Post-conditioning (Post-C) induced cardioprotection involves activation of guanylyl-cyclase. In the ischemic preconditioning scenario, the downstream targets of cGMP include mitochondrial ATP-sensitive K(+) (mK(ATP)) channels and protein kinase C (PKC), which involve reactive oxygen species (ROS) production. This study tests the hypothesis that mK(ATP), PKC and ROS are also involved in the Post-C protection. Isolated rat hearts underwent 30 min global ischemia (I) and 120 min reperfusion (R) with or without Post-C (i.e., 5 cycles of 10 s R/I immediately after the 30 min ischemia). In 6 groups (3 with and 3 without Post-C) either mK(ATP) channel blocker, 5- hydroxydecanoate (5-HD), or PKC inhibitor, chelerythrine (CHE) or ROS scavenger, N-acetyl-cysteine (NAC), were given during the entire reperfusion (120 min). In other 6 groups (3 with and 3 without Post-C), 5-HD, CHE or NAC were infused for 117 min only starting after 3 min of reperfusion not to interfere with the early effects of Post-C and/or reperfusion. In an additional group NAC was given during Post-C maneuvers (i.e., 3 min only). Myocardial damage was evaluated using nitro-blue tetrazolium staining and lactate dehydrogenase (LDH) release. Post-C attenuated myocardial infarct size (21 +/- 3% vs. 64 +/- 5% in control; p < 0.01). Such an effect was abolished by 5-HD or CHE given during either the 120 or 117 min of reperfusion as well as by NAC given during the 120 min or the initial 3 min of reperfusion. However, delayed NAC (i.e., 117 min infusion) did not alter the protective effect of Post- C (infarct size 32 +/- 5%; p < 0.01 vs. control, NS vs. Post-C). CHE, 5-HD or NAC given in the absence of Post-C did not alter the effects of I/R. Similar results were obtained in terms of LDH release. Our data show that Post-C induced protection involves an early redox-sensitive mechanism as well as a persistent activation of mK(ATP) and PKC, suggesting that the mK(ATP)/ROS/PKC pathway is involved in post-conditioning.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells following binding with the cell surface ACE2 receptors, thereby leading to coronavirus disease 2019 (COVID-19). SARS-CoV-2 causes viral pneumonia with additional extrapulmonary manifestations and major complications, including acute myocardial injury, arrhythmia, and shock mainly in elderly patients. Furthermore, patients with existing cardiovascular comorbidities, such as hypertension and coronary heart disease, have a worse clinical outcome following contraction of the viral illness. A striking feature of COVID-19 pandemics is the high incidence of fatalities in advanced aged patients: this might be due to the prevalence of frailty and cardiovascular disease increase with age due to endothelial dysfunction and loss of endogenous cardioprotective mechanisms. Although experimental evidence on this topic is still at its infancy, the aim of this position paper is to hypothesize and discuss more suggestive cellular and molecular mechanisms whereby SARS-CoV-2 may lead to detrimental consequences to the cardiovascular system. We will focus on aging, cytokine storm, NLRP3/inflammasome, hypoxemia, and air pollution, which is an emerging cardiovascular risk factor associated with rapid urbanization and globalization. We will finally discuss the impact of clinically available CV drugs on the clinical course of COVID-19 patients. Understanding the role played by SARS-CoV2

Reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction (AMI)�� However reperfusion is responsible for additional myocardial damage, which likely involves opening of the mitochondrial permeability transition pore (mPTP)�� In reperfusion injury, mitochondrial damage is a determining factor in causing loss of cardiomyocyte function and viability�� Major mechanisms of mitochondrial dysfunction include the long lasting opening of mPTPs and the oxidative stress resulting from formation of reactive oxygen species (ROS)�� Several signaling cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning, obtained with brief intermittent ischemia or with pharmacological agents�� These pathways converge on a common target, the mitochondria, to preserve their function after ischemia/reperfusion�� The present review discusses the role of mitochondria in cardioprotection, especially the involvement of adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP�� Ischemic postconditioning has emerged as a new way to target the mitochondria, and to drastically reduce lethal reperfusion injury�� Several clinical studies using ischemic postconditioning during angioplasty now support its protective effects, and an interesting alternative is pharmacological postconditioning�� In fact ischemic postconditioning and the mPTP desensitizer, cyclosporine A, have been shown to induce comparable protection in AMI patients��

Intermittent targeting of specific cellular sites (i.e. BK B2 receptors and mK(ATP) channels) during early reperfusion triggers PostC protection via ROS signaling. Since neither intermittent oxygenation nor exogenous ROS generators can trigger protection, it is likely that intermittent autacoid accumulation and ROS compartmentalization may play a pivotal role in PostC-triggering.

This article discusses the theory and practice of health and education, beginning with the notion of the hegemony (in health education practice) of strategies linked to the notion that to grasp established knowledge always leads to the acquisition of new behaviors and practices. Five different axioms have oriented education and health practices, either juxtaposed or at different moments: (1) the notion of overcoming the determination of knowledge over practices; (2) the determination of representations over practices; (3) the analysis of representations within the traditional framework of right and wrong; (4) reciprocity between representations and practices; and (5) the importance of considering practices amenable to re-elaboration through representations, thus situating experience in understanding subjects' illness processes, as well as the way subjects culturally construct illness. The article highlights the need for a link between social representations and illness-as-experience in health education practices.

We aimed to assess the role of the nitric oxide (NO)-cGMP pathway in cardioprotection by brief intermittent ischemias at the onset of reperfusion (i.e., post-conditioning (Post-con)). We also evaluated the role of coronary flow and pressure in Post-con. Rat isolated hearts perfused at constant- flow or -pressure underwent 30 min global ischemia and 120 min reperfusion. Post-con obtained with brief ischemias of different duration (modified, MPost-con) was compared with Post-con obtained with ischemias of identical duration (classical, C-Post-con) and with ischemic preconditioning (IP). Infarct size was evaluated using nitro-blue tetrazolium staining and lactate dehydrogenase (LDH) release. In the groups, NO synthase (NOS) or guanylyl-cyclase (GC) was inhibited with LNAME and ODQ, respectively. In the subgroups, the enzyme immunoassay technique was used to quantify cGMP release. In the constant-flow model, M-Post-con and C-Post-con were equally effective, but more effective than IP in reducing infarct size. The cardioprotection by M-Post-con was only blunted by the NOS-inhibitor, but was abolished by the GC-antagonist. Post-ischemic cGMP release was enhanced by MPost-con. In the constant-pressure model IP, M-Post-con and C-Post-con were equally effective in reducing infarct size. Post-con protocols were more effective in the constant-flow than in the constant-pressure model. In all groups, LDH release during reperfusion was proportional to infarct size. In conclusion, Post-con depends upon GC activation, which can be achieved by NOS-dependent and NOS-independent pathways. The benefits of M- and CPost-con are similar. However, protection by Post-con is greater in the constant-flow than in the constant-pressure model.

Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. CTX can occur within a few days or many years after treatment. Type I CTX is associated with irreversible cardiac cell injury, and it is typically caused by anthracyclines and traditional chemotherapeutics. Type II CTX is generally caused by novel biologics and more targeted drugs, and it is associated with reversible myocardial dysfunction. Therefore, patients undergoing anti-cancer treatments should be closely monitored, and patients at risk of CTX should be identified before beginning treatment to reduce CTX-related morbidity. Genetic profiling of clinical risk factors and an integrated approach using molecular, imaging, and clinical data may allow the recognition of patients who are at a high risk of developing chemotherapy-related CTX, and it may suggest methodologies to limit damage in a wider range of patients. The involvement of redox mechanisms in cancer biology and anticancer treatments is a very active field of research. Further investigations will be necessary to uncover the hallmarks of cancer from a redox perspective and to develop more efficacious antineoplastic therapies that also spare the cardiovascular system. Antioxid. Redox Signal. 00, 000-000.