492 



HANDBOOK OF PHYSIOLOGY ^^ CIRCULATION I 



60 - 



50 



40 



50 



20 



10 - 



5 10 15 20 25 30 35 40 



though, as is often the case, other values may be 

 more convenient to determine experimentally. 



The relations expressed by these curves constitute 

 a descripti\e analysis of what is meant by hetero- 

 metric autoregulation. As end diastolic pressure 

 increases there is an increase in stroke work which is 

 large relative to the pressure increase (curve .-1). If 

 one assumes the steep portion of the curve to be that 

 which is normally operative (as for example in the 

 various phases of the respiratory cycle), then it may' 

 be seen that large changes in ventricular stroke work 

 can be obtained without extensive changes of the 

 pressure necessary to fill the ventricle or the pressure 

 in the atrium and veins behind it. This fact is facili- 

 tated by the upward concavity of curve B, i.e., the 

 relatively large changes in fiber length brought about 

 by small pressure changes in the ventricle on the 

 lower, sensitive portion of this curve. 



Changes in myocardial contractility . Figure 2 shows two 

 ventricular jimclion curves obtained from a heart 

 paced at a constant rate of 140 per min. The first 

 curve (C) was obtained before and the second curve 

 {NE) was obtained during the administration of 0.36 

 gamma per min of norepinephrine. The dashed lines 

 connect the points relating mean left atrial (LA) 

 pressure to LV stroke work; the solid lines connect 

 points relating LVED pressure to LV stroke work. 

 Both VFCla and VFClv are shifted to the left during 

 norepinephrine. From any given LVED pressure, 

 the left ventricle produces not only- more stroke work 

 but also more stroke power and, in eacli instance, 

 high speed tracings reveal that tlu- rate of de\rlop- 



ment of tension is greater from any given L\'ED 

 pressure during the administration of norepinephrine. 

 An increase in contractility has, therefore, taken 

 place. It was noted that as long as the norepinephrine 

 infusion was maintained, the left ventricle continued 

 to exhibit heterometric autoregulation along the 

 curve NE. When the norepinephrine was withdrawn, 

 the heart again exhibited heterometric autoregulation 

 along curve C. It is, in fact, fair to say that each heart 

 continually exhibits heterometric autoregulation on 

 one or another of its ventricular function curves. The 

 shift from one curve to another will be determined 

 by whether an intervention which can cause such a 

 shift is imposed. Numerous other adrenergic agents, 

 such as metaraminol (97) and mephentermine sulfate 

 (123), have also been found to shift the VFCl.\ to 

 the left even though aortic pressure is held constant 

 throughout and the increase in stroke work is ac- 

 complished solely by increasing stroke volume. The 

 use of ventricular function curves as a means of 

 describing alterations in the performance charac- 

 teristics of the heart appears to have been found 

 useful in the analysis of the effects of digitalis (30), 

 hypothermia (65), surgical interventions on the 

 heart (117, 120), and an evaluation of the toxicity 

 produced bv agents used to achieve cardiac arrest 

 (63). 



HOMEOMETRIC AUTOREGULATION. A SCCOnd type of 



autoregulation occurs in the ventricle of the isolated 

 heart (99, 104). Unlike heterometric autoregulation 

 which occurs immediately, it requires at least se\eral 

 beats to develop fully and occurs after an increase in 

 ventricular activity such as that associated witii in- 

 crease in aortic pressure or heart rate. As a result of 

 the increase in myocardial contractility that follows 

 such an activit\ increase, the heart maintains an 

 L\'ED pressure and fiber length more nearly like that 

 which obtained prior to the activity increase than it 

 would ha\e if this type of autoregulation had not 

 taken place. It is therefore referred to as homeo- 

 metric autoregulation. As a result, the heart is 

 endowed witli performance characteristics, such tiiat 

 it can expel the same or nearly the same stroke 

 \olume against a wide range of resistances witiiout 

 more than a brief in\asion of its heterometric reser\-e. 

 In 1 91 2, Anrep observed that when aortic re- 

 sistance was elevated in the heart-lung preparation, 

 ventricular volume at first increased but then sub- 

 sequently declined. An influence appeared to him to 

 be operating soon after the initial dilatation which 



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