Effects of beta-adrenergic blockade on the cardiac response to maximal and submaximal exercise in man.

Many of the changes in cardiac performance that take place during exercise resemble those that result from stimulation of the sympathetic nervous pathways to the heart. It has therefore been thought likely that an increase in sympathetic nervous activity occurs during exercise and is important in the mediation of the associated cardiac response. To test this hypothesis a variety of experimental approaches have been employed. Several investigators have studied the manner in which surgical denervation of the heart in the dog affects its performance during exercise (1-7), and others have examined the effects of a variety of antiadrenergic drugs on the response to exercise in man (8-12). The results have been conflicting, with some groups ascribing little, if any, importance to the sympathetic system in the over-all performance of the heart (1, 2, 4, 6, 7, 9-11), whereas others believe that the sympathetic nerves do play a major role (3, 5, 8). The interpretation of these earlier studies is complicated. In several of the experiments utilizing surgical denervation, section of the sympathetic nerves was not confined to those innervating the heart (1-3, 5). In others, the parasympathetic innervation of the heart was also interrupted (4-7), and some experiments were performed under general anesthesia (3). Furthermore, it is quite unknown to what extent conclusions based on studies in the dog can be applied to exercising man. In previous investigations on human subjects in which guanethidine or syrosingopine was administered, the sympathetic blockade involved not only the heart but the venous and arterial beds as well (8, 12). The recent development of spe-