BACKGROUND Many secondary abnormalities in chronic heart failure (CHF) may reflect physical deconditioning. There has been no prospective, controlled study of the effects of physical training on hemodynamics and autonomic function in CHF. METHODS AND RESULTS In a controlled crossover trial of 8 weeks of exercise training, 17 men with stable moderate to severe CHF (age, 61.8 +/- 1.5 years; left ventricular ejection fraction, 19.6 +/- 2.3%), increased exercise tolerance (13.9 +/- 1.0 to 16.5 +/- 1.0 minutes, p less than 0.001), and peak oxygen uptake (13.2 +/- 0.9 to 15.6 +/- 1.0 ml/kg/min, p less than 0.01) significantly compared with controls. Training increased cardiac output at submaximal (5.9-6.7 l/min, p less than 0.05) and peak exercise (6.3-7.1 l/min, p less than 0.05), with a significant reduction in systemic vascular resistance. Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production (-10.5%, p less than 0.05). Sympathovagal balance was altered by physical training when assessed by three methods: 1) RR variability (+19.2%, p less than 0.05); 2) autoregressive power spectral analysis of the resting ECG divided into low-frequency (-21.2%, p less than 0.01) and high-frequency (+51.3%, p less than 0.05) components; and 3) whole-body radiolabeled norepinephrine spillover (-16%, p less than 0.05). These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training. CONCLUSIONS Carefully selected patients with moderate to severe CHF can achieve significant, worthwhile improvements with exercise training. Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF, including abnormalities in autonomic balance.

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One of the well recognized stimuli for central pontine myelinosis (CPM) is the rapid correction of chronic hyponatraemia. Conventionally this has been perceived to lead to pontine glial cell swelling through osmosis and eventually to cell death. However, although a purely osmotic argument has been central to any patho‐physiological understanding of CPM, there are deficiencies in this approach that do not account for why certain individuals develop CPM with relatively mild osmotic insults. Here we review the varying aetiologies of CPM and propose a novel hypothesis for CPM causation by suggesting that individuals predisposed to CPM have inadequate energy provision as well as other factors that result in a pro‐apoptotic drive, which renders them susceptible to brain injury from diverse causes. In CPM, the precipitant of brain injury appears to be osmotic stress. Furthermore, this model suggests a number of therapeutic interventions that may prevent or at least mitigate the consequences of CPM.