cardiovascular-agents and Cachexia

Cachexia is defined as a complex metabolic syndrome associated with underlying illness that is characterized by the loss of body weight consisting of muscle and fat mass wasting. Sarcopenia is defined as the ageing related loss of muscle mass in health and disease that may not have an effect on body weight. As millions of patients are in cachectic or sarcopenic states, both conditions contribute to high numbers to death worldwide. A number of treatments have been proposed for cachexia and sarcopenia, but these are either in the preclinical stage or in clinical trials and hence not available to the general population. Particularly in cachexia there is a massive problem of recruiting patients for trials and also with the follow-up, due to the seriousness of the disease. This underlines the importance of well-characterized animal models. Obviously, most of the widely used cachexia and sarcopenia animal models have limitations in reproducibility of the condition and novel models are warranted in this context. The key findings of developing models in the field of cachexia and sarcopenia are that more types of the conditions have been taken into the researchers' interest. In cardiac cachexia, technical issues, which limit the preciseness and reproducibility in surgical heart failure models, have been overcome by a combination of surgery and the use of transgenic mouse models or salt sensitive rat models. Fatigue is the most pronounced symptom of cachexia and may be caused by reduced cardiac function independent of the underlying disease. Sarcopenia models often suffer from the use of young animals, due to the limited availability and very high costs of using aged animals. This review will focus on rodent models designed to mimic cachexia and sarcopenia including co-morbidities such as cancer, heart failure, as well as other diseases and conditions.

Topics: Animals; Body Composition; Cachexia; Cardiovascular Agents; Cardiovascular Physiological Phenomena; Chronic Disease; Disease Models, Animal; Exercise; Humans; Sarcopenia; Treatment Outcome

Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. We aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in the symptom generation. In the first part of the review, six key factors were revised (the heart, the lung, the skeletal muscle, the hormonal changes, the O2 delivery to the periphery, the endothelium). In this second part, the role of the excitatory reflexes and the cardiac cachexia are presented. Finally, potential therapeutic implications are discussed here. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.

Topics: Cachexia; Cardiac Resynchronization Therapy; Cardiovascular Agents; Chronic Disease; Dyspnea; Exercise Tolerance; Heart Failure; Humans; Multiple Organ Failure; Muscle Fatigue; Reflex; Treatment Outcome

Chronic cardiopulmonary disease typically induces and maintains (over)activation of several phylogenetically old adaptational and defensive mechanisms. Activation was usually needed for a limited period during acute danger or injury. In chronic disease conditions, however, those mechanisms are kept activated for longer periods. Eventually, irreversible damage is done and this contributes to impaired function and worse prognosis in a variety of chronic disease. Landmark trials in chronic heart failure have provided robust evidence for prognostic benefit for neurohormonal antagonists. Retrospective and epidemiological data for their beneficial effect in chronic obstructive pulmonary disease begin to accumulate and new fields (e.g. cancer and stroke) could be pending in the future.

Topics: Cachexia; Cardiovascular Agents; Clinical Trials as Topic; Comorbidity; Heart Failure; Humans; Inflammation; Neurotransmitter Agents; Pulmonary Disease, Chronic Obstructive; Renin-Angiotensin System; Risk Factors; Stroke

Topics: Animals; Antineoplastic Agents; Biomedical Research; Cachexia; Cardiovascular Agents; Cardiovascular Diseases; Drug Design; Genetic Therapy; Humans; Mice; MicroRNAs; Muscle, Skeletal; Neoplasms; Proteasome Endopeptidase Complex; Telomere; Ubiquitin; Ubiquitination

Topics: Cachexia; Cardiovascular Agents; Chronic Disease; Heart Failure; Humans; Male; Testosterone; Treatment Outcome

Cardiac cachexia, a loss of lean body mass caused by heart disease, often accompanies congestive heart failure (CHF). Blocking myostatin, which is a protein that inhibits muscle growth, appears to greatly enhance muscle size and strength in rodent models and human clinical trials. The objective of this study was to evaluate a dog-specific myostatin antagonist (CAP-031) in a pilot study to test its safety and efficacy in dogs with CHF and cardiac cachexia.. Dogs with CHF and cardiac cachexia.. Eligible dogs received four weekly subcutaneous injections of CAP-031. Endpoints were body weight, body condition score (BCS, on a 1-9 scale), muscle condition score (MCS, on a five-point scale, where 0 = no muscle loss and 4 = severe muscle loss), appetite, and a quality of life (QOL) score.. Seven dogs with CHF and moderate-to-severe cachexia were enrolled in the study. For the six dogs that completed the study, the median age was 8.8 years (range 6.4-10.6). At baseline, the median body weight was 27.0 kg (range 17.3-62.0), the median BCS was 4 (2-5), and median MCS was 3 (3-4). There were no significant changes in body weight, BCS, appetite, or QOL score. The change in MCS (from a median of 3 at baseline to a median of 2.5 at week 4) was not statistically significant (p = 0.06).. The myostatin antagonist appeared to be well tolerated in most dogs. Earlier identification of cachexia is important, and randomized, controlled trials of myostatin antagonists or other drugs to treat cardiac cachexia are needed.

Topics: Activin Receptors, Type II; Animals; Cachexia; Cardiovascular Agents; Dog Diseases; Dogs; Female; Heart Diseases; Male; Myostatin; Pilot Projects

Topics: Aprotinin; Cachexia; Cardiovascular Agents; Chloramphenicol; Drug Therapy; Muscle Relaxants, Central; Pancreas; Pancreatitis; Penicillins; Procaine; Toxicology; Trypsin Inhibitors