WILLIAM F. FRIEDMAN 
737 
NOREPINEPHRINE 
Figure 1. — a) Average norepinephrine dose response 
curves of isolated right ventricular myocardium ob- 
tained from 17 fetal lambs and 11 adult sheep. Verti- 
cal bars: S.E.M. 
NOREPINEPHRINE 
b) Average norepinephrine dose response curves of 
isolated right ventricular myocardium obtained from 
6 newborn lambs less than 3 days of age and 6 new- 
borns ranging in age from 3 days to 3 weeks. Verti- 
cal bars: S.E.M. 
line, depresses atrial contractions. Figure 3 il- 
lustrates our data concerning the effects of 
1 acetylcholine on myocardial contractility. These 
|i dose response curves demonstrate that the neg- 
jj ative inotropic effects of acetylcholine on iso- 
lated atrial myocardium is similar in the fetal 
lamb when compared to the adult sheep. Fur- 
thermore, when the atria are pre-treated with 
atropine the responsiveness to acetylcholine is 
different at the two different ages. In this cir- 
1 cumstance, we are looking at the composite 
1 result of a number of acetylcholine effects. 
I First the muscarinic depression of contractility 
which is inhibited competitively by atrophine. 
Secondly, in high concentrations, acetylcholine 
may produce a positive inotropic effect by re- 
leasing catacholamines from sympathetic nerve 
endings in the heart. The separation after atro- 
pine of the fetal acetylcholine dose response 
curve from the adult curve may be another re- 
flection of reduced or functionally immature 
sympathetic innervation in the fetus, and re- 
duced norepinephrine release by acetylcholine. 
Acidosis 
It has been suggested that acidosis does not 
depress cardiac function in the newborn animal 
in the presence of an intact sympathetic nerv- 
ous system unless hypoxemia supervenes.^-'' 
Figure 4 is representative of a number of expe- 
riments in which force-velocity curves were 
constructed from isotonic, afterloaded contrac- 
tions at a high p02 before the addition of nor- 
epinephrine at a normal pH, and at a reduced pH 
of 7.1. Acidosis was produced by either increas- 
ing the pC02 in the muscle bath or by adding 
lactic or hydrochloric acid. Raising the pC02, 
analogous to respiratory acidosis, always de- 
pressed contractility more than by simulating 
metabolic acidosis. 
10-10 10-8 10-6 
ISOPROTERENOL 
Figure 2. — Average isoproterenol dose response 
curves showing equal responses for fetal and adult 
ventricular tissue. The numbers in brackets are the 
numbers of animals from which cardiac tissue was 
obtained. Vertical bars: S.E.M. 
