J. F. SPANN, JR. AND G. M. LEMOLE 
147 
is reduced, its duration remains unchanged, 
since the duration of the active state has been 
found to be directly related to the time to peak 
tension in isolated heart muscle.^" The finding 
that the time to peak tension is normal indicates 
that the depression of force in the failing heart 
muscle does not result from an abbreviation of 
the duration of active state, but only from a de- 
pression of maximal intensity of the active 
state. Furthermore, had the time to peak ten- 
sion been increased in the face of the reduction 
of the rate of tension development, the maximum 
force the muscle was capable of developing 
might have been preserved, at least in part. 
Since this potential compensatory mechanism 
was not utilized, the maximum isometric force 
developed by the muscle from the cats with fail- 
ure was markedly reduced. 
Force-velocity relations were examined in 
muscles from the three groups of animals : nor- 
mal, right ventricular hypertrophy, heart fail- 
ure (Figure 6). The initial muscle length were 
set by a constant small pre-load, and the effects 
on the velocity of shortening of progressively 
increasing a load was then determined. At each 
load the velocity of shortening was less in mus- 
cles from both those cats with hypertrophy and 
those with failure, and the entire force-velocity 
curve was shifted downward and to the left. 
The maximal velocity of shortening (Vn,ax) at 
a load of 0.5 gm./mm. sq. averaged 0.09 ± 0.08 
muscle lengths/second in normal muscles and 
was significantly lower averaging 0.65 ± 0.60 
muscle lengths/second in the muscles from cats 
with hypertrophy, V^ax was significantly lower 
in muscles from the cats with failure than in 
muscles from normal cats or those with hyper- 
trophy; the average value in cats with failure 
was 0.34 ± 0.06 muscle lengths/second. Thus, 
in cardiac muscle isolated from the hypertro- 
phied and failing heart, there is a severe 
depression of the contractile state which is re- 
flected by a downward shift of the force-velocity 
curve with substantial reduction of the intrinsic 
speed of contraction (Vmax). These findings 
further indicate a depression of the intensity of 
the active state in the muscle from the failing 
and hypertrophied heart. Also, it must be em- 
phasized that all of these abnormalities are in- 
trinsic properties of the cardiac muscle of the 
failing heart and are not dependent on the al- 
tered humoral or environmental factors, since 
they are present in vitro; and therefore, the 
chemical and physical conditions are controlled 
in an identical manner for all the groups 
studied. 
Inotropic Interventions 
After studying the abnormalities of the con- 
tractile state in hypertrophied and failing mus- 
cle, it was of interest to determine the reaction 
of these muscles to various positive inotropic in- 
terventions. The efi'ects of paired electrical 
stimulation, changes in frequency of contrac- 
tion and the addition of strophanthidin were 
therefore examined. 
Sustained post-extrasystolic potentiation pro- 
duced by paired electrical stimulation has 
been shown to be a powerful, positive inotropic 
intervention. However, the depression of the 
contractile state of the failing heart muscle 
could not be completely corrected by sustained 
paired electrical stimulation (Figure 7). Specif- 
ic i 1 
ID - 
30METRIC 
TENSION 
N RVH CHF 
(2 4) (10) (.10) 
Figure 7. — Effects of sustained postextrasystolic poten- 
tiation produced by paired electrical stimulation on 
the maximal isometric force of contraction at Lma% 
in the three groups of muscles. The hatched area 
represents control force with single electrical stimula- 
tion; the clear area above represents the augmenta- 
tion with sustained paired electrical stimulation. 
Numbers in parentheses = number of animals. Ver- 
tical lines with cross bars = ± 1 S.E.M. (Repro- 
duced with permission from the American Heart 
Association, Inc. from Circulation Res. 21:341, 1967.) 
