KENNETH KENT, PETER DEMPSEY, ZENA MCCALLUM AND THEODORE COOPER 
621 
bath. Modified Krebs-Ringer solution of the 
same composition as cited above was equili- 
brated at 25°C with a 95% Oo and 5% CO2 gas 
mixture in a remote column. The pH of the solu- 
tion was 7.4. The Krebs was circulated to the 
muscle bath from the column by gravity and a 
return pump. The muscles were stimulated by 
two fine platinum electrodes near the base of 
each muscle at 12/min and approximately 5% 
above threshold voltage. The resting tension of 
the muscle was the tension at the peak of the 
length-tension curve. The first derivative of the 
tension (dT/dt) was obtained on-line. 
For the hypoxia studies, after control tension 
measurements were made, the equilibrating gas 
mixture was changed to 5% O2, 5% CO2, and 
90% N2. The PO2 of the Krebs solution was re- 
corded in the following manner : 0.3 ml/min of 
the bath solution was suctioned from a port in 
the bath near the muscle and directed to a Lu- 
cite cell which held a Clark oxygen electrode. 
The electrode was calibrated before and after 
each experiment with known gas mixtures. The 
pOo was continuously recorded on an oscillo- 
graph. 
Two muscle preparations were studied simul- 
taneously in identical muscle baths. The proto- 
col of the experiment was as follows : The mus- 
cle was first bathed in Krebs solution under 
high oxygen tension. Developed tension and 
dT/dt at Lmax were determined after one hour 
of equilibration. The equilibrating gas mixture 
was then changed to the low oxygen one and de- 
veloped tension and dT/dt were measured after 
one hour in hypoxia. 
Tension, dT/dt, and PO2 were continuously 
recorded on a Sanborn 350 direct writing oscil- 
lograph. Tension development and dT/dt were 
expressed as per cent change from baseline. 
Transmembrane Action Potentials 
Action potentials were recorded by means of 
3M KCl-filled glass microelectrodes with a tip 
resistance of 5 to 20 megohms. The recording 
system consisted of a Bak standard wideband 
electrometer (Electronics for Life Sciences) 
and a Tektronix model 502 dual beam oscillo- 
scope. All data during an experimental run 
were recorded on a multichannel Hewlett-Pack- 
ard 3955 tape system. 
RESULTS 
Twenty-one days following the operative pro- 
cedure, the tissue catecholamine content was at 
its minimum < 0.01 /xgm/g tissue. At that time 
there was no response to tyramine. 
Interactions of Neural Transmitters 
The suprasensitivity of chronically dener- 
vated feline hearts was previously described in 
our laboratory.^ When norepinephrine (NE) 
was administered to isolated whole heart prepa- 
rations, the responses to a given dose of NE 
were greater in the chronically denervated 
hearts than in the hearts from control animals 
(Figure 1) . 
Responses to Hypoxia 
Right ventricular papillary muscles when 
subjected to hypoxic perfusing solutions demon- 
strated decreased contractility. As the PO2 of 
the Krebs solution was decreased to 120 mm Hg 
(5% O2) the developed isometric tension de- 
creased 32 ± 3% (average ± SEM) in control 
myocardium. However, the developed tension of 
RESPONSE OF CAT HEART TO NOREPINEPHRINE 
I I I I I 
I X 10"9 5 X 10"9 1 X 10"8 5 X 10"8 
g 
Figure 1. — Dose-response curves for norepinephrine in 
the normal versus denervated feline heart. The per- 
cent of maximum response for the isolated whole 
heart is shown as a function of the norepinephrine 
dose in grams. The mean responses and ± SEM are 
shown for normal (•) and chronically denervated 
(o) hearts. This figure is reproduced with the permis- 
sion of American Physiology Society. 
