660 
PHYSIOLOGY 
P-St 
(MSEC) 
1000- 
500- ) I 
A 
VAGAL 1°°° 
STIM. 
PERIOD 
(MSEC) 
Figure 6. — Isorhythmic dissociation produced in a bi- 
laterally vagotomized dog with complete heart block, 
produced by stimulating the distal vagi at a fre- 
quency which varied as a function of the P-St inter- 
val. The basal frequency of vagal stimulation was 1.1 
pulses/sec (St-St interval, or "vagal stimulation pe- 
riod", of 900 msec), which marks the maximum 
value of the deflection in the lower tracing. At the 
optimum P-St interval, the St-St interval was auto- 
matically decreased to about 200 msec; i.e., the fre- 
quency of vagal stimulation was increased to about 5 
pulses/ sec. The change in vagal stimulation with 
changes in P-St interval produced isorhythmic disso- 
ciation, as shown by the rhythmic changes in P-St in- 
terval to the left of arrow 1 and to the right of arrow 
2. When the frequency of vagal stimulation was not 
altered as a function of the P-St interval (between 
the two arrows), A-V synchronization ceased, as 
manifested by the saw-toothed P-St tracing. Time 
scale-downward deflections indicate 10 sec. intervals. 
P-St in the upper tracing), the vagal stimula- 
tion period was increased to a constant level of 
900 msec, (i.e., a basal stimulation frequency of 
1.1 pulses/sec) . At the maximum P-St interval 
observed (about 100 msec) when the P was in 
front of St, the vagal stimulation period was de- 
creased to about 200 msec (i.e., a frequency of 
about 5 pulses/sec) . 
It is evident from the figure that when the 
vagal stimulation frequency was varied as such 
a function of the P-St interval, isorhythmicity 
was achieved (left and right thirds of Figure 
6). Between the arrows, the gain of the func- 
tion was reduced to zero; i.e., vagal stimulation 
period was held constant at 900 msec. Under 
those conditions, A-V synchronization ceased, 
as manifested by the saw-tooth appearance of 
the P-St tracing. This indicates that there is a 
sustained difference between the spontaneous 
S-A nodal frequency and the ventricular pacing 
frequency. 
DISCUSSION 
In patients with isorhythmic dissociation, 
there is frequently a rhythmic variation in the 
P-R interval (Figure 1) and this is attended by 
concomitant changes in the arterial blood pres- 
sure (Figure 2) . Similar changes in the P-R (or 
P-St) interval and blood pressure are observed 
in dogs with isorhythmic dissociation (Figures 4 
and 5) . That the changes in arterial blood pres- 
sure are intimately involved in producing the 
A-V synchronization is suggested by the con- 
sistent observation that when the blood pres- 
sure variations are attenuated, isorhythmicity 
ceases (Figures 4 and 5). It is strongly sus- 
pected that the blood pressure is involved in A- 
V synchronization through reflex mechanisms, 
at least in part, because (a) synchronization 
can be elicited by varying the frequency of 
vagal stimulation as a function of the P-R in- 
terval (Figure 6), and (b) when the vagi and 
stellate ganglia are sectioned, synchronization 
cannot be achieved in more than half the ani- 
mals, even when the blood pressure oscillations 
are permitted to occur. 
The principal mechanism producing A-V syn- 
chronization in complete heart block is repre- 
sented by the diagram in Figure 7. In the upper 
left corner of the diagram are shown the two 
apparently independent pacemakers, the S-A 
node and the ventricular pacemaker. In the dia- 
gram, the ventricular pacemaker is shown not 
to be influenced by circulatory conditions, which 
would apply strictly to the example of an artifi- 
cial fixed-rate pacemaker. In the case of a natu- 
ral idioventricular pacemaker or A-V node (as 
VENTRICULAR 
PACEMAKER 
S-A NODE 
DELAY 
P-R 
INTERVAL 
S T R 
0 
K 
E 
VOL 
U 
M 
E 
PERIPHERAL 
RESISTANCE 
B A R O - 
RECEPTORS 
ARTERIAL 
P R ESSURE 
Figure 7. — Block diagram denoting the biological feed- 
back control system which causes the variable fre- 
quency atrial pacemaker (S-A node) to become 
synchronized with a fixed (relatively or absolute) 
ventricular pacemaker in A-V dissociation. 
