622 
PHYSIOLOGY 
CO 
E 
o 
^ 3 
z 
g 
-z. 
X 
o 
^ I 
X 
o • 
. V" 
• Normal 32 ± 3 
o Denervated %+ 14^4 
12 3 4 5 
CONTROL TENSION (arams) 
Figure 2. — Developed isometric tension in hypoxia as 
a function of tension under control (oxygenated) 
conditions. 
chronically denervated papillary muscles fell 
only 16 ± 4%. Figure 2 illustrates the devel- 
oped tension in hypoxia as a function of the 
control tension. The responses of papillary mus- 
cles from chronically denervated cats are 
shown. The time to peak tension (TTP) de- 
creased in the control muscles as hj^oxia v^^as 
induced 0.48 ± 0.03 msec to 0.39 ± 0.02 msec 
(p < 0.05). However, there were no changes in 
TTP in the muscles from chronically dener- 
vated cat hearts 0.43 ± 0.02 to 0.42 ± 0.03 
msec (p < 0.1). The effects on the shape of the 
transmembrane action potential (TAP), how- 
ever, were similar for the control and the 
chronically denervated papillary muscles (Fig- 
ure 3). Although there was a slight decrease in 
the resting potential of this example, this de- 
crease was not a constant finding. 
DISCUSSION 
Myocardial catecholamine depletion by ex- 
trinsic cardiac denervation has elucidated the 
complex interaction of the neural mediators 
acetylcholine and norepinephrine.^-^ Catecho- 
lamine depletion has also made it possible to 
separate the direct myocardial actions of 
bretylium,^ angiotensin II,*' analogues of angi- 
otensin II (10), and ouabain'^ from possible in- 
direct-NE releasing properties. 
As the myocardial adrenergic terminals de- 
generate, the properties of binding, reuptake 
and degradation of norepinephrine are lost. 
Therefore, in denervated hearts exogenously 
administered NE is inactivated more slowly, a 
change that causes larger responses to the nor- 
epinephrine. 
Responses to hypoxia of chronically dener- 
vated hearts are significantly different from 
control animals. The decrease in tension caused 
by hypoxia is less in the chronically denervat- 
ed-catecholamine depleted heart muscle. The 
mechanisms responsible for this difference are 
unclear. Scheur and Stezoski" have demon- 
strated that short-term reserpine pretreatment 
has a protective effect in rat hearts subjected to 
hypoxia. They hypothesized that this effect of 
reserpine was related to the increased glycogen 
content of the reserpinized myocardium (the 
dose schedule of reserpine used produced only 
small changes in norepinephrine content) . Sim- 
ilarly, there is an increased glycogen content of 
denervated canine hearts. 
Trautwein et al." first demonstrated the ef- 
fects of hypoxia on the transmembrane action 
potential — a decrease in the plateau phase 
Figure 3. — Transmembrane action potential (TAP) of 
an isolated papillary muscle from chronically dener- 
vated cat heart. The two curves are superimposed 
tracings of the TAP in control conditions — curve to 
the right — and the shortening of the plateau and de- 
creased slope of repolarization caused by hypoxia. 
The resting potential decreased slightly in hypoxia in 
this example, but the resting potential was usually 
not affected by this degree of hypoxia. 
I 
