D. F. PATTERSON 
1001 
but abnormal differentiation of the cellular ele- 
ments leading to disturbance of conduction. Re- 
gretably, this dog died before electrophysiologic 
studies could be made. Future investigation into 
the etiology, pathogenesis, and electrophys- 
iologic properties of the specialized conduction 
tissue in animals of this type are of great inter- 
est. 
James and Drake have studied the hearts of a 
group of eleven Doberman Pinschers which 
died suddenly.^ 1 They found focal degeneration 
of the His bundle, associated with cartilage and 
bone formation in the adjacent central fibrous 
body. Small coronary arteries in the area were 
narrowed. Six of the eleven dogs had a common 
ancestor and all were purebred Doberman 
Pinschers. The authors have hypothesized that 
sudden unexpected death in these dogs may be 
the result of a form of Adams-Stokes attack 
brought about by interruption of AV conduc- 
tion. If this hypothesis is correct, varying 
degrees of atrioventricular block might be de- 
monstrable in early stages of the disease. Un- 
fortunately, no electrocardiographic observa- 
tions have yet been reported. 
DISCUSSION AND CONCLUSIONS 
Epidemiologic and genetic studies have 
shown that the common anatomic forms of con- 
genital heart defects in the dog are caused by 
lesion-specific genetic factors which are concen- 
trated in certain breeds. The defects so far ana- 
lyzed are genetically complex. Like hereditary 
PDA in Poodles, most are probably polygenic 
"threshold" traits, having a discrete (discontin- 
uous) phenotype, determined by a more or less 
continuous underlying distribution of genetic 
factors. Although multiple in number, the genes 
involved appear to affect the growth and differ- 
entiation of the developing cardiovascular sys- 
tem in very specific ways. The genes for a given 
defect may be looked upon as polygenic sets, the 
individual members of which have additive ef- 
fects upon some underlying variable such as the 
concentration of some substance, or the rate of 
growth of some tissue element important in car- 
diac development. At some critical threshold 
value of the variable, the gross form of the de- 
veloping organ becomes abnormal. In the case 
of hereditary PDA, available evidence suggests 
that the underlying genetic determinants in 
some way cause an extension of aorta-like dif- 
ferentiation to the ductus arteriosus. The 
threshold for PDA is reached when this quanti- 
tatively inherited defect in histodifferentiation 
reduces the capacity of the ductus to constrict 
to a level at which physiologic closure can no 
longer occur. As might be expected, on careful 
examination the abnormal phenotype is seen to 
exhibit a continuous gradation of severity ex- 
tending below and above the threshold for 
PDA. The degree of severity is determined by 
the "dose" of genes predisposing to PDA. 
The demonstration that many of the common 
forms of congenital heart defects in the dog are 
hereditary and lesion specific has a number of 
important implications. First, it provides the 
most compelling evidence yet available in an an- 
imal species that cardiovascular malformations 
have a primary genetic cause. Parallel evidence 
in man has suggested this for some time^- but 
Figure 7. — Sequence of Epicardial Activation in a Dog with Type A Wolff-Parkinson-White Syndrome 
TOP: Epicardial surface maps, showing the sequence of activation of the anterior, left lateral, and pos- 
terior surfaces of the heart of a five year old English Cocker Spaniel bitch with Type A WPW syn- 
drome (Figure 6). Compare with maps of a normal dog below. The times of activation are indicated 
in the sequence key and lead II electrocardiogram. The earliest region of epicardial activation occurred 
posteriorly in the right ventricle, near the septum. There was no evidence of collision (fusion) of 
normal and anomalously conducted wave fronts at the ventricular epicardium. Histologic sections 
of the region of earliest activation confirmed the existence of a muscular atrioventricular bridge. 
Reprinted from reference #9, with permission of the American Heart Association, Inc. 
BOTTOM : Sequence of epicardial activation in a normal dog. The format is the same as the illustration 
above. Note that normal excitation begins in the middle of the anterior right ventricle near the in- 
terventricular septum and spreads centrifugally and from apex to base. The posterior right ventricle, 
which was activated prematurely in the dog with WPW above, is activated relatively late in QRS 
in the normal dog. 
Reprinted from reference #9, with permission of the American Heart Association, Inc. 
