[Comment] The challenges of planetary mental health in the COVID-19 era.

As the focus of the COVID-19 crisis is gradually taken away from emergency healthcare needs, increased attention is warranted on the psychological impact of the pandemic on a global level. Existing guidance on managing the COVID-19 related distress needs to be better informed by upcoming larger-scale research. Applying e-Health can be useful in dealing with the immediate psychological needs, while developing strategies to identify vulnerable populations and shifting the provision of mental health and social care to community services need to be prioritised when looking at the future. Focusing on global mental health during this universal crisis is an opportunity for promoting a more compassionate and less discriminating society

Atorvastatin Therapy during the Peri-Infarct Period Attenuates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction

Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dtmax, end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis

Asymmetric dimethylarginine (ADMA) and other endogenous nitric oxide synthase (NOS) inhibitors as an important cause of vascular insulin resistance

Asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA) are important endogenous endothelial nitric oxide synthase (eNOS) inhibitors. Studies have shown that patients with insulin resistance have elevated plasma levels of ADMA. Moreover, ADMA levels have a prognostic value on long-term outcome of patients with coronary artery disease. Insulin resistance, a disorder associated to inadequate biological responsiveness to the actions of exogenous or endogenous insulin, is a metabolic condition, which exists in patients with cardiovascular diseases. This disorder affects the functional balance of vascular endothelium via changes of nitric oxide (NO) metabolism. Nitric oxide is produced in endothelial cells from the substrate L-arginine via eNOS. Elevated ADMA levels cause eNOS uncoupling, a mechanism which leads to decreased NO bioavailability and increased production of hydrogen peroxide. According to clinical Studies, the administration of L-arginine to patients with high ADMA levels improves NO synthesis by antagonizing the deleterious effect of ADMA on eNOS function, although in specific populations such as diabetes mellitus, this might even been harmful. More studies are required in order to certify the role of NOS inhibitors in insulin resistance and endothelial dysfunction. It is still difficult to say whether increased ADMA levels in certain populations is only a reason or the result of the molecular, alterations, which take place in vascular disease states

Association of inflammatory markers with angiographic severity and extent of coronary artery disease

Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate many of the stages of atheroma development, from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. Several systemic inflammatory markers reflect different degrees of inflammation and have been indicated as independent risk factors in cardiovascular disease, especially in unstable coronary syndromes. However, whether elevated levels of circulating inflammatory markers play a role in the extent and severity of atherosclerosis remains controversial. The present review summarizes our current understanding of the relationship between inflammatory markers and the presence and extent of coronary atherosclerosis, in order to assess the potential utility of these markers in identifying patients with higher levels of atherosclerotic burden. © 2009 Elsevier Ireland Ltd. All rights reserved

Heart regeneration: what cells to use and how?

Coronary artery disease (CAD) is the leading cause of death in modern societies. Recent achievements in the treatment of CAD including statins, ACE inhibitors, beta blockers, and interventional procedure improved the outcome of patients with CAD, but this conventional approach failed to control cardiovascular mortality. Nowadays, cells (stem cells) and their potential role in managing patients with heart disease is a field of intensive research. Various types of cells have been used for transplantation targeting heart regeneration, including bone marrow cells (BMCs), cardiac stem cells (CSCs), endothelial progenitor cells (EPCs), skeletal myoblasts (SMs), adipose stroma tissue cells (ATSCs), mesenchymal cells (MCs), and embryonic stem cells (ESCs). Several routes have been used to deliver these cells to human myocardium or to the coronary circulation such as, intracoronary injection, intravenous infusion, direct injection into the ventricular wall, or transepicardial/transendocardial infusions. Although the results of the recent clinical trials in this area are rather conflicting, these therapeutic approaches seem to be promising for the treatment of ischemic heart disease

L-Arginine, the substrate for NO synthesis: an alternative treatment for premature atherosclerosis?

L-Arginine is the substrate of endothelial nitric oxide synthase (eNOS) and the main precursor of nitric oxide (NO) in the vascular endothelium. L-Arginine improves endothelial function in patients with hypercholesterolemia, hypertension and smokers, while its role in diabetes remains unclear. Oral supplementation of L-arginine leads to a significant improvement of endothelium-dependent forearm vasodilation in hypercholesterolemic patients, while intravenous infusion of L-arginine improves endothelial function in healthy smokers. L-Arginine has anti-hypertensive properties, although its effects on endothelial function in hypertensive patients needs further evaluation. In conclusion, L-arginine administration may be useful in patients with premature atherosclerosis

Inflammatory Biomarkers Predicting Events in Atherosclerosis

Recent evidence suggests that vascular inflammation plays important role in the pathogenesis and the clinical evolution of atherosclerosis. Several circulating inflammatory biomarkers such as acute phase proteins, adhesion molecules and pro-inflammatory cytokines along with biomarkers, proposed the last few years, have clarified the role of inflammation in atherosclerosis. In particular a number of studies have focused on the positive predictive role of C-reactive protein in populations without prior cardiovascular disease. As regards to fibrinogen studies have shown a positive role in predicting cardiovascular events. However, the potential prognostic role of adhesion molecules and cytokines for cardiovascular events is unclear. Thus, further studies are required to evaluate the predictive role of such molecules, as well as others under investigation in states of atherosclerosis

Novel therapies targeting vascular endothelium

Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature, may improve the long-term outcome in healthy individuals, high-risk subjects or patients with advanced atherosclerosis. Several therapeutic strategies are now available, targeting both the synthesis and oxidative inactivation of NO in human vasculature. Statins seem to be currently the most powerful category of these agents, improving endothelial function and decreasing cardiovascular risk after long-term administration. Other cardiovascular agents improving endothelial function in humans are angiotensin converting enzyme inhibitors/angiotensin receptors blockers, which increase NO bioavailability by modifying rennin-angiotensin-aldosterone system. Newer therapeutic approaches targeting endothelial dysfunction in specific disease states include insulin sensitizers, novel antioxidant compounds or combinations of classic antioxidant agents as well as substances which target endothelial nitric oxide synthase 'coupling'. In the future genetic profile may help to identify potential responders to treatments targeting specific intracellular pathways in vascular endothelium. ©2011 Nova Science Publishers, Inc. All rights reserved

Relationship between the pharmacokinetics of levosimendan and its effects on cardiovascular system.

Levosimendan, a Ca(2+) sensitizer, has emerged as an alternative option of pharmacologic inotropic support in patients with decompensated heart failure. In contrast to classic inotropes, rather than interfering with intracellular Ca(2+) levels in myocytes, levosimendan improves cardiac performance via Ca(2+) sensitization and K(+) channel-mediated peripheral vasodilatation. A two compartment pharmacokinetic model with zero-order input and first-order elimination has been found to describe best the pharmacokinetics of levosimendan. Although oral levosimendan has high bioavailability (approximately equal to 85%), in clinical practice it has been hitherto administered intravenously. Levosimendan has total clearance 175-250 mL/h/kg and most importantly a short half-life (about 1.5 hours). Therefore, this drug has a special pharmacokinetic interest: It is one of the few drugs used in cardiovascular medicine, whose prolonged action is not due to the drug itself but it is mainly due to its active metabolite OR-1896 (approximately 80 hours half life). Other metabolites with possible pharmacologic effect are N-conjugated OR-1855 (M7), N-hydroxylated OR-1855 (M8), N-hydroxylated OR-1896 (M10), O-glucuronide OR-1896 (M9) and O-sulfate (M11) of N-hydroxylated OR-1896. Initial reports on levosimendan's use in severe heart failure were positive and levosimendan has already been routinely used for the treatment of patients with decompensated heart failure, while it has been included to the European Society of Cardiology guidelines for the treatment of acute heart failure (class of recommendation IIb, level of evidence B). However, recent clinical trials have failed to demonstrate a clear benefit of levosimendan on survival, compared to other classic inotropic agents in patients requiring inotropic support. In this review article we provide a pharmacokinetic approach for the use of levosimendan in cardiovascular system by discussing its metabolism and mainly the pharmacology of its active metabolites in humans

Genetic polymorphisms of platelet glycoprotein Ia and the risk for premature myocardial infarction: effects on the release of sCD40L during the acute phase of premature myocardial infarction.

OBJECTIVES: The aim of this research was to evaluate the effect of genetic polymorphisms C807T and G1648A of platelet glycoprotein Ia (GPIa), on the risk for myocardial infarction (MI) and on the release of soluble CD40 ligand (sCD40L) during the acute phase of MI and one year after the event. BACKGROUND: C807T and G1648A polymorphisms affect the density of GPIa on platelet surface, but their effect on the risk for MI and the release of sCD40L is unknown. METHODS: The study population consisted of 219 patients with premature MI and 389 controls. One year after the event, 67 patients and 232 controls were recalled for the follow-up study. RESULTS: The risk for MI in 807TT was 2.296 (95% confidence interval [CI]: 1.187 to 4.440) p < 0.05 versus CC + CT, 2.269 (95% CI: 1.085 to 4.745) p < 0.05 versus CC, and 2.135 (95% CI: 1.080 to 4.219) p < 0.05 versus CT. During the acute phase of MI, sCD40L was higher in 807CT + TT compared with 807CC (p < 0.01), an effect persisting after one year (p < 0.01). The carriage of 807T allele was an independent predictor for sCD40L during the acute phase of MI (beta = 9.442 [standard error (SE): 2.526], p = 0.001) and in the same patients one year later (beta = 8.282 [SE: 2.044], p = 0.001). In healthy individuals, 807T allele was associated with higher sCD40L levels compared with 807CC (p < 0.05), only among those with von Willebrand factor greater than or equal to median. CONCLUSIONS: Genetic polymorphism C807T increases the risk for premature MI. 807T allele is an independent predictor for sCD40L levels during the acute phase of premature MI as well as one year after the event, while it is associated with elevated sCD40L levels in healthy subjects, only in the presence of high von Willebrand levels