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Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation. Nonetheless, current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models, which are not transferable or reproducible in large animal models due to different factors such as: (i) complex and varied features of human ischemic cardiac disease (ICD), which are challenging to mimic in animal models, (ii) significant differences in surgical techniques applied, and (iii) differences in cardiovascular anatomy and physiology between small versus large animals. This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury (IRI), as well as the different methods used to induce and assess IRI, and the obstacles faced in using large animals for translational research in the settings of cardiac IR.
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Daño por Reperfusión Miocárdica , Humanos , Animales , Daño por Reperfusión Miocárdica/veterinaria , Modelos Animales de EnfermedadRESUMEN
Ischemic cardiac or cerebrovascular disease (ICCD) survivors represent a subpopulation with a high cancer risk. Antiplatelet medications, such as aspirin, remain a fundamental therapy for the secondary prevention of ischemic attack in these patients. We conducted a population-based cohort study to investigate the association of long-term low-dose aspirin use with the risk of primary cancer in ICCD survivors. Patients aged ≥20 years with newly diagnosed ICCD (n = 98,519) between January 2000 and December 2013 were identified from the Taiwan National Health Insurance Research Database. The aspirin user and nonuser groups (each n = 24,030) were propensity-matched (1:1) for age, sex, comorbidities, prior medications, ICCD diagnosis year, and year of index dates. The incidence rate of primary cancer was significantly lower in the user group (6.49/1000 person-years) than in the nonuser group (14.04/1000 person-years). Multivariate Cox regression analysis indicated that aspirin use was an independent factor associated with a reduced risk of primary cancer (aHR (95% confidence interval) = 0.42 (0.38−0.45)) after adjustment. Kaplan−Meier curve analysis revealed that the cumulative incidence rate of primary cancer was significantly lower (p < 0.0001) in the user group than in the nonuser group over the 14-year follow-up period. Subgroup analyses demonstrated that this anticancer effect increased with duration of treatment and with similar estimates in women and men. In addition, aspirin use was associated with a reduced risk for seven out of the ten most common cancers in Taiwan. These findings suggest the anticancer effect of aspirin in ICCD survivors and provide information for assessing the benefit-to-risk profile of aspirin as an antiplatelet medication in these patients.
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RATIONALE & OBJECTIVE: The presence of calcified plaques in the coronary arteries is associated with cardiovascular mortality and is a hallmark of chronic kidney failure, but it is unclear whether this is associated with the same degree of coronary artery stenosis as in patients without kidney disease. We compared the relationship of coronary artery calcification (CAC) and stenosis between dialysis patients and patients without chronic kidney disease (CKD). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 127 dialysis patients and 447 patients without CKD with cardiovascular risk factors underwent cardiac computed tomography (CT), consisting of non-contrast-enhanced CT and CT angiography. CAC score and degree of coronary artery stenosis were assessed by independent readers. PREDICTOR: Dialysis treatment. OUTCOME: Association between calcification and stenosis. ANALYTICAL APPROACH: Logistic regression to determine the association between CAC score and the presence of stenosis in a matched cohort and, in the full cohort, testing for the interaction of dialysis status with this relationship. RESULTS: 112 patients were matched from each cohort, totaling 224 patients, using propensity scores for dialysis, balancing numerous cardiovascular risk factors. Median CAC score was 210 (IQR, 19-859) in dialysis patients and 58 (IQR, 0-254) in patients without CKD; 35% of dialysis patients and 36% of patients without CKD had coronary artery stenosis ≥ 50%. Per each 100-unit higher CAC score, the matched dialysis cohort had significantly lower ORs for stenosis than the non-CKD cohort, 0.67 (95% CI, 0.52-0.83) for stenosis ≥ 50% and 0.75 (95% CI, 0.62-0.90) for stenosis ≥ 70%. LIMITATIONS: No comparison with the gold standard fractional flow reserve. CONCLUSIONS: Dialysis patients have higher risk for coronary artery stenosis with higher CAC scores, but this risk is comparatively lower than in patients without CKD with similar CAC scores. In dialysis patients, a high CAC score can easily be found without significant stenosis. Our data enable "translation" of degree of calcification to the probability of coronary stenosis in dialysis patients.
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The association between air pollution and a wide-ranging spectrum of acute and chronic disorders-including cardiovascular diseases-is widely acknowledged. Exposure to airborne pollutants triggers harmful mechanisms such as oxidative stress and systemic inflammation, which lead to increased incidence of myocardial infarction, arterial hypertension, stroke, and heart failure. Sustained efforts have been made in recent years to discover how environmental exposures affect human health through epigenetic phenomena, such as DNA methylation, histone modifications and non-coding RNA-mediated gene regulation. This review summarizes the current evidences on the relationship between air pollution exposure, epigenetic alterations and cardiovascular impact, in view of present implications and future perspectives.
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Contaminación del Aire/efectos adversos , Enfermedades Cardiovasculares/genética , Epigenómica/tendencias , Contaminantes Atmosféricos , Contaminación del Aire/estadística & datos numéricos , Enfermedades Cardiovasculares/etiología , Metilación de ADN , Exposición a Riesgos Ambientales/efectos adversos , Epigénesis Genética , Epigenómica/métodos , Humanos , Hipertensión/etiología , Hipertensión/genética , Incidencia , Factores de RiesgoRESUMEN
Objective: To examine the prevalence of silent myocardial ischemia and fibrosis in antiphospholipid syndrome (APS), using stress cardiovascular magnetic resonance (CMR). Methods: Forty-four consecutive APS patients without prior cardiac disease (22 primary APS, 22 systemic lupus erythematosus (SLE)/APS, mean age 44 (12.9) years, 64% women) and 44 age/gender-matched controls were evaluated using CMR at 1.5 T. Steady-state free precession imaging for function assessment and adenosine stress-CMR for perfusion-fibrosis evaluation were employed. The myocardial perfusion reserve index (MPRI), and myocardial fibrosis expressed as late gadolinium enhancement (LGE), were evaluated. Coronary angiography was indicated in patients with LGE. Associations with APS characteristics, classic cardiovascular disease (CVD) risk factors, high-sensitivity CRP (hs-CRP) and high-sensitivity Troponin (hs-TnT) levels were tested. All patients were followed up for 12 months. Results: Median MPRI was significantly lower in APS patients versus controls [1.5 (0.9-1.9) vs. 2.7 (2.2-3.2), p < 0.001], independently of any LGE presence. LGE was detected in 16 (36.3%) patients versus none of controls (p < 0.001); 12/16 were subsequently examined with coronary angiography and only two of them had coronary artery lesions. In multivariable analysis, none of the APS-related and classic CVD risk factors, or hs-CRP and hs-TnT covariates, were significant predictors of abnormal MPRI or LGE. At the twelve month follow-up, three (6.8%) patients experienced coronary artery disease, notably those with the lowest MPRI values. Conclusions: Abnormal MPRI and LGE are common in asymptomatic APS patients, independently so of any APS-related and classic CVD risk factors, or coronary angiography findings in cases with LGE. Stress-CMR is a valuable tool to detect silent myocardial ischemia and fibrosis in APS.
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Objective: Despite the indubitable beneficial effect of exercise to prevent of cardiovascular diseases, there is still a lack of studies investigating the impact of exercise in non-ischemic dilated cardiomyopathy. Here, we investigated the impact of voluntary exercise on cardiac function in a mouse model of non-ischemic dilated cardiomyopathy (αMHC-MerCreMer:Sf/Sf), induced by cardiac-specific inactivation of the Serum Response Factor. Materials and Methods: Seven days after tamoxifen injection, 20 αMHC-MerCreMer:Sf/Sf mice were assigned to sedentary (n = 8) and exercise (n = 12) groups. Seven additional αMHC-MerCreMer:Sf/Sf mice without tamoxifen injection were used as control. The exercise group performed 4 weeks of voluntary running on wheel (1.8 ± 0.12 km/day). Cardiac function, myocardial fibrosis, and mitochondrial energetic pathways were then blindly assessed. Results: Exercised mice exhibited a smaller decrease of left ventricular (LV) fractional shortening and ejection fraction compared to control mice. This was associated with a lower degree of LV remodeling in exercised mice, as shown by a lower LV end-systolic intrerventricular septal and posterior wall thickness decrease from baseline values compared to sedentary mice. Moreover, exercised mice displayed a reduced gene expression of atrial and brain natriuretic factors. These benefits were associated by a reduced level of myocardial fibrosis. In addition, exercised mice exhibited a higher mitochondrial aconitase, voltage-dependent anion-selective channel 1 and PPAR gamma coactivators-1 alpha proteins levels suggesting that the increase of mitochondrial biogenesis and/or metabolism slowed the progression of dilated cardiomyopathy in exercised animals. Conclusions: In conclusion, our results support the role of voluntary exercise to improve outcomes in non-ischemic dilated heart failure (HF) and also support its potential for a routine clinical use in the future.
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Despite optimal interventional and medical therapy, ischemic heart disease is still an important cause of morbidity and mortality worldwide. Although not included in standard of care rehabilitation, stem cell therapy (SCT) could be a solution for prompting cardiac regeneration. Multiple studies have been published from the beginning of SCT until now, but overall no unanimous conclusion could be drawn in part due to the lack of appropriate end-points. In order to appreciate the impact of SCT, multiple markers from different categories should be considered: Structural, biological, functional, physiological, but also major adverse cardiac events or quality of life. Imaging end-points are among the most used - especially left ventricle ejection fraction (LVEF) measured through different methods. Other imaging parameters are infarct size, myocardial viability and perfusion. The impact of SCT on all of the aforementioned end-points is controversial and debatable. 2D-echocardiography is widely exploited, but new approaches such as tissue Doppler, strain/strain rate or 3D-echocardiography are more accurate, especially since the latter one is comparable with the MRI gold standard estimation of LVEF. Apart from the objective parameters, there are also patient-centered evaluations to reveal the benefits of SCT, such as quality of life and performance status, the most valuable from the patient point of view. Emerging parameters investigating molecular pathways such as non-coding RNAs or inflammation cytokines have a high potential as prognostic factors. Due to the disadvantages of current techniques, new imaging methods with labelled cells tracked along their lifetime seem promising, but until now only pre-clinical trials have been conducted in humans. Overall, SCT is characterized by high heterogeneity not only in preparation, administration and type of cells, but also in quantification of therapy effects.
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While ischemic heart disease in reproductive-age women is rare, cardiac disease is a leading cause of maternal mortality. In turn, coronary artery disease is one of the most common causes of maternal cardiac death. The incidence of coronary artery disease in pregnancy may be rising due to the increasing prevalence of comorbid risk factors. Diagnosis and clinical management of ischemic cardiac disease is largely similar in the pregnant and non-pregnant patient, and the majority of medications and diagnostic and interventional procedures are compatible with pregnancy with a few important exceptions. Care for ischemic cardiac disease in pregnancy may be suboptimal because: (1) diagnosis is delayed because many symptoms of ischemic cardiac disease are common in pregnancy, (2) a diagnostic workup is insufficiently thorough, and/or (3) consultants may be hesitant to perform diagnostic and interventional procedures in obstetric patients. Obstetric providers should be aware of the possibility of ischemic cardiac disease in pregnancy, particularly in patients with comorbid risk factors. If ischemic cardiac disease is suspected, a thorough workup should be performed.
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Anestesia Obstétrica/métodos , Ecocardiografía , Cardiopatías Congénitas/terapia , Atención Preconceptiva/métodos , Complicaciones Cardiovasculares del Embarazo/terapia , Embarazo de Alto Riesgo , Adulto , Femenino , Cardiopatías Congénitas/mortalidad , Cardiopatías Congénitas/fisiopatología , Humanos , Incidencia , Recién Nacido , Mortalidad Materna , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones Cardiovasculares del Embarazo/mortalidad , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Resultado del Embarazo , Prevalencia , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVE: Previous studies have shown that the metabolism of P2Y12 receptor blockers is influenced not only by CYP2C19 2 but also by PON1-Q192R alelles. We aimed to evaluate the impact of CYP2C19 2 and PON1-Q192R polymorphisms carriage in platelet reactivity and clinical outcome in patients with ischemic heart disease undergoing cardiac catheterization. PATIENTS AND METHOD: We recruited prospectively patients with acute coronary syndrome undergoing cardiac catheterization (n=247). We evaluated the genotype (CYP2C19 2, CYP2C19 17, PON1-Q192R) with TaqMan(®) assay and platelet aggregometry in all patients. We assessed both in and out-of-hospital events (unstable angina, periprocedural and spontaneous myocardial infarction, myocardial infarction, all-cause death, stent thrombosis and stroke) during follow-up. RESULTS: Carriers of CYP2C19 2 alleles showed a significant higher residual platelet reactivity (PRU, mean [SD], 252 [76] vs. 287 [74], P=.002). Carriers of PON1-Q192R CT(RQ) and TT(QQ) alleles and CYP2C19 17 did not present a different response to clopidogrel. In a multivariable setting for the prediction of platelet reactivity, the contribution of CYP2C19 2 was modest (Wald=7.5; odds ratio [OR] for ≥ 1 alelle 2=2,786, 95% confidence interval [95% CI] 1,337-5,808). Independent predictors were baseline hemoglobin levels (g/dL, OR .666, 95% CI .555-.801) and the use of statins (OR .376, 95% CI .162-.873). Body mass index was a risk factor (OR 1,074, CI 95% 1,005-1,148). Studied polymorphisms did not predict an adverse outcome. CONCLUSIONS: CYP2C19 2 polymorphism influenced moderately platelet reactivity but did not show an impact on clinical outcome in patients with acute coronary syndrome. Neither CYP2C19 17 nor PON1-Q192R polymorphisms showed an impact upon platelet reactivity or outcome.
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Síndrome Coronario Agudo/genética , Citocromo P-450 CYP2C19/fisiología , Inhibidores de Agregación Plaquetaria/farmacocinética , Agregación Plaquetaria/genética , Polimorfismo de Nucleótido Simple , Antagonistas del Receptor Purinérgico P2Y/farmacocinética , Ticlopidina/análogos & derivados , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/tratamiento farmacológico , Anciano , Alelos , Angina Inestable/epidemiología , Arildialquilfosfatasa/genética , Arildialquilfosfatasa/fisiología , Biotransformación/genética , Cateterismo Cardíaco , Clopidogrel , Trombosis Coronaria/epidemiología , Citocromo P-450 CYP2C19/genética , Femenino , Estudios de Seguimiento , Genotipo , Mortalidad Hospitalaria , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/farmacología , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Factores de Riesgo , Stents/efectos adversos , Accidente Cerebrovascular/epidemiología , Análisis de Supervivencia , Ticlopidina/farmacocinética , Ticlopidina/farmacología , Ticlopidina/uso terapéuticoRESUMEN
@#ObjectiveTo evaluate central nervous system function of patients with coronary cardiac diease by short latency somatosensory evoked potentials (SSEP).MethodsThe cerebral and spinal somatosensory evoked potentials were recorded by stimulating median nerve in 43 patients with coronary cardiac disease but without apparent nervous symptoms and 14 healthy control subjects.ResultsThe lactency periods and central conductive time of N13, N20 and P25 wave were significantly prolonged in patients with myocardial infarction (MI) or angina pectoris (AP) when compared with normal controls (P<0.05～0.001). The lactency periods and central conductive time of N20 and P25 wave recorded in MI patients were longer than those recorded in AP patients (P<0.01～0.001).ConclusionThe subclinical nervous damages in the central somatosensory pathway from spinal cord to cerebral cortex is present in patients with coronary cardiac disease especially myocardial infarction.