EFFECTS OF NERVE STIMULATION AND HORMONES ON THE HEART 



545 



£ (a)STROKE volume (MAN) 



(a)STflOKE VOLUME tOOG) 



^ fl-V OXYGEN DIFFERENCE 



Oxygen Consumption 



(O) HEART RATE (MAN) 



0«ygen Consumption 



FIG. 7. A: in normal human subjects, the stroke volume 

 displayed little evidence of a progressive increase with increasing 

 severity of exercise as indicated by the oxygen consumption. 

 B: judged from available evidence, the stroke volume in the 

 recumbent dog is approximately maximal. The stroke 

 volume is greatly diminished on standing and increases slightly 

 or not at all over a wide range of exertion. It is postulated 

 that stroke volume may increase as the heart rate levels off at 

 the highest levels of exertion, as in human subjects. C: the 

 oxygen extraction (arteriovenous O; difference) increases 

 progressively over a wide range of exertion. D: in contrast, the 

 heart rate accelerates up to a level of about 1 80 beats per minute 

 and then levels off. The stroke volume is lower during standing 

 control than during the recumbent control periods. .\t very low 

 levels of exertion, the stroke volume approximates the recum- 

 bent control values and then increases very little until maximal 

 exertion is attained. 



set at a 10 to 14'^x grade) (26). Such exertion could 

 be sustained for only 2V2 min, so the subjects were 

 obviously not in the steady state. In fact, tliey were 

 accumulating an oxygen debt at a prodigious rate. 

 Stroke volume increases during exertion under 

 certain conditions. In dogs, stroke volume is aug- 

 mented during exercise when the heart rate is con- 

 trolled from an external source (52). Generally 

 speaking, any circumstance which will interfere with 

 or reduce the extent of the cardioacceleration will 

 be accompanied by an increase in stroke volume. 

 Subjects exhibiting increased stroke volume during 

 exercise for such a reason include: a) trained athletes, 

 b) patients with chronic volume loads on the heart 

 (4), c) persons with tachycardia during the control 

 period, and d) patients with relatively fixed heart 

 rates as a result of such states as paroxysmal tachy- 

 cardia and complete atrioventricular block. However, 

 the fact remains that cardioacceleration and increased 

 oxygen extraction represent the principal mechanisms 

 for increased delivery of oxygen during the types of 

 exertion encountered by average normal humans and 

 dogs in their everyday lives. A progressive increase in 

 stroke volume in relation to the severitv of exertion is 



not the typical response to moderate exercise by 

 dogs or average normal persons (12, 32, 33, 35, 36, 



39, 46, 47). 



NEUR.\L MECHANISMS OF C.'>iRDI.'>iC CONTROL 



Once the techniques had been developed to describe 

 the cardiac responses in healthy dogs during spon- 

 taneous activity, the door was open for a comparative 

 study to determine whether the exercise response 

 could be simulated experimentally in the same dog 

 on the same day (36). First, the effects of increasing 

 "venous return" by intravenous infusions, compression 

 of the abdomen, and passive tilting were compared 

 with the response to exercise. The changes in ventric- 

 ular performance elicited by these maneuvers bore 

 no obvious relation to the pattern during treadmill 

 exercise at 3 mph on a 5 per cent grade. Similarly, 

 reduced peripheral resistance brought about by an 

 experimental arteriovenous shunt failed to reproduce 

 the exercise response. Since contractility can be 

 increased by catecholamines, epinephrine and 

 norepinephrine were infused at rates based on the 

 estimated secretion rates of the adrenal medulla 

 during exercise. Under these conditions, the heart 

 rate slowed and the other changes did not resemble 

 the exercise reponse. Thus, it seemed unlikely that 

 circulating epinephrine plays a dominant role in the 

 response to normal exercise. 



Previous experiments had indicated that the sympa- 

 thetic nerves to the heart in intact dogs have a power- 

 ful influence on ventricular performance similar to 

 that evidenced during exercise (i). As a next step, 

 the central nervous system was explored to discover 

 whether the patterns of cardiovascular function 

 generally observed dinnng exercise could be elicited 

 by electrical stimulation of discrete areas. It was 

 soon learned that stimulation in very small areas in 

 the region of the H2 field of Forel and in the peri- 

 ventricular gray produced changes in left ventricular 

 performance which were very similar to the exercise 

 responses in the same dog on the same day (fig. 8). 

 Differences in the diastolic ventricular pressure were 

 consistently observed; otherwise, the patterns could 

 be reproduced with fidelity. 



These areas can be consistently and rcproducibly 

 activated by weak stimuli in the same dog and in 

 different dogs, under chloralose anesthesia or com- 

 pletely awake. Stimulation in these areas may be 

 accompanied by a full-blown pattern of responses 

 including altered respiration and running movements 



