Pathophysiology of peripheral muscle wasting in cardiac cachexia.
ABSTRACT Many different mechanisms have been proposed to explain muscle wasting in patients with heart failure; however, the pathogenesis remains largely obscure. This manuscript looks at current developments concerning the pathophysiology of skeletal muscle wasting in cardiac cachexia.
Many studies have shown that malnutrition, malabsorption, metabolic dysfunction, anabolic/catabolic imbalance, inflammatory and neurohormonal activation, and cell death play an important role in the pathogenesis of wasting in cardiac cachexia. However, the aetiology of the muscle changes is not entirely clear. In biopsies of skeletal muscles from animals with cardiac cachexia increased rates of protein degradation have been observed, with increased activity of the ubiquitin-proteasome proteolytic pathway. Skeletal muscle apoptosis may also play a role in muscle atrophy and wasting and can be partly prevented by neurohormonal inhibition, but it has recently been reported that in cachectic patients with chronic heart failure apoptosis is not the main pathway of cell death and muscle loss.
Many hypotheses have been used to explain the pathogenesis of muscle wasting in cardiac cachexia. Cardiac cachexia is a multifactorial disorder, and the targeting of different pathways will be necessary for effective treatment. The immune and neurohormonal abnormalities present in chronic heart failure may play a significant role in the pathogenesis of the wasting process. It has been suggested that common pathogenetic mechanisms underlie the loss of muscle mass in different cachectic states. More studies are needed to show whether there is a common pathway in cardiac cachexia and the other cachectic states.
African journal of pharmacy and pharmacology 01/2012; 6(4):241-247. DOI:10.5897/AJPP11.615 · 0.84 Impact Factor
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ABSTRACT: Background Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (CHF). Objectives We hypothesized that similar patterns of cardiovascular perturbations are present in CRC and CHF. Methods We prospectively studied 50 patients with CRC, 51 patients with CHF, and 51 control subjects. The CRC group was divided into 2 subgroups: patients who underwent chemotherapy (n = 26) and chemotherapy-naive patients (n = 24). We assessed exercise capacity (spiroergometry), cardiac function (echocardiography), heart rate variability (Holter electrocardiography), body composition (dual-energy x-ray absorptiometry), and blood parameters. Results Compared with the control arm, the left ventricular ejection fraction (CRC group 59.4%; control group 62.5%) and exercise performance as assessed by peak oxygen consumption (peak VO2) (CRC group 21.8 ml/kg/min; control group 28.0 ml/kg/min) were significantly reduced in CRC patients (both p < 0.02). Markers of heart rate variability were markedly impaired in CRC patients compared with control subjects (all p < 0.008). Compared with the control group, the CRC group also showed reduced lean mass in the legs and higher levels of the endothelium-derived C-terminal-pro-endothelin-1 (both p < 0.02). Major determinants of cardiovascular function were impaired in chemotherapy-treated patients and in the chemotherapy-naive patients, particularly with regard to exercise capacity, left ventricular ejection fraction, lean mass, and heart rate variability (all p < 0.05 vs. control subjects). Conclusions Some aspects of cardiovascular function are impaired in patients with CRC. More importantly, our findings were evident independently of whether patients were undergoing chemotherapy.Journal of the American College of Cardiology 09/2014; 64(13):1310–1319. DOI:10.1016/j.jacc.2014.07.948 · 15.34 Impact Factor
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ABSTRACT: Objective T o investigate the prevalence, profi le and predictors of severe malnutrition in children with congenital heart defects (CHDs). Design Case–control, observational study. Setting Tertiary teaching hospital in Lagos, Nigeria (March 2006 to March 2008). Participants Children aged 3–192 months with uncorrected symptomatic CHD and healthy controls, frequency matched for age and sex. Main outcome measures Prevalence of malnutrition based on WHO/National Center for Health Statistics/ Centers for Disease Control and Prevention z score ≤−2; weight for age, weight for height/length and height for age; proportions of underweight, wasting and stunting in cases and controls, and in acyanotic and cyanotic CHD; and predictors of malnutrition using multivariate logistic analysis. Results 90.4% of cases and 21.1% of controls had malnutrition (p=0.0001), and 61.2% and 2.6%, respectively, had severe malnutrition (p=0.0001). Wasting, stunting and underweight were identifi ed in 41.1%, 28.8% and 20.5%, and 2.6%, 3.9% and 14.5% of cases and controls, respectively. Wasting was signifi cantly higher (58.3%) in acyanotic CHD (p=0.0001), and stunting (68.0%) in cyanotic CHD (p=0.0001). Age at weaning was signifi cantly lower in cases than controls (3.24±0.88 and 7.04±3.04 months, respectively; p=0.0001) and in acyanotic than cyanotic CHD (2.14±0.33 and 5.33±1.22 months, respectively; p=0.004). Predictors of malnutrition in CHD were anaemia, moderate to severe congestive heart failure (CHF) , poor dietary intake of fat and prolonged unoperated disease. Conclusion Severe malnutrition in association with anaemia and moderate to severe CHF is highly prevalent in CHD preoperatively in these children. Early weaning may be a marker of feeding diffi culties in heart failure.Archives of Disease in Childhood 01/2011; 96(4):354-360. · 2.91 Impact Factor