Over the past years, prevention and control of risk factors has begun to play an important role in the management of patients prone to develop atrial fibrillation (AF). A considerable number of risk factors that contribute to the creation of a predisposing substrate for AF has been identified over the years. Although certain AF risk factors such as age, gender, genetic predisposition, or race are unmodifiable, controlling modifiable risk factors may represent an invaluable tool in the management of AF patients. In the recent decades, numerous studies have evaluated the mechanisms linking different risk factors to AF, but the exact degree of atrial remodeling induced by each factor remains unknown. Elucidating these mechanisms is essential for initiating personalized therapies in patients prone to develop AF. The present review aims to provide an overview of the most relevant modifiable risk factors involved in AF occurrence, with a focus on the mechanisms by which these factors lead to AF initiation and perpetuation.
Alina Mărginean, Claudia Bănescu, Alina Scridon and Minodora Dobreanu
It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.
Alina Scridon, Emmanuelle Fouilloux-Meugnier, Emmanuelle Loizon, Marcel Perian, Sophie Rome, Claude Julien, Christian Barrès and Philippe Chevalier
Background: Aging is associated with significantly increased prevalence of cardiac arrhythmias, but transcriptional events that underlie this process remain to be established. To gain deeper insight into molecular mechanisms of aging-related cardiac arrhythmias, we performed mRNA expression analysis comparing atrial and ventricular myocardium from Wistar-Kyoto (WKY) rats of different ages. Methods: Atrial and ventricular sampling was performed in 3 groups (n=4 each) of young (14-week-old), adult (25-week-old), and aging (47-week-old) WKY rats. mRNA expressions of 89 genes involved in cardiac arrhythmogenicity were investigated using TaqMan Low Density Array analysis. Results: Of the 89 studied genes, 40 and 64 genes presented steady atrial and ventricular expressions, respectively. All genes differentially expressed within the atria of WKY rats were up-regulated with advancing age, mainly the genes encoding for various K+, Ca2+, Na+ channels, and type 6 collagen. Atrial expression levels of 19 genes were positively correlated with age. Ventricular transcriptomic analysis revealed a balance between up-regulated and down-regulated genes encoding for the same ion channels. Conclusion: Our results indicate the induction of an up-regulation transcriptional response in atrial but not ventricular myocytes with advancing age, suggesting that the two chambers undergo different molecular remodeling programs. Aging atria displayed a transcriptomic profile consistent with higher propensity to arrhythmias, including up-regulation of genes encoding for If, ICa-L, ICa-P, INa, outward K+ currents, and collagen, while ventricular transcriptome did not seem to be significantly altered by aging. These observations could explain the higher propensity to atrial than ventricular arrhythmias in the elderly.
M. Perian, M. Mărginean, D. Dobreanu and Alina Scridon
Objective: Cardioplegia is an important step to facilitate cardiac surgery while limiting intraoperative myocardial injury. Although recent advances in cardioplegic arrest methods have significantly contributed to better postoperative outcomes, there is still controversy regarding the optimal composition and temperature of the cardioplegic solution. Accordingly, we aimed to assess whether cold or lukewarm Sabax cardioplegia offer improved myocardial protection compared with the classical Krebs-Henseleit solution. Methods: The hearts of 40 male Wistar rats were isolated and submitted to constant-flow retrograde perfusion using a Langendorff perfusion apparatus. The hearts were randomly assigned to cold Krebs-Henseleit (K-H), cold Sabax, or lukewarm Sabax cardioplegia. The ECG, heart rates, and left ventricular systolic pressures (LVSP) were recorded pre- and post-cardioplegia. The time needed for cardioplegia induction and post-cardioplegia recovery were also noted. Results: Both cold and lukewarm Sabax cardioplegia insured faster induction and faster recovery following isothermic reperfusion compared to the standard K-H solution (both p< 0.01). With K-H cardioplegia, the hearts presented a 21.7% force loss after reperfusion (p< 0.001), whilst Sabax cardioplegia was associated with a slight increase in ventricular mechanical activity (3% LVSP increase with lukewarm Sabax cardioplegia, p< 0.001 and 2% LVSP increase with cold Sabax cardioplegia, p = 0.02). With Sabax cardioplegia the hearts displayed considerably less major arrhythmic events and presented less significant bradycardia. Conclusions: The present data suggest that Sabax cardioplegia may be superior to the classical cold crystalloid K-H solution in preserving mechanical activity of the heart and may provide superior protection against major arrhythmias.
Pintilie Irina, Scridon Alina and Șerban Răzvan Constantin
Introduction: The association between ST segment abnormalities, elevated cardiac enzymes, and chest pain is usually a marker of acute coronary injury. However, certain other pathologies can sometimes mimic acute coronary syndromes.
Case report: A 40-year-old Caucasian male, former smoker, with no other cardiovascular risk factors, presented to the Emergency Department for typical ischemic, prolonged chest pain. The ECG demonstrated inverted T waves in leads I, II, aVL, and V3 to V6. The patient presented high cardiac necrosis markers (troponin I 2.65 ng/ml). Based on these findings, the case was interpreted as non-ST segment elevation myocardial infarction, but coronary angiography excluded the presence of significant coronary lesions. The ventriculography showed an efficient left ventricle, with mild hypokinesia of the two apical thirds of the anterior left ventricular wall. Cardiac magnetic resonance imaging demonstrated areas of hypersignal on the T2-weighted imaging sequence in the left ventricular myocardium, suggestive for acute myocarditis. The patient was started on antiplatelet, beta-blocker, and angiotensin converting enzyme inhibitor, with favorable evolution.
Conclusion: This case underlines the polymorphic appearance of acute myocarditis, which can often mimic an acute coronary event.
Alina Scridon, Marcel Perian, Alina Marginean, Ciprian Fisca, Adriana Vantu, Doina Ghertescu, Philippe Chevalier and Razvan Constantin Serban
Background: Experimental models are essential for clarifying the pathogenesis of diabetes mellitus (DM). We aimed to provide an exhaustive description of clinical, biochemical, and hematologic features of rats with streptozotocin (STZ)-induced DM.
Methods: Wistar rats were assigned to control (n=14) or DM (n=17) groups. DM was induced using STZ (60 mg/kg, i.p.). If STZ failed to induce DM, rats were reinjected with a similar STZ dose. Bodyweight, 24-h food and water intake were measured weekly during 28 weeks. At the end of the study lipid profile, kidney function, and complete blood count were assessed.
Results: STZ induced DM in 58.82% of rats. The second STZ administration induced DM in 71.43% of the remaining rats. Diabetics presented progressive, but less significant bodyweight increase than controls, and higher food and water consumption. At the end of the study, diabetics presented higher white blood cells count, glucose, triglycerides, total and low-density lipoprotein cholesterol, and lower creatinine clearance than controls (all p≤0.02). No significant difference was observed between diabetics injected once and those that were reinjected, in any of the studied parameters.
Conclusions: This study provides one of the longest follow-ups of rats with STZ-induced type 1 DM, demonstrating that the STZ-diabetic rat replicates the most relevant clinical, biochemical, and hematologic features of human diabetes. The present data also indicate, for the first time, that rats with initial unsuccessful STZ administration can be safely reinjected, with outcomes similar to those seen in rats receiving a single injection.
Laszlo Hadadi, Ioana Sus, Eva Katalin Lakatos, Razvan Constantin Serban, Alina Scridon, Zoltan Demjen and Dan Dobreanu
Coronary chronic total occlusion (CTO) is caused by organized thrombi or atherosclerotic plaque progression. The presence of a CTO is an independent predictor of mortality in patients presenting with ST-segment elevation myocardial infarction (STEMI). Platelets have a crucial role in the pathophysiology of atherosclerosis. The aim of this retrospective study was to investigate platelet indices as predictors of CTO in patients with STEMI treated with primary percutaneous coronary intervention (pPCI). A total number of 334 patients admitted for STEMI between January 2011 and December 2013 were included and divided in two groups based on the presence of CTO (48 patients in CTO+ group, 286 patients in CTO-group). Platelet count, mean platelet volume (MPV), platelet distribution width (PDW), platelet-large cell ratio (P-LCR), lymphocyte and neutrophil count determined on admission were analyzed. MPV was larger in patients with CTO compared with patients without CTO (p=0.02), as were PDW (p=0.03) and P-LCR (p=0.01). Platelet-to-lymphocyte ratio (PLT/LYM) was lower in patients with CTO: 105.2 (75.86-159.1) compared to 137 (97-188.1), p<0.01. Receiver-operator characteristic curve analysis identified an area under the curve of 0.61 (95%CI=0.57-0.67, p< 0.01) for PLT/LYM in predicting the presence of a CTO, with a cut-off value at 97.73. Lower values than this were independent predictors of a CTO in multivariate logistic regression analysis, with an Odds Ratio of 2.2 (95%CI=1.15-4.20, p=0.02). Our results support the use of platelet indices and PLT/LYM as predictors of CTO in patients presenting with STEMI.
Zsombor Mathe, Razvan Constantin Serban, Irina Pintilie, Cristina Somkereki, Adina Hutanu and Alina Scridon
Introduction: The magnitude of the very early coronary artery bypass grafting (CABG)-related inflammatory response has been shown to influence post-CABG outcomes. However, the dynamics of the systemic inflammatory response to CABG beyond the very early postoperative phase and its relevance to clinical outcomes are not fully understood.
Methods: Circulating levels of several inflammatory markers were determined in 30 consecutive patients undergoing elective isolated on-pump CABG one day prior (D0-1), and 2 (D2) and 5 days post-CABG.
Results: CABG was associated with a significant increase in all studied inflammatory marker levels (all p<0.05 for D2 versus D0-1). D2 post-CABG IL-6 and IL-8 levels were both significantly positively correlated with extracorporeal circulation (ECC) and aortic clamping (AC) times (all p<0.05), whereas a weaker correlation was observed between D2 post-CABG IL-8 levels and total surgery time (r=0.42, p=0.02). In multiple regression analysis, D2 IL-8 levels independently predicted post-CABG kidney (p= 0.02) and liver (p = 0.04) dysfunction, as well as a sum of post-CABG major complications ≥2 (p = 0.04).
Conclusions: In this prospective study, longer duration of cardiopulmonary bypass caused a larger post-CABG inflammatory surge, whereas the duration of total CABG surgery had a less significant effect. IL-8 hyperresponders had greater risk of developing kidney and liver dysfunction and presented more major post-CABG complications. These data suggest that targeting the IL-8 pathway using antiinflammatory agents, or simply by shortening the duration of cardiopulmonary bypass could improve the in-hospital post-CABG outcomes in this population.
Grigorescu Bianca-Liana, Fodor Raluca Ştefania, Scridon Alina, Perian Marcel, Badea Iudita, Cioc Adrian Dan, Cotoi Ovidiu Simion, Copotoiu Sanda-Maria and Azamfirei Leonard
Objective: The assessment of systemic reperfusion injury and the contractile force of the peripheral muscles post-acute ischemia of the hind limbs in healthy versus diabetic ischemic preconditioned rats.
Method: The study included 16 Wistar rats divided into two groups: the control group and the diabetic ischemic preconditioned group. Acute ischemia was induced, followed by reperfusion. The assessment of reperfusion injury used biochemical, histopathological and functional determinations (peak tetanic tension-PTT, specific tension-ST).
Results: Ischemia-reperfusion injury was more severe in control group regarding creatine-kinase (CK) (CK1=470.13 IU/L versus CK2=230.88 IU/L, p=0.0001) and myoglobin (390.25 ng/mL versus 47.99 ng/mL, p=0.025). Cytolysis enzymes were significantly increased in diabetic preconditioned rats (Alanine aminotransferase ALAT1=46 IU/L, ALAT2=167.8 IU/L, p=0.02; Aspartate aminotransferase ASAT1=106 IU/L, ASAT2=237.5 IU/L, p=0.016). Functional assessment (PTT and ST) highlighted roughly equal values. A paradoxical response occurred in diabetic rats (the contractile force increased during the period of the stimulation). Histopathological findings showed that rhabdomyolysis was more severe in the control group, while inflammatory systemic response due to reperfusion injury was less expressed in diabetic ischemic preconditioned rats.
Conclusions: Ischemic preconditioning reduces the severity of reperfusion injury and allows the preservation of contractile muscle function in diabetic rats.
Alina Scridon, Marcel Perian, Teodor Grigoraş, Vasile Bogdan Halaţiu, Adriana Vântu, Alkora Ioana Balan, Ionela Alexandra Cosma, Asmaa Carla Barmou, Bogdan Andrei Finascu, Diana Lavinia Moldovan, Dan Alexandru Cozac and Răzvan Constantin Şerban