626 
PHYSIOLOGY 
its use, as a means of following and early detec- 
tion of myocardial dysfunction. 
Linhart" has put in one short paragraph the 
essence of what ventricular function curves are 
all about, and therefore his statement is quoted : 
"The ventricular function curve relating end- 
diastolic volume or filling pressure (preload) to 
the external work performed by the heart 
(stroke work or volume) has generally been 
used when characterizing the pumping action of 
the heart.^-^ As end-diastolic volume and, 
therefore, end-diastolic fiber length increase up 
to a certain limit, the normal heart responds by 
a significant enhancement in its force of con- 
traction (Frank-Starling mechanism) i'^. This 
is represented on the ventricular function curve 
by a large increase in stroke volume or work rel- 
ative to small changes in end-diastolic volume 
or pressure. A change in initial fiber length, 
such as is caused by changes in heart rate (pac- 
ing) or afterload (angiotensin or methoxamine 
infusion,i2 gj^jf^ ^^le ventricular response 
to various points on the same curve, indicating 
that intrinsic contractility has remained con- 
stant. Sarnoff has shown, however, that the 
ventricle has a family of ventricular function 
curves (VFC), and that the response may be 
shifted from one curve to another by enhance- 
ment or depression of myocardial contractility.* 
An increase in contractility is indicated by a 
shift of the VFC upward and to the left of the 
control state; a depression of function is indi- 
cated by a shift downward and to the right." 
There have been many reports"-^^ describ- 
ing the hemodynamic consequences of changing 
the rate of ventricular contraction. Ventricular 
rate has been changed by electrically pacing ei- 
ther the right atrium, left atrium, right ventri- 
cle or the left ventricle. Sequential pacing has 
also been used. Interestingly, most of these 
studies have been conducted in patients and 
normal human subjects. Some experimental 
studies have been made in anesthetized dogs 
and only a few have been made in conscious ex- 
perimental animals. 
Electrodes for pacing have been placed at nu- 
merous sites on both the ventricles and the atria 
in order to study the effect of pacemaking site 
on cardiac output. Finney^^ showed that ven- 
tricular function was significantly diminished 
with ventricular pacing as compared to atrial 
pacing. Changes in left ventricular peak dP/dt, 
peak left ventricular pressure, cardiac output, 
stroke work and stroke power for any given 
pacing rate were all found to be significantly 
greater when left ventricular pacing was used 
instead of right ventricular pacing. The reduced 
left ventricular function with right ventricular 
pacing apparently was not due to change in my- 
ocardial contractility, heart rate, end-diastolic 
fiber length or changes in compliance. The au- 
thor suggested that dyssynergy of ventricular 
contraction had played an important role in this 
phenomenon. 
Klotz, Lister, Jomain, Hoffman and Stuck- 
ey" also demonstrated in their studies that 
cardiac output was greater with pacing 
from the left ventricle than from the right. On 
the other hand Starzl, Gaertner and Webb,^^ 
William-Olsson and Anderson,i^ Benchimol and 
Liggett,!^ and Fletcher, Theilen, Lawrence and 
Evans^® have found that at a given heart rate 
the site of ventricular stimulation did not influ- 
ence either cardiac output or arterial pressure. 
It now seems clear that, regardless of pacemak- 
ing site, cardiac output is not significantly af- 
fected by changing heart rate, especially 80 to 
180 beats per minute.^'^ The studies of Stein, 
Damato, Kosowsky, Lau, and Lister^® are illus- 
trative of this point. They showed in 1966 that 
there was no significant change in the cardiac 
index when the heart rate was increased by 
atrial pacing in ten normal male volunteers 
ranging from 25 to 45 years of age, either at 
rest or during exercise. 
AH studies agree that there is an almost linear 
decrease in stroke volume with increases in 
heart rate. There is also general agreement that 
left ventricular stroke work decreases with in- 
creasing heart rate. 
Gilmore, Sarnoff, Mitchell and Linden^" 
showed, using anesthetized dogs, that when the 
ventricle is caused to contract as a result of di- 
rect electrical stimulation, it produces less 
stroke work from any given left ventricular 
end-diastolic pressure than when atrial stimula- 
tion is used at that same frequency. They ob- 
served that at any given left ventricular pacing 
rate, left ventricular end-diastolic pressure was 
lower and the left ventricle produced less exter- 
