EFFECTS OF NERVE STIMULATION AND HORMONES ON THE HEART 



547 



ventricular response like the normal exercise responses 

 are apparently closely related to the sympathetic 

 vasodilator system which Uvnas (50), Folkow (10) 

 and their collaborators have described. This system 

 is beliesed to convey impulses from higher centers in 

 the nervous system to induce vasodilation in skeletal 

 muscle at the onset of exercise. The distribution of 

 blood flow through different vascular beds has been 

 registered continuously and simultaneously by ultra- 

 sonic flowmeter. During spontaneous activity by 

 healthy dogs the splanchnic and renal flows are 

 altered very little, but the blood flow to the hind- 

 quarters is promptly increased at the onset of e.xercise. 

 The same localized diencephalic stimulation which 

 caused profound cardiac responses also reproduced 

 quite closely the changes in peripheral flow distribu- 

 tion which had been observed during exercise on the 

 same day. The increased flow through the terminal 

 aorta during diencephalic stimulation apparently 

 results from activation of the sympathetic vasodilator 

 system for the skelectal muscles. 



Clearly, there are anatomical pathways within 

 the nervous system that carry impulses which will 

 trigger a complete cardiovascular-respiratory response 

 to exercise without any influence from peripheral 

 control mechanisms. This demonstration does not 

 prove that this is the manner in which exercise 

 responses are normally initiated, but clearly shows 

 the possibility of this mechanism. The diencephalon 

 is probably a crossroads for nerve impulses coming 

 from many portions of the cerebral cortex, so that 

 the neural mechanisms that initiate movements of 

 the skeletal muscle can theoretically initiate the 

 appropriate cardiovascular-respiratory response at 

 the .same time. The cardiac contribution to this 

 response consists primarily of cardioacceleration and 

 increased contractility of the sort illustrated in figures 

 I and 2. Note that the more rapid rate of tension 

 development and the faster ejection velocity are 

 consistent with a shorter systole without a reduction 

 in stroke volume. The shortened systolic interval 

 spares the time for diastolic filling and contributes to 

 the effectiveness of the tachycardia in augmenting 

 the cardiac output. On the other hand, there is no 

 obvious role of the Frank-.Starling mechanism in the 

 responses to exertion and diencephalic stimulation. 



The cardiovascular research of the future will 

 undoubtedly focus heavily on the interactions within 

 the central nervous system which lead to integrated 

 responses. On the basis of past problems progress 

 will be accelerated if a clear distinction is made 



between the central or integrated control mechanisms 

 and the peripheral or local mechanisms. 



INTEGRATED AND LOCAL MECHANISMS OF 

 CARDIOVASCULAR CONTROL 



Overt behavioral changes in unanesthetized animals 

 can be induced by electrical stimulation of many 

 different portions of the brain, including the motor 

 cortex, cingulate gyrus, prefrontal area and amygdala. 

 In general, stimulation in these regions also influences 

 the cardiovascular system (37). Neuronal pathways 

 from these areas funnel through the diencephalon, 

 through the medulla, and terminate on the pre- 

 ganglionic sympathetic cell bodies in the intermedio- 

 lateral cell columns of the thoracic cord. These chains 

 of ner\e fibers may or may not be interrupted by 

 synapses, even in the medullary region, although 

 collateral fibers are given off en route. These path- 

 ways form a basis for generalized cardiovascular 

 responses, initiated from the central nervous system 

 and integrated into patterns affecting widely distant 

 portions of the autonomic nervous system. The 

 extent of the cardiovascular response may depend 

 upon previous experience (i.e., conditioning). This 

 fact is evidenced by the manner in which the over- 

 shoot in the responses observed during the first tread- 

 mill exercise often diminishes rapidly so that, after 

 a few trials, the variables promptly reach a plateau 

 which persists without adjustment during the re- 

 mainder of the exercise (39). Although it is possible 

 that nervous impulses from receptors widelv dis- 

 tributed through the peripheral vascular system 

 modulate the intensity of the cardiovascular response, 

 such a mechanism has not been definitively demon- 

 strated. These integrated responses originating in the 

 central nervous system bear little resemblance to 

 those depicted in the concepts of peripheral vascular 

 control derived from experiments on anesthetized 

 animals and based on peripheral mechanisms. Periph- 

 eral or local mechanisms become manifest when the 

 normal neural controls are eliminated. For example, 

 surgical removal of the sympathetic nervous system 

 is followed by rather severe dislocation of tlie periph- 

 eral vascular activity for a brief period, but after a 

 few weeks the peripheral vessels regain a measure of 

 control which permits quite normal activity and 

 rapid adaptation. This observation does not mean 

 that the sympathetic nervous system is not important 

 in normal peripheral vascular control. It signifies 

 instead that an additional mechanism in the periphery 



