996 
ANIMAL DISEASES 
Ductus Diverticulum 
^Mj= - I 478 
1 1 1 1 \ 1 1 1 1 1 1 1 1 1 1 1 1 
-8-7-6-5-4-3-2-1 0 I 2 3 4 5 6 7 8 
Liobility to Defective Ouctol Closure m Threshold Stohdord Deviation Units 
Figure 3. — Threshold model of hereditary patent duc- 
tus arteriosus 
The distribution of liability to defective ductal closure 
in offspring of 3 types of matings is compared. The 
location of the mean liability of each group is indi- 
cated as measured from the lower threshold for 
defective ductal closure (threshold between normal 
and ductus diverticulum). The mean liability of 
offspring of matings between PDA dogs and normal 
dogs with no family history of PDA (PDA X N) 
lies below the lower threshold, while the mean lia- 
bility of offspring of matings between 2 dogs with 
PDA (PDA X DPA) lies well above the thresh- 
old for PDA. The mean liability of offspring of mat- 
ings between PDA dogs and the first degree relatives 
of dogs with PDA [PDA X N (1° Rel. PDA)] lies 
about half way between the other 2 means. The r 
pears to be mediated by the increase in blood 
oxygen tension which follows the onset of 
breathing. The response to oxygen is demon- 
strable both in the intact fetus^" and in the 
isolated perfused ductus arteriosus. ^^'^^ While 
norepinephrine, acetylcholine,^" and brady- 
kinin-^ have also been shown to cause con- 
striction of ductal smooth muscle, there is no 
evidence that these agents play a major role in 
the normal physiologic closure mechanism. An- 
atomic closure of the ductus arteriosus occurs 
over a period of weeks after birth, through an 
extensive reorganization of the histologic struc- 
ture of the ductal wall. The vessel is eventually 
reduced to a fibrous strand, the ligamentum ar- 
teriosum. While histologic obliteration may be 
in part dependent upon initial closure of the 
vessel by active constriction, in theory PDA 
could result from a disturbance in the mecha- 
nisms responsible for either physiologic or ana- 
tomic closure. 
Knight et al. have recently studied the phys- 
iologic closure mechanism in isolated perfused 
ductuses from near term fetal pups genetically 
predisposed to PDA.^^ The ductal lumen size 
under conditions of hypoxia was greater than in 
ductuses from normal controls, and there was 
an absent or diminished constrictor response to 
oxygen, norepinephrine, and acetylcholine. In 
studies of the histologic architecture of the duc- 
tus arteriosus, Buchanan et al. have noted that 
pups from matings of dogs with hereditary 
PDA have a ductal wall structure which differs 
from that of controls of similar age.^'^^ There 
is a deficiency and abnormal distribution of 
smooth muscle cells, particularly evident in the 
segment of the ductus arteriosus which adjoins 
the aorta, and extending a variable distance to- 
ward the pulmonary artery. Elastic fibers are 
increased in size and number. The affected seg- 
ment resembles the wall of the adjacent aorta. 
Based on this evidence, it has been hypothe- 
sized that the multiple genes responsible for he- 
reditary PDA in the dog act in some way to ex- 
tend aorta-like differentiation to the ductus 
arteriosus.^ According to this concept, increas- 
ing liability to PDA represents extension of the 
values represent the proportion of genes each group 
of offspring has in common with dogs with PDA. 
Reprinted from reference #6 with permission. 
