A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree ...of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.
Background:
Many patients who have been suffering by C
ovid
-19 suffer of long-C
ovid
syndrome, with symptoms of fatigue and muscular weakness that characterize post-acute sequelae SARS-CoV-2 ...infection (PASC). However, there is limited knowledge about the molecular pathophysiology, and about the serum profile of these patients.
Methods:
We studied the blood serum profile of 75 selected patients, with previous confirmed C
ovid
-19, 2 months after hospital discharge, who reported new-onset fatigue, muscle weakness and/or dyspnea not present prior to the virus infection and independently from concomitant diseases and/or clinical conditions.
Results:
All patients had very high serum concentrations of ferritin and D-Dimer. 87 and 72% of patients had clinically significant low levels of hemoglobin and albumin, respectively. Seventy three percentage had elevations in erythrocyte sedimentation rate and CRP. Twenty seven percentage had elevations in LDH.
Conclusions:
The co-existence of patient symptoms along with blood markers of coagulation, protein disarrangement and inflammation suggests ongoing alterations in the metabolism, promoting an inflammatory/hypercatabolic state which maintains a vicious circles implicated in the persistence of PASC. The persistence of altered D-Dimer levels raises the possibility of long-term risks of thromboembolic disease. All these markers levels should be accurately evaluated in the long-term follow-up, with individualized consideration for prophylactic nutritional, anti-inflammatory and/or anticoagulant therapy if indicated.
Because of the inability to affect retroactively damage initiated during ischemia, attention has turned to reducing the extent of RI, the only component of the overall damage amenable to ...intervention. An alternative possibility is that we perceive as a macroscopic failure what is really a microscopic success. Because ischemia is the pre-requisite, although not the ultimate cause, of cell death, its overall duration is sort of binding, in that it can be neither too short (a situation in which the cumulative damage caused by ischemia and reperfusion may not be enough to pass the threshold of irreversibility), nor too long (which would generate an ischemic event sufficient to start and complete the cell death process, independently of reperfusion).
Dilemmas in end-stage heart failure Chen-Scarabelli, Carol; Saravolatz, Louis; Hirsh, Benjamin ...
Journal of geriatric cardiology : JGC,
2015, 2015-Jan, 20150101, Letnik:
12, Številka:
1
Journal Article
Odprti dostop
Heart failure （HF）, a complex clinical syndrome due to structural or functional disorder of the heart, is a major global health issue, with a prevalence of over 5.8 million in the USA alone, and over ...23 million worldwide. As a leading cause of hospitalizations among patients aged 65 years or older, HF is a major consumer of healthcare resources, creating a substantial strain on the healthcare system. This paper discusses the epidemiology of HF, financial impact, and multifaceted predicaments in end-stage HF care. A search was conducted on the U.S National Library of Medicine website （www.pubmed.gov） using keywords such as end-stage heart failure, palliative care, ethical dilemmas. Despite the poor prognosis of HF （worse than that for many cancers）, many HF patients, caregivers, and clinicians are unaware of the poor prognosis. In addition, the unpredictable clinical trajectory of HF complicates the planning of end-of-life care, such as palliative care and hospice, leading to underutilization of such resources. In conclusion, ethical dilemmas in end-stage HF are numerous, embroiling not only the patient, but also the caregiver, healthcare team, and society.
Chronic heart failure (CHF) is a disease with important clinical and socio-economic ramifications. Malnutrition and severe alteration of the protein components of the body (protein disarrangements), ...common conditions in CHF patients, are independent correlates of heart dysfunction, disease progression, and mortality. Autophagy, a prominent occurrence in the heart of patients with advanced CHF, is a self-digestive process that prolongs myocardial cell lifespan by the removal of cytosolic components, such as aging organelles and proteins, and recycles the constituent elements for new protein synthesis. However, in specific conditions, excessive activation of autophagy can lead to the destruction of molecules and organelles essential to cell survival, ultimately leading to organ failure and patient death. In this review, we aim to describe the experimental and clinical evidence supporting a pathophysiological role of nutrition and autophagy in the progression of CHF. The understanding of the mechanisms underlying the interplay between nutrition and autophagy may have important clinical implications by providing molecular targets for innovative therapeutic strategies in CHF patients.
Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart ...failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage.
Using transmission electron microscopy, we evaluated cells' morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1/3), inflammation (TNFα, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase).
Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival.
Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.
Chronic diseases are characterised by altered autophagy and protein metabolism disarrangement, resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia is linked to a ...worse prognosis independent of the target organ affected by the disease. Currently, the cornerstone of the therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of haematopoiesis. However, treatment strategies should incorporate the promotion of the synthesis of heme, the principal constituent of haemoglobin (Hb) and of many other fundamental enzymes for human metabolism. Heme synthesis is controlled by a complex biochemical pathway. The limiting step of heme synthesis is D-amino-levulinic acid (D-ALA), whose availability and synthesis require glycine and succinil-coenzyme A (CoA) as precursor substrates. Consequently, the treatment of anaemia should not be based only on the sufficiency of iron but, also, on the availability of all precursor molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate a standard iron infusion and a supply of essential amino acids and vitamins involved in heme synthesis. We reported preliminary data in a select population of aged anaemic patients affected by congestive heart failure (CHF) and catabolic disarrangement, who, in addition to the standard iron therapy, were treated by reinforced therapeutic schedules also providing essential animo acids (AAs) and vitamins involved in the maintenance of heme. Notably, such individualised therapy resulted in a significantly faster increase in the blood concentration of haemoglobin after 30 days of treatment when compared to the nonsupplemented standard iron therapy.
Objectives The present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)ε and PKCδ in patients with (DMPs) and without (NDMPs) diabetes ...mellitus after on-pump cardiac surgery (OPCS). The molecular mechanisms responsible for the reported worse outcomes of DMP after OPCS remain unknown. Methods Two sequential biopsy specimens were obtained from the right atrium of 27 DMPs and 22 NDMPs before and after cardiopulmonary bypass. Results Postcardioplegic induction of Ucn in NDMPs ( P < .01) was not observed in the DMPs, whose precardioplegic Ucn levels were 50% lower than those in the NDMPs ( P < .05). In the NDMPs, cardioplegic arrest increased PKCε mRNA and protein ( P < .05); overexpression of PKCδ was not seen. In contrast, DMPs showed increased PKCδ expression ( P < .01), with no change in PKCε. Apoptosis was more than twofold greater in the postcardioplegic samples from the DMPs than in those from the NDMPs. The apoptotic myocytes were Ucn negative and exhibited nuclear relocation of PKCδ. Enhanced PKCε/mitochondrial co-localization was observed in viable, Ucn-positive, myocytes. The leakage of troponin I documented in the DMPs was greater than that in the NDMPs, although the difference was not statistically significant ( P = .06). Furthermore, despite a similar incidence of perioperative acute myocardial infarction, the DMPs did not show postoperative improvement of systolic or diastolic function, although that was seen in the NDMPs ( P < .05). Conclusions Cardioplegic arrest failed to induce in DMPs myocyte overexpression of Ucn or PKCε but was associated with induction and mitochondrial relocation of PKCδ, resulting in apoptosis. Failure to overexpress Ucn in the DMPs was associated with apoptosis and cardiac dysfunction and, thus, might contribute to worse postoperative outcomes.
The Heart Rhythm Society (HRS) has been developing clinical practice documents in collaboration and partnership with other professional medical societies since 1996. The HRS formed a Scientific and ...Clinical Documents Committee (SCDC) with the sole purpose of managing the development of these documents from conception through publication. The SCDC oversees the process for developing clinical practice documents, with input and approval from the HRS Executive Committee and the Board of Trustees. As of May 2017, the HRS has produced more than 80 publications with other professional organizations. This process manual is produced to publicly and transparently declare the standards by which the HRS develops clinical practice documents, which include clinical practice guidelines, expert consensus statements, scientific statements, clinical competency statements, task force policy statements, and proceedings statements. The foundation for this process is informed by the Institute of Medicine's standards for developing trustworthy clinical practice guidelines; the new criteria from the National Guidelines Clearinghouse, effective June 2014; SCDC member discussions; and a review of guideline policies and methodologies used by other professional organizations.
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