The current studies were undertaken to explore the relationship between enhanced sympathetic nervous activity and lymphocyte subset distribution in three settings: congestive heart failure, dynamic exercise, and fl-adrenergic agonist treatment.We compared the number and subset distribution of circulating lymphocytes in 36 patients with congestive heart failure and 31 age-matched control subjects. The number of circulating lymphocytes was lower in heart failure than in control. This was due to a reduction in Tsuppressor/cytotoxic and natural killer cells without significant alteration of Thelper cells. The extent of the alteration was similar in patients with idiopathic and ischemic heart failure, but the reduction was more pronounced in patients with New York Heart Association class III-IV than in class 1-11. The plasma catecholamine elevation in heart failure was also independent of etiology but more pronounced in the more severely ill patients. We also assessed lymphocyte subsets after acute stimulation of sympathetic activity by dynamic exercise and after treatment with the ,8-adrenergic agonist terbutaline. Dynamic exercise until exhaustion increased the number of circulating lymphocytes in healthy controls and heart failure patients in a subset-selective manner. By contrast, a 7-d treatment with terbutaline caused a reduction in the circulating number of lymphocytes in some subsets that was identical to that seen in heart failure patients. We conclude that prolonged sympathetic activity reduces the number of circulating lymphocytes by a fi-adrenergic mechanism. Such alterations might be involved in the pathophysiology of heart failure and other disease states involving increased activity of the sympathetic nervous system. (J. Clin. Invest. 1990. 85:462-467.) beta receptors -lymphocytes -heart failuresympathetic nervous system

We adapted a technique for isolation of mononuclear leukocyte (MNL) subsets with immunomagnetic beads to the study of beta-adrenergic receptors. Mixed MNL cells were sequentially incubated with monoclonal antibodies specific for certain MNL subsets. Sheep antimouse antibodies coupled to magnetic beads were then added, and the desired MNL subset was pulled out with a magnet. This method yielded subsets with high purity and did not alter beta-receptor density or function. Healthy volunteers were treated for 7 days with the beta 2-selective agonist terbutaline (5 mg t.i.d.). Terbutaline treatment decreased beta-receptor number and isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) generation in natural killer cells, helper T cells, and suppressor/cytotoxic T cells but not in B cells. The decrease was greatest in suppressor/cytotoxic T cells and least in helper T cells. Thus beta-adrenergic receptor regulation by agonists appears to differ among MNL subsets.

In order to measure the energy cost of immobilization of the foot and ankle during ambulation, 14 healthy male volunteers exercised while wearing various immobilization devices. Oxygen consumption, oxygen cost, cardiac output, minute ventilation, heart rate, stroke volume, stride length, and stride frequency were determined at a steady state of exercise as the subjects walked on a treadmill at 80 m/min (equivalent to the comfortable walking speed of approximately 3 mi/h). Each subject was tested with three different types of immobilization devices: a short leg walking cast, a prefabricated lower leg orthosis, and a rigid-soled surgical shoe. The results were compared with those for the same men ambulating without an immobilization device. Ambulation with the short leg walking cast and the prefabricated lower leg orthosis required significantly more energy in comparison with control values (all p values < 0.006) in terms of oxygen cost, cardiac index, oxygen consumption, and minute ventilation. However, when the rigid-soled surgical shoe was worn, energy consumption as measured by all parameters was not significantly increased compared with control values. Comparison of the findings for the short leg walking cast and the prefabricated lower leg orthosis showed no significant differences in any parameter of energy consumption. Stride length, however, was significantly shorter in the short leg walking cast compared with all immobilizers tested.