta-analysis aimed to evaluate the efficacy and safety of IL versus IC administration of GPIs for patients with ACS during percutaneous coronary intervention. METHODS: We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, and Cambridge Scientific Abstracts from January 2007 to May 2017. Thrombolysis in Myocardial Infarction (TIMI) 3 flow, corrected TIMI frame count (CTFC), and complete ST-segment resolution (>70%) were selected as the primary outcomes. Major adverse cardiac events (MACEs) were the secondary outcome, and major bleeding complications were the safety outcome. Data analysis was conducted using the Review Manager 5.3 software. RESULTS: Six randomized controlled trials were included in our meta-analysis. Compared with IC, IL obtained better results in terms of TIMI grade 3 flow [odds ratio (OR) 2.29; 95% confidence intervals (CIs) 1.31-4.01; P = .004], CTFC [weighted mean difference (WMD) -4.63; 95% CI -8.82 to -0.43; P = .03], and complete ST-segment resolution (OR 1.55; 95% CI 1.12-2.14; P = .008). There was a trend toward decreased MACE in the IL administration groups, which was not of statistical significance (OR 0.63; 95% CI 0.30-1.31; P = .22). No significant difference was found between the two groups in terms of in-hospital major bleeding events (OR 2.52; 95% CI .66 to 9.62; P = .18). CONCLUSION: IL administration yielded favorable outcomes in terms of myocardial tissue reperfusion as evidenced by the improved TIMI flow grade, CTFC, complete ST-segment resolution, and decreased MACE without increasing in-hospital major bleeding events. The IL administration of GPIs can be recommended as the preferred regimen to guard against no-reflow.

Baicalein Attenuates Lung Injury Induced by Myocardial Ischemia and Reperfusion.

Baicalein is an active component of Scutellaria baicalensis Georgi, which has traditionally been used to treat cardiovascular diseases in China. In this study, we investigated if treatment with baicalein can attenuate the lung injury induced by myocardial ischemia and reperfusion (I/R). Myocardial I/R, induced by a 40-min occlusion of the left anterior descending coronary artery and a 3-h reperfusion, significantly increased histological damage and the wet-to-dry weight ratio of lungs in rats. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive nuclei and caspase-3 activation was significantly increased in the lungs. Serum and bronchoalveolar lavage fluid levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interleukin-6 (IL-6) were significantly elevated, as were TNF-[Formula: see text] levels in the lung. Intravenous administration with baicalein at doses of 3, 10, and 30[Formula: see text]mg/kg for ten minutes before myocardial I/R significantly reduced histological damage, the wet-to-dry weight ratio, and apoptosis in the lung. Baicalein also significantly inhibited the increase in levels of TNF-[Formula: see text], IL-1[Formula: see text], and IL-6. Moreover, baicalein increased Bcl-2 and decreased p53, Bax, and cytochrome [Formula: see text] in lungs. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was increased, while the phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was decreased. In conclusion, treatment with baicalein attenuates the lung injury induced by myocardial I/R. The mechanisms might be related to the limiting of apoptosis, possibly via the inhibition of both the extrinsic and intrinsic pathways of apoptosis, including the inhibition of TNF-[Formula: see text] production and modulation of pro- and anti-apoptotic signaling elements.

Mitochondrial Bioenergetics During Ischemia and Reperfusion.

During ischemia and reperfusion (I/R) mitochondria suffer a deficiency to supply the cardiomyocyte with chemical energy, but also contribute to the cytosolic ionic alterations especially of Ca2+. Their free calcium concentration ([Ca2+]m) mainly depends on mitochondrial entrance through the uniporter (UCam) and extrusion in exchange with Na+ (mNCX) driven by the electrochemical gradient (ΔΨm). Cardiac energetic is frequently estimated by the oxygen consumption, which determines metabolism coupled to ATP production and to the maintaining of ΔΨm. Nevertheless, a better estimation of heart energy consumption is the total heat release associated to ATP hydrolysis, metabolism, and binding reactions, which is measurable either in the presence or the absence of oxygenation or perfusion. Consequently, a mechano-calorimetrical approach on isolated hearts gives a tool to evaluate muscle economy. The mitochondrial role during I/R depends on the injury degree. We investigated the role of the mitochondrial Ca2+ transporters in the energetic of hearts stunned by a model of no-flow I/R in rat hearts. This chapter explores an integrated view of previous and new results which give evidences to the mitochondrial role in cardiac stunning by ischemia o hypoxia, and the influence of thyroid alterations and cardioprotective strategies, such as cardioplegic solutions (high K-low Ca, pyruvate) and the phytoestrogen genistein in both sex. Rat ventricles were perfused in a flow-calorimeter at either 30 °C or 37 °C to continuously measure the left ventricular pressure (LVP) and total heat rate (Ht). A pharmacological treatment was done before exposing to no-flow I and R. The post-ischemic contractile (PICR as %) and energetical (Ht) recovery and muscle economy (Eco: P/Ht) were determined during stunning. The functional interaction between mitochondria (Mit) and sarcoplasmic reticulum (SR) was evaluated with selective mitochondrial inhibitors in hearts reperfused with Krebs-10 mM caffeine-36 mM Na+. The caffeine induced contracture (CIC) was due to SR Ca2+ release, while relaxation mainly depends on mitochondrial Ca2+ uptake since neither SL-NCX nor SERCA are functional under this media. The ratio of area-under-curves over ischemic values (AUC-ΔHt/AUC-ΔLVP) estimates the energetical consumption (EC) to maintain CIC. Relaxation of CIC was accelerated by inhibition of mNCX or by adding the aerobic substrate pyruvate, while both increased EC. Contrarily, relaxation was slowed by cardioplegia (high K-low Ca Krebs) and by inhibition of UCam. Thus, Mit regulate the cytosolic [Ca2+] and SR Ca2+ content. Both, hyperthyroidism (HpT) and hypothyroidism (HypoT) reduced the peak of CIC but increased EC, in spite of improving PICR. Both, CIC and PICR in HpT were also sensitive to inhibition of mNCX or UCam, suggesting that Mit contribute to regulate the SR store and Ca2+ release. The interaction between mitochondria and SR and the energetic consequences were also analyzed for the effects of genistein in hearts exposed to I/R, and for the hypoxia/reoxygenation process. Our results give evidence about the mitochondrial regulation of both PICR and energetic consumption during stunning, through the Ca2+ movement.

Timely Reperfusion in Stroke and Myocardial Infarction Is Not Correlated: An Opportunity for Better Coordination of Acute Care.

BACKGROUND: Timely reperfusion is critical in acute ischemic stroke (AIS) and ST-segment-elevation myocardial infarction (STEMI). The degree to which hospital performance is correlated on emergent STEMI and AIS care is unknown. Primary objective of this study was to determine whether there was a positive correlation between hospital performance on door-to-balloon (D2B) time for STEMI and door-to-needle (DTN) time for AIS, with and without controlling for patient and hospital differences. METHODS AND RESULTS: Prospective study of all hospitals in both Get With The Guidelines-Stroke and Get With The Guidelines-Coronary Artery Disease from 2006 to 2009 and treating ≥10 patients. We compared hospital-level DTN time and D2B time using Spearman rank correlation coefficients and hierarchical linear regression modeling. There were 43 hospitals with 1976 AIS and 59 823 STEMI patients. Hospitals' DTN times for AIS did not correlate with D2B times for STEMI (ρ=-0.09; P=0.55). There was no correlation between hospitals' proportion of eligible patients treated within target time windows for AIS and STEMI (median DTN time <60 minutes: 21% [interquartile range, 11-30]; median D2B time <90 minutes: 68% [interquartile range, 62-79]; ρ=-0.14; P=0.36). The lack of correlation between hospitals' DTN and D2B times persisted after risk adjustment. We also correlated hospitals' DTN time and D2B time data from 2013 to 2014 using Get With The Guidelines (DTN time) and Hospital Compare (D2B time). From 2013 to 2014, hospitals' DTN time performance in Get With The Guidelines was not correlated with D2B time performance in Hospital Compare (n=546 hospitals). CONCLUSIONS: We found no correlation between hospitals' observed or risk-adjusted DTN and D2B times. Opportunities exist to improve hospitals' performance of time-critical care processes for AIS and STEMI in a coordinated approach.

Impacto en la mortalidad de diferentes sistemas de asistencia en red para el tratamiento del infarto agudo de miocardio con elevación del segmento ST. La experiencia de España / Impact on mortality of different network systems in the treatment of ST-segment elevation acute myocardial infarction. The Spanish experience

Introducción y objetivos: Analizar la asociación entre la implementación de redes de reperfusión en el infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en las comunidades autónomas (CC.AA.) españolas, la tasa regional de intervención coronaria percutánea (ICP) y la mortalidad hospitalaria. Métodos: Se analizaron las altas hospitalarias del Sistema Nacional de Salud entre 2003 y 2012. El diagnóstico de IAMCEST y los procedimientos relacionados se codificaron mediante la Clasificación Internacional de Enfermedades. Las altas se clasificaron en 3 grupos: ICP (n = 116.621), trombolisis (n = 46.720) o sin reperfusión (n = 139.130). Resultados: La mortalidad no ajustada fue superior entre los pacientes no sometidos a ICP o fibrinolisis (17,3%) que entre los sometidos a ICP (4,8%) o fibrinolisis (8,6%) (p < 0,001). Se apreció un aumento en la tasa de ICP en el conjunto de CC.AA. (el 21,6% en 2003 frente al 54,5% en 2012; p < 0,001), con una reducción en la tasa de mortalidad estandarizada por riesgo (el 10,2% en 2003 y el 6,8% en 2012; p < 0,001). Se apreciaron diferencias significativas entre las tasas de ICP de las CC.AA. La implementación de redes de reperfusión se asoció con un aumento en la tasa de ICP del 50% (p < 0,001) y una reducción del 14% de la tasa de mortalidad estandarizada por riesgo (p < 0,001). Conclusiones: Entre 2003 y 2012 se produjo en España un aumento significativo de la tasa de ICP en el IAMCEST. La implementación de redes de reperfusión se asoció con un aumento en la tasa de ICP y una reducción de la mortalidad hospitalaria (AU)

Introduction and objectives: To analyze the association between the development of network systems of care for ST-segment elevation myocardial infarction (STEMI) in the autonomous communities (AC) of Spain and the regional rate of percutaneous coronary intervention (PCI) and in-hospital mortality. Methods: From 2003 to 2012, data from the minimum basic data set of the Spanish taxpayer-funded health system were analyzed, including admissions from general hospitals. Diagnoses of STEMI and related procedures were codified by the International Diseases Classification. Discharge episodes (n = 302 471) were distributed in 3 groups: PCI (n = 116 621), thrombolysis (n = 46 720), or no reperfusion (n = 139 130). Results: Crude mortality throughout the evaluation period was higher for the no-PCI or thrombolysis group (17.3%) than for PCI (4.8%) and thrombolysis (8.6%) (P < .001). For the aggregate of all communities, the PCI rate increased (21.6% in 2003 vs 54.5% in 2012; P < .001) with a decrease in risk-standardized mortality rates (10.2% in 2003; 6.8% in 2012; P < .001). Significant differences were observed in the PCI rate across the AC. The development of network systems was associated with a 50% increase in the PCI rate (P < .001) and a 14% decrease in risk-standardized mortality rates (P < .001). Conclusions: From 2003 to 2012, the PCI rate in STEMI substantially increased in Spain. The development of network systems was associated with an increase in the PCI rate and a decrease in in-hospital mortality (AU)

Association of Rapid Care Process Implementation on Reperfusion Times Across Multiple ST-Segment-Elevation Myocardial Infarction Networks.

BACKGROUND: The Mission: Lifeline STEMI Systems Accelerator program, implemented in 16 US metropolitan regions, resulted in more patients receiving timely reperfusion. We assessed whether implementing key care processes was associated with system performance improvement. METHODS AND RESULTS: Hospitals (n=167 with 23 498 ST-segment-elevation myocardial infarction patients) were surveyed before (March 2012) and after (July 2014) program intervention. Data were merged with patient-level clinical data over the same period. For reperfusion, hospitals were grouped by whether a specific process of care was implemented, preexisting, or never implemented. Uptake of 4 key care processes increased after intervention: prehospital catheterization laboratory activation (62%-91%; P<0.001), single call transfer protocol from an outside facility (45%-70%; P<0.001), and emergency department bypass for emergency medical services direct presenters (48%-59%; P=0.002) and transfers (56%-79%; P=0.001). There were significant differences in median first medical contact-to-device times among groups implementing prehospital activation (88 minutes implementers versus 89 minutes preexisting versus 98 minutes nonimplementers; P<0.001 for comparisons). Similarly, patients treated at hospitals implementing single call transfer protocols had shorter median first medical contact-to-device times (112 versus 128 versus 152 minutes; P<0.001). Emergency department bypass was also associated with shorter median first medical contact-to-device times for emergency medical services direct presenters (84 versus 88 versus 94 minutes; P<0.001) and transfers (123 versus 127 versus 167 minutes; P<0.001). CONCLUSIONS: The Accelerator program increased uptake of key care processes, which were associated with improved system performance. These findings support efforts to implement regional ST-segment-elevation myocardial infarction networks focused on prehospital catheterization laboratory activation, single call transfer protocols, and emergency department bypass.

Cardioprotection: Where to from here?

The size of the myocardial infarction remains an important therapeutic target, because heart attack size correlates with mortality and heart failure. In this era, myocardial infarct size is reduced primarily by timely reperfusion of the infarct related coronary artery. Whereas numerous pre-clinical studies have shown that certain pharmacologic agents and therapeutic maneuvers reduce myocardial infarction size greater than reperfusion alone, very few of these therapies have translated to successful clinical trials or standard clinical use. In this review we discuss both the recent successes as well as recent disappointments, and describe some of the newer potential therapies from the preclinical literature that have not yet been tested in clinical trials.

Carvedilol-Enriched Cold Oxygenated Blood Cardioplegia Improves Left Ventricular Diastolic Function After Weaning From Cardiopulmonary Bypass.

OBJECTIVES: To investigate whether adding carvedilol, a nonselective ß- and selective α1-receptor blocking agent with antioxidant properties, to oxygenated blood cardioplegia improves myocardial function after weaning from bypass. DESIGN: A randomized controlled study. SETTING: A university laboratory. PARTICIPANTS: Twenty anesthetized pigs, Norwegian Landrace. INTERVENTIONS: On cardiopulmonary bypass, cardiac arrest was induced with cold (12°C), oxygenated blood cardioplegia, enriched with carvedilol or vehicle, and repeated every 20 minutes. After 100 minutes, the heart was reperfused and weaned. MEASUREMENTS AND MAIN RESULTS: Left ventricular function was evaluated with pressure-volume loops, local myocardial systolic strain, and strain rate from Speckle tracking analysis and multilayer short-axis tissue Doppler Imaging. In the carvedilol group, the load-independent logarithmic end-diastolic pressure volume relationship, ß, decreased from 1 to 3 hours of reperfusion and was low, 0.028±0.004 v 0.042±0.007 (p<0.05) in controls at 3 hours, demonstrating improved left ventricular compliance. The diastolic relaxation constant τ was decreased, 28.9±0.6 ms v 34.6±1.3 ms (pg<0.035), and dP/dtmin was more negative,-1,462±145 mmHg/s v-1,105±105 mmHg/s (pg = 0.024), for carvedilol v control group. The systolic variables, preload recruitable stroke work and end-systolic pressure-volume relationship, did not differ between groups, neither did left ventricular systolic strain and strain rate. Myocardial oxidative stress, measured as tissue levels of malondialdehyde, was reduced by carvedilol, 0.19±0.01 compared to 0.24±0.01 nmol/mg (p = 0.004) in controls. CONCLUSIONS: Carvedilol added to blood cardioplegia improved diastolic cardiac function and reduced oxidative stress during the first 3 hours after reperfusion in a porcine model, with 100 minutes of cardioplegic arrest.

[Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level].

Objective: To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels. Methods: One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed. Results: Serum uric acid levels were decreased after treatment in both groups (all P<0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level (P<0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group (P<0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups (P>0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels (P<0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid (P<0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI (OR=1.01, 95% CI:1.01-1.11, P<0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) (P<0.01). Conclusion: High dose atorvastatin can decrease serum uric acid levels and improve reflow after PCI in patients with STEMI.

Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level / 浙江大学学报·医学版

To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels.One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed.Serum uric acid levels were decreased after treatment in both groups (all<0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level (<0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group (<0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups (>0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels (<0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid (<0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI (=1.01, 95%:1.01-1.11,<0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) (<0.01).High dose atorvastatin can decrease serum uric acid levels and improve reflow after PCI in patients with STEMI.

[Effect of aralosides to contraction function and calcium transient of ischemia/reperfusion myocardial cells].

To discuss the protective effect of aralosides (AS) on I/R-induced rat myocardial injury. The adult rat ventricular myocyte ischemia model was established through perfusion with sodium lactate perfusate and reperfusion with Ca(2+) -containing Tyrode's solution simulation. The cell contraction and ion concentration synchronization determination system was applied to detect the effect of AS on single I/R cell contraction and Ca2+ transients. According to the findings, AS could increase resting sarcomere length, contraction amplitude, ± dL/dt(max), calcium transient amplitude and speed of post-reperfusion myocardial cells (P < 0.05, P < 0.01), and decrease in time for achieving 90.0% of maximum relaxation, time for achieving peak value, resting calcium ratio, contraction period [Ca2+] i, time for achieving 50.0% of maximum relaxation and attenuation rate of intracellular calcium transient (P < 0.05, P < 0.01). Therefore, it is suggested that AS improved the post-reperfusion cell contraction and injury of calcium homeostasis.

Effect of aralosides to contraction function and calcium transient of ischemia/reperfusion myocardial cells / 中国中药杂志

To discuss the protective effect of aralosides (AS) on I/R-induced rat myocardial injury. The adult rat ventricular myocyte ischemia model was established through perfusion with sodium lactate perfusate and reperfusion with Ca(2+) -containing Tyrode's solution simulation. The cell contraction and ion concentration synchronization determination system was applied to detect the effect of AS on single I/R cell contraction and Ca2+ transients. According to the findings, AS could increase resting sarcomere length, contraction amplitude, ± dL/dt(max), calcium transient amplitude and speed of post-reperfusion myocardial cells (P < 0.05, P < 0.01), and decrease in time for achieving 90.0% of maximum relaxation, time for achieving peak value, resting calcium ratio, contraction period [Ca2+] i, time for achieving 50.0% of maximum relaxation and attenuation rate of intracellular calcium transient (P < 0.05, P < 0.01). Therefore, it is suggested that AS improved the post-reperfusion cell contraction and injury of calcium homeostasis.