148 
CARDIAC MODELS 
TENSION 
6 
4 
2 
0 
60 

1 
i — I. — i — i. i 
^ 
0 1-^ 
TIME 
TO 
PEAK 
TENSION 
MSEC 
500 - 
400 
300 
12 18 24 30 36 42 
FREQUENCY OF CONTRACTION-STIMULI /MIN. 
Figure 8. — Force-frequency relations in the three 
groups of muscles. Average maximum isometric ten- 
sion (top), rate of tension development (middle), 
and time from stimulation to peak tension (bottom) 
are shown as functions of the frequency of contrac- 
tion. The numbers in parentheses = number of ani- 
mals in each group. Vertical lines with cross bars = 
± 1 SEM. (Reproduced with permission from the 
American Heart Association, Inc. from Circulation 
Res. 21:341, 1967.) 
ically, the increments in tension produced by 
paired electrical stimulation were significantly 
reduced from the normal value of 3.8 ± 0.3 
gms./mm, sq. to 2.2 ± 0.4 gms./mm. sq. in the 
muscles from cats with failure. 
When the frequency of contraction was pro- 
gressively increased from 6 to 48 stimuli/ 
minute in muscles obtained from normal, 
hypertrophied and failing cats, there was a 
progressive elevation in both rate of tension 
rise and tension (Figure 8) ; whereas, the time 
from stimulation to peak tension was shortened. 
However, the increments in the rate of rise of 
tension in response to changes in frequency 
were severely depressed in the muscles from the 
hypertrophied and failing hearts. The increase 
in the rate of rise per increment in frequency 
per minute averaged 0.43 gms./mm. sq./second, 
0.13 gms./mm. sq./second and 0.07 gms./mm. 
sq./second in the muscles from normal, hyper- 
trophied and failing hearts respectively. Thus, 
the positive inotropic effects of increasing fre- 
quency of contraction were muted in hypertro- 
phied and failing heart muscle. 
The third positive inotropic intervention was 
the addition of strophanthidin to the muscle 
contracting isometrically at the apex of the 
length-tension curve. Strophanthidin, 1.0 mi- 
crograms/ml., was added to the bath and the i 
maximal effect, which occurred 20 minutes 
later, was recorded. Following strophanthidin, 
the maximal tension achieved was 0.7 gms/mm. 
sq. a value significantly less than the normal 
value of 8.4 ± 0.5 gms./mm sq. (Figure 9). 
Thus, in addition to the depression of the 
functional level of the contractile state, muscles 
obtained from animals with ventricular hyper- 
trophy and heart failure also have depressions 
of response to positive inotropic procedures. 
The absolute changes in force and rate of force 
development produced by paired electrical stim- 
ulation increased frequency of contraction and 
strophanthidin were less in muscles from hy- 
pertrophied and failing hearts than in muscles 
from normal hearts. Furthermore, although the 
ISOMETRIC 
TENSION 6 
Figure 9. — Effects of the addition of 1.0 /xg/ml stro- 
phanthidin on maximum isometric force of contrac- 
tion at Lma:. in the three groups of muscles. The 
hatched area of each bar represents the average con- 
trol force, the clear area represents the average incre- 
ment following strophanthidin; the upper limit of 
each bar indicates the average maximum isometric 
tension achieved following strophanthidin. Vertical 
lines with cross bars = ±1SEM; numbers in par- 
entheses = number of animals in each group. (Re- 
produced with permission from the American Heart 
Association, Inc. from Circulation Res. (21:341, 
1967.) 
