738 
PHARMACOLOGY 
10 - 
10"^ 10"'* 10'^ 10'^ 10"' I lO' 10^ 
DOSE ACETYLCHOLINE (^g/ml) 
Figure 3. — a) Average acetylcholine dose response 
curves of isolated right atrial myocardium stimulated 
at 30 contractions per minute. 
As Figure 4 illustrates, when the pH is low- 
ered, the force-velocity curve is depressed and 
shifted downward and to the left. At all ages 
studied, for both normal and acidotic muscles, 
norepinephrine produced a marked increase in 
tension and in the velocity of shortening at any 
tension, and the absolute increase was similar 
under both conditions. However, despite this 
marked augmentation in contractility, when the 
pH was reduced, there was substantially less 
force generation and velocity of shortening 
than heart muscle at a normal pH. These find- 
ings indicate clearly that acidosis produces a 
shift in norepinephrine dose responsiveness, 
even in the absence of hypoxia. 
After Atropine (I jxg/ml) 
\ 
z — A /[Mature Fetal 
f Lamb (12) 
70 - 
10"^ 10"'' 10"^ 10'^ 10"' I lO' 10^ 
DOSE ACETYLCHOLINE (/ag/ml) 
b) Average acetylcholine dose response curves of 
isolated right atrial myocardium after pre-treatment 
with atropine. The numbers in parentheses are the 
numbers of animals from which cardiac tissue was 
obtained. Vertical bars: S.E.M. 
Propranolol 
Since age related differences in myocardial 
responsiveness to norepinephrine were observed 
it was considered important to examine the age 
dependency of the effects of a beta adrenergic 
antagonist, propranolol. Propranolol possesses 
other actions besides producing blockade of beta 
receptors.^ Examination of the fetal curve in 
Figure 5 reveals, especially, the direct depres- 
sant effects of propranolol on the myocardium. 
This negative inotropic action is also seen in the 
adult curve, but in the adult propranolol exerts 
a small, direct, positive inotropic action before 
it depresses contractility. Thus, at any concen- 
tration of the beta blocker, the fetal heart is 
significantly more depressed than the adult. De- 
spite this age-related difference in sensitivity to 
the inotropic effects of propranolol, we observed 
that the beta blocking action of the drug is the 
same for fetus and adult. 
