The Role of Glucagon-like Peptide-1 in the Pathophysiology of Heart Failure: A Special Focus.

Glucagon-like peptide-1 (GLP-1) within the brain is a potent regulator of food intake and most studies have investigated the anorexic effects of central GLP-1. A range of brain regions have now been found to be involved in GLP-1 mediated anorexia, including some which are not traditionally associated with appetite regulation. However, a change in food intake can be indicative of not only reduced energy demand, but also changes in the organism’s motivation to eat following stressful stimuli. In fact, acute stress is well-known to reduce food intake. Recently, more research has focused on the role of GLP-1 in stress and the central GLP-1 system has been found to be activated in response to stressful stimuli. The source of GLP-1 within the brain, the preproglucagon (PPG) neurons, are ideally situated in the brainstem to receive and relay signals of stress and our recent data on the projection pattern of the PPG neurons to the spinal cord suggest a potential strong link with the sympathetic nervous system. We review here the role of central GLP-1 in the regulation of stress responses and discuss the potential involvement of the endogenous source of GLP-1 within the brain, the PPG neurons.

Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions. However, the patho-genesis of hypoglycaemic counterregulation is still unclear. Glucagon-like peptide-1 (GLP-1) and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus (T1DM). The role of GLP-1 in counterregulatory dys-function during hypoglycaemia in patients with T1DM has not been reported. To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice. T1DM was induced in C57BL/6J mice using streptozotocin, followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia (DH5). Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon (GCG) secretion. The GLP-1 receptor agonist GLP-1(7-36) or the antagonist exendin (9-39) were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice. The expression levels of intestinal GLP-1 and its receptor (GLP-1R) were significantly increased in DH5 mice. Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex, leading to dysfunction of adrenal counterregulation during hypoglycaemia. DH5 mice showed increased pancreatic δ-cell mass, cAMP levels in δ cells, and plasma somatostatin concentrations, while cAMP levels in pancreatic α cells and plasma GCG levels decreased. Furthermore, GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group. Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway. Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia, leading to reduced appetite and compromised secretion of adrenaline, noradrenaline, and GCG during hypo-glycaemia.

Pathophysiology of heart failure has been considered to be a damaged state of systolic function of the heart followed by a state of low cardiac output that is, systolic heart failure. Even if systolic function is preserved, left ventricular filling in diastole can be impeded and resulted in elevation of filling pressure and symptoms of heart failure. This kind of heart failure is called diastolic heart failure. Nowadays, diastolic heart failure is referred to as heart failure with preserved ejection fraction (HFpEF), whereas systolic heart failure is referred to as heart failure with reduced ejection fraction (HFrEF). In this paper, the similarities and differences between the pathogenesis and pathophysiology of diastolic and systolic heart failure were reviewed. Although diastolic heart failure is a common condition of heart failure worldwide, its pathophysiology has not been sufficiently elucidated. This is thought to be the most significant reason for a lack of established treatment methods for diastolic heart failure. We hope to proceed with future studies on this topic.

Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure

In recent years, an interesting shift in our understanding of chronic heart failure (CHF) pathophysiology may be observed. Beyond the traditional concepts of hemodynamic failure and neuroendocrine activation, it is increasingly appreciated that CHF is a much more complex and truly systemic disease including the peripheral organs and whole body regulatory processes as well. Novel concepts such as the systemic inflammatory immune activation and the skeletal muscle hypothesis have emerged.1 These concepts recognize the significant contribution of peripheral changes to symptomatic status, disease progression, and outcome in CHF. Article see p 185 A further novel facet in heart failure pathophysiology has emerged recently because impaired regulation of systemic metabolic balance is increasingly in the focus of clinical research. The emerging picture suggests a complex but characteristic pattern of metabolic pathways that are imbalanced, attenuated, or abnormally activated. Hormonal imbalances have been previously observed as common features in CHF, such as insulin resistance2 and growth hormone resistance3 that contribute to both morbidity and mortality of patients. The metabolic interaction of neuroendocrine activation and immune activation such as from cytokines and oxygen radical accumulation add to the complexity of these interrelated processes. In general, the findings repeat, again, the classical concept of short-term beneficial adaptive responses on acute injury or disease may eventually turn into harmful maladaptive signals on prolonged and chronic activation. The overall clinical effects that may be observed from impaired energy metabolic efficacy contribute to impaired exercise capacity, muscle fatigue, and early exhaustion—key symptoms in heart …

The therapeutic potential of GLP-1 analogues for stress-related eating and role of GLP-1 in stress, emotion and mood: a review

MECHANICAL support of the cardiovascular system is an important therapeutic modality for a growing number of patients with congestive heart failure.Certain patients with refractory end-stage failure who will likely succumb to their disease before a potential heart transplant may be effectively "bridged to transplant" by a left ventricular assist device (LVAD).Three such devices are currently approved by the US Food and Drug Administration for this indication.Several ongoing multicenter clinical trials are also evaluating LVAD therapy as an alternative to transplantation ("destination therapy").Preliminary data from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure Trial indicate that an implantable LVAD prolongs survival and enhances quality of life in patients with end-stage heart failure. 1 The efficacy of destination therapy will undoubtedly lead to an expansion in the number of LVADsupported patients in future years.Some of these patients will require operations for noncardiac, non-LVAD problems.Anesthesiologists should therefore be familiar with the unique considerations related to these patients and their devices.Accordingly, this review presents important features of the commonly used devices, describes the effects of LVAD therapy on the pathophysiology of heart failure, and discusses the major perioperative considerations for patients who come to the operating room with an implanted LVAD.The discussion focuses on the patient with a chronically implanted device, not on the implantation procedure itself, which involves a different set of physiologic challenges and anesthetic considerations.

Epidemiology, pathophysiology, and prevention of heart failure in people with HIV

Changing strategies in the management of heart failure

Heart failure (HF) is a critical complication in both type 1 (T1D) and type 2 diabetes (T2D) and people with diabetes are at higher risk of developing HF than those without diabetes. The pathophysiology of HF in diabetes often involves diabetic cardiomyopathy, driven by insulin deficiency, insulin resistance (IR), inflammation, and myocardial fibrosis; however, though there are similarities in HF in T1D and T2D, there are also key differences in epidemiology, pathophysiology, treatment, and clinical outcomes. In this review article we will discuss the burden, pathophysiology, and outcomes of HF in diabetes, focusing on differences between T1D and T2D, and the relative unmet need for patients with T1D and HF.

Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy

Oxidative stress, defined as an excess production of reactive oxygen species (ROS) relative to antioxidant defense, has been shown to play an important role in the pathophysiology of cardiac remodeling and heart failure (HF). It induces subtle changes in intracellular pathways, redox signaling, at lower levels, but causes cellular dysfunction and damage at higher levels. ROS are derived from several intracellular sources, including mitochondria, NAD(P)H oxidase, xanthine oxidase, and uncoupled nitric oxide synthase. The production of ROS is increased within the mitochondria from failing hearts, whereas normal antioxidant enzyme activities are preserved. Chronic increases in ROS production in the mitochondria lead to a catastrophic cycle of mitochondrial DNA (mtDNA) damage as well as functional decline, further ROS generation, and cellular injury. ROS directly impair contractile function by modifying proteins central to excitation-contraction coupling. Moreover, ROS activate a broad variety of hypertrophy signaling kinases and transcription factors and mediate apoptosis. They also stimulate cardiac fibroblast proliferation and activate the matrix metalloproteinases, leading to the extracellular matrix remodeling. These cellular events are involved in the development and progression of maladaptive myocardial remodeling and failure. Oxidative stress is also involved in the skeletal muscle dysfunction, which may be associated with exercise intolerance and insulin resistance in HF. Therefore, oxidative stress is involved in the pathophysiology of HF in the heart as well as in the skeletal muscle. A better understanding of these mechanisms may enable the development of novel and effective therapeutic strategies against HF.

Objective: to establish, through a narrative-critical review, the pathophysiology, prevalence, diagnosis and therapeutic management of heart failure (HF). It also demonstrated the association of HF with cardiovascular biomarkers, such as interleukin 1β and its receptors. Methods: literature review based on scientific articles from the PubMed, LILACS and SciELO databases. Descriptors based on studies published in the years 2014 to 2023 and adherence to the theme "heart failure" were used. Studies without complete publications and without free availability on the data platform were excluded. Results: 204, 22 and 6 articles were obtained from the PubMed, LILACS and SciELO databases, respectively. Of these, 18, 2 and 2 articles from PubMed, LILACS and SciELO, respectively, stood out after evaluation and use of exclusion criteria. Finally, 17 articles and a textbook make up this study. Conclusion: HF is a syndromic pathology caused by a series of different etiological diagnoses. Patients with HF have several compensatory mechanisms, in addition to occasional cardiac remodeling and repair guided by inflammatory mediators. In this disease, biomarkers are very useful, being widely studied in recent years. An important highlight is the 1β interleukins, which are useful in the diagnosis and therapeutic management of HF.

A variety of clinical and experimental investigations have suggested that tumor necrosis factor alpha (TNF-alpha) may play a role in the pathophysiology of heart failure. Serum levels of TNF-alpha are elevated in patients with heart failure, and both cardiac and infiltrating cells of the myocardium can produce this proinflammatory cytokine. Both cardiac myocytes and nonmyocytes also express receptors for TNF-alpha, and experimental studies on isolated cells, muscles, and transgenic models demonstrate the ability of TNF-alpha to recapitulate functional and biochemical alterations resembling that observed in human congestive heart failure. The intracellular pathways affected by TNF-alpha include production of ceramide and an alteration in calcium metabolism. Recent studies in both animal models and clinical investigations suggest that anti-TNF-alpha therapies may limit the pathophysiologic consequences of congestive heart failure.

Literature Review: Pathophysiology of Heart Failure with Preserved Ejection Fraction