PHYSIOLOGIC AND PHARMACOLOGIC RESPONSE 
OF CHRONICALLY DENERVATED FELINE HEARTS 
Kenneth M. Kent, Peter J. Dempsey, 
Zena T. McCallum and Theodore Cooper* 
The terminal sympathetic nervous supply to the heart 
can be abolished by a technique of mediastinal neural 
ablation. As degeneration of the nerves occurs, the ca- 
techolamine stores of the heart are depleted. Fifty-four 
cats were subjected to extrinsic cardiac denervation 
through a right lateral thoracotomy under halothane 
anesthesia. Three to four weeks following the operation 
the hearts were removed and the isolated cardiac tissue 
was studied. The function of the whole heart was as- 
sessed on a Langendorff apparatus, and right ventricu- 
lar papillary muscles were studied in a myograph. At 
the time of study the hearts contained less than 0.01 
figm of norepinephrine per gram of heart. The trans- 
membrane action potential was recorded in some expe- 
riments by the use of KCl filled microelectrodes which 
had a tip diameter of approximately 2 microns. The 
isolated cardiac tissue following denervation was super- 
sensitive to norepinephrine, and this augmentation was 
felt to be a result of decreased reuptake of the humoral 
agent by the sympathetic nerve terminals. The response 
of the catecholamine depleted cardiac muscle to hy- 
poxia was different from control cardiac tissue. When 
normal papillary muscles were subjected to hypoxia, 
tension and rate of tension development decreased. 
When catecholamine depleted muscles were subjected 
to the same degree of hypoxia, the decrease in contrac- 
tility was less than that of the control muscles. Also, 
hypoxia changed the transmembrane action potential so 
that the plateau (Phase 2) was shortened. This oc- 
curred to the same degree in control and catecholamine 
depleted muscles. 
INTRODUCTION 
The technique of extrinsic cardiac neural 
ablation made possible the study of the physio- 
logical adaptation of chronically denervated 
hearts,^ the pharmacological interactions of the 
neural mediators, the trophic influences of 
the cardiac nerves* and the direct myocardial 
action of pharmacological agents which also re- 
lease myocardial norepinephrine.^ 
The sympathetic nerve fibers enter the heart 
around the great vessels as well as with the 
vagal cardiac nerves.^ The destruction of the 
* National Heart and Lung Institute Bethesda, Maryland 20014. 
sympathetic postganglionic nerve fibers as they 
enter the heart causes degeneration of the my- 
ocardial nerve fibers and loss of the adrenergic 
nerve terminals and the adrenergic neural me- 
diator — norepinephrine. The ganglia of the 
cholinergic system, however, lie within the 
heart, and severing the vagal cardiac fibers re- 
moves the preganglionic fibers only. The choli- 
nergic ganglia and the postganglionic fibers 
within the heart itself remain intact after ex- 
trinsic cardiac denervation. 
METHODS 
Extrinsic cardiac denervation was performed 
in the following manner. Male cats, 2.5 to 3.5 
kg, were given 0.4 mg atropine sulfate i.m., 
placed in a restraining bag, and administered 
fluorothane 3% (Fluotech 3) in oxygen by 
mask. When surgical anesthesia was reached, 
the animals were given succinylcholine 4 mg i.v. 
and the trachea was intubated. With the ani- 
mals on positive pressure respiration (Harvard 
Instruments) at a tidal volume of 75 ml, anes- 
thesia was maintained with V2 to 1% fluothane 
in a closed system. A right thoracotomy in the 
fifth intercostal space was performed under 
sterile conditions. The azygos vein was cauter- 
ized and cut. The right vagus and phrenic 
nerves were dissected and cleared from adja- 
cent tissue from the thoracic inlet to the dia- 
phragm for the phrenic nerve and to the azygos 
vein for the vagus nerve. The cardiac branches 
of the right vagus nerve which usually came off 
of the main trunk dorsal to the azygos vein 
were identified and cut. The thymus gland was 
removed in its entirety by dissection and cau- 
terization. The pericardium was opened. The 
aortic adventitia was stripped circumferentially 
at the root of the aorta. The aorta and aortic 
arch vessels were then stripped of their adven- 
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