THE CONTROL OF THE FUNCTION OF THE HEART 



nous type of ventricular contraction, since an increased 

 stroke volume also impinges on diastole if the per- 

 formance characteristics of the ventricle remain 

 unmodified (14, 79). The pertinent literature, limited 

 thougli it may be in terms of well-controlled experi- 

 ments, does not reveal examples of a physiologically 

 operative reflex that evokes tachycardia which does 

 not, either directly or indirectly, also simultaneously 

 evoke an increase in contractility. One might predict 

 that, if it occurs, it must be rare. It is equally difficult 

 to imagine that any operative reflex will produce an 

 increase in the ventricular work produced from any 

 given end diastolic pressure without simultaneously 

 producing an increase in ventricular power. At the 

 very least, it is now clear that carotid sinus hypo- 

 tension produces not only its well-known tachycardia 

 but also simultaneously modifies the performance 

 characteristics of the left ventricle so as to augment 

 both the stroke work and stroke power it produces 

 from any given L\'ED pressure. 



E. Interrelation of Intrinsic Mechanisms and 

 Extrinsic Influences 



It is clear that the left ventricle of the isolated heart 

 exhibits an increased contractility through homeo- 

 metric autoregulation when its activity is increased 

 simply by increasing the aortic pressure (fig. 3). It is 

 also clear that, starting at any given level of aortic 

 pressure, sympathetic stimulation increases con- 

 tractility in advance (fig. 13) and independently of an 

 increased aortic pressure (105). Both must, therefore, 

 be playing a role in producing the observed increase 

 in ventricular contractility induced by carotid hypo- 

 tension. It seems peculiarh' appropriate to the opera- 

 tion of the carotid sinus that its cardiac and peripheral 

 vascular effects interrelate so as to reinforce each 

 other and, further, that an increase in the norepi- 

 nephrine background resulting from sympathetic 

 stimulation facilitates the intrinsic mechanism of 

 homeometric autoregulation. 



It is now apparent that the Bowditch staircase 

 effect is operative in the adequately supported canine 

 heart and thus that an increase in rate will, of it.self, 

 either increase contractility or protect against the 

 extent to which contractility might otherwise di- 

 minish. It is also clear that, at any given heart rate, 

 sympathetic stimulation increases contractility. Both 

 must, therefore, be playing a role in producing the 

 observed increase in contractility when carotid pres- 

 sure is lowered in the normal organism. Again, it is 



appropriate for the operation of the carotid sinus that 

 these effects are reinforcing rather than opposing. 



Since the carotid sinus can, both directly and indi- 

 rectly, reflexly modify both the filling and the con- 

 tractility of the ventricles by such diverse means and 

 over such wide ranges, it invites a consideration of its 

 participation as one significant influence in the con- 

 trol of cardiac output in varying states. 



IV. C.^RDIOV.aiSCULAR RESPONSE TO EXERCISE 



A. Changes in Cardiac Output and A J' Oxygen Difference 



The greatest demands normally made on the cardio- 

 vascular system are during heavy exercise when 

 oxygen consumption and cardiac output reach their 

 peak values. The maximal oxygen intake has been 

 used as an effective measure of circulatory capacity 

 (66); the circulatory determinants in achieving the 

 maximal oxygen intake are cardiac output and 

 arteriovenous oxygen difference (129). In recent 

 studies in man, from standing rest to a workload 

 producing the maximal figure, the o.xygen consump- 

 tion increased 9.6 times; the cardiac output, 4.3 

 times, and the arteriovenous oxygen difference, 2.2 

 times (66). The increase in cardiac output was 

 achieved by a doubling of both stroke volume and of 

 heart rate. 



Although the relative roles of increased heart rate 

 and increased stroke volume in determining the 

 cardiac output response to exercise have recently been 

 challenged (90-92), it now seems clear that, at least 

 in leg exercise in the upright position, an increase in 

 stroke volume is as important as the increase in heart 

 rate (66). Even if, as thought by Rushmer et a/. (90, 

 91), stroke volume were only maintained during 

 exercise, it is highly unlikely that this same stroke 

 volume would get either into or out of the ventricle 

 if, at the increased heart rates, a simultaneous increase 

 of myocardial contractility had not also occurred. 

 More directly, a plot of the relation between left 

 ventricular end diastolic volume and stroke work 

 during rest and exercise does, in fact, reveal an 

 increased contractility after exercise is begun (25). 

 To maintain that an increase in heart rate is the 

 primary means by which the organism augments its 

 cardiac output during exercise, without specific 

 reference to a simultaneous influence on the per- 

 formance characteristics of the ventricle, is not in 

 accord with the available information. 



As mentioned above, the widening of the arterio- 



