662 
PHYSIOLOGY 
the perfusion pressure in the isolated sinus 
node artery.^'^ It is likely that this represents 
the auxiliary mechanism by which blood pres- 
sure fluctuations promote A-V synchronization 
in the absence of an intact baroreceptor reflex 
arc. 
SUMMARY 
An animal model of isorhythmic A-V disso- 
ciation was developed in anesthetized dogs. 
Complete A-V block was produced by injecting 
95% ethanol into the A-V node, and the ventri- 
cles were paced at a rate close to the prevailing 
discharge frequency of the S-A node. 
Isorhythmicity occurred, such that the mean 
S-A nodal frequency became equal to the fre- 
quency of ventricular pacing. A-V synchroniza- 
tion persisted when the pacing frequency was 
varied over a small but definite range of fre- 
quencies. 
A-V synchronization was characterized by a 
periodic oscillation of the P wave back and 
jiorth across the QR? complex and a concomi- 
tant rhythmic variat on of the arterial blood 
pressure. 
Whenever the amplitude of the blood pres- 
oure oscillations was sufficiently attenuated, A- 
V synchronization ceased. Also, in more than 
half of the experiments, A-V synchronization 
could not be achieved after acute cardiac dener- 
vation. 
Isorhythmicity could be evoked by varying 
the arterial blood pressure or by stimulating the 
vagi as appropriate functions of the P-R inter- 
val. 
The principal mechanism for producing A-V 
synchronization in isorhythmic dissociation in- 
volves the following biological feedback control 
system: (a) the difference in timing of the 
atrial and ventricular pacemakers determines 
the P-R interval, (b) the P-R interval affects 
the stroke volume, (c) the stroke volume affects 
the arterial blood pressure, (d) the arterial 
blood pressure is the stimulus for the barore- 
ceptor reflex, (e) the baroreceptor reflex differ- 
entially affects the frequencies of the atrial and 
ventricular pacemakers, and (f) this changes 
the phase relationship between the two pace- 
makers, to close the control loop. 
REFERENCES 
1. Marriott, H. J. L. Atrioventricular synchroniza- 
tion and accrochage Circulation 14:38, 1956. 
2. Segers, M., Lequime, L., and Denolin, H. Synchroni- 
zation of auricular and ventricular beats during com- 
plete heart block. Amer. Heart J. 33:685, 1947. 
3. Levy, M. N., and Edelstein, J. The mechanism of 
synchronization in isorhythmic A-V dissociation. II. 
Clinical studies. Circulation 42:689-699, 1970. 
4. Brockman, S. K. Dynamic function of atrial con- 
traction in regulation of cardiac performance, Amer. 
J. Physiol. 204:597, 1963. 
5. Brockman, S. K. Cardiodynamics of complete 
heart block. Amer. J. Cardiol. 16:72, 1965. 
6. Levy, M. N., and Zieske, H. Mechanism of syn- 
chronization in isorhythmic dissociation. I. Experi- 
ments on dogs. Circ. Res. 27:429-443, 1970. 
7. Levy, M. N., and Zieske, H. Mechanism of syn- 
chronization in isorhythmic A-V dissociation. III. 
Computer model. Circ. Res. 28:23-33, 1971. 
8. Hashimoto, K., Tanaka, S., Hirata, M., and 
Chiba, S. Responses of the sinoatrial node to 
change in pressure in the sinus node artery. Circ. 
Res. 21:297, 1967. 
9. James, T. N. Pulse and impulse in the sinus node. 
Henry Ford Hosp. Med. J. 15:275, 1967. 
DISCUSSION 
L. R. Castillo, Miami Heart Institute, 
Miami Beach, Florida: Which type of pace- 
maker did you use for this experiment, a fixed 
rate or a demand pacemaker ? 
Dr. Levy : A fixed-rate pacemaker was used 
in the animal experiments. Actually, for the last 
several experiments that you saw on the slides, 
we were using the analogue computer itself for 
the pacemaker. In the earlier experiments we 
used just a Grass stimulator, and, of course, it 
would be fixed rate, but we would change the 
frequency. We would change it and let it stay at 
a new frequency. But this was not a demand 
pacemaker. The patients that we studied were all 
awaiting the insertion of a permanent pace- 
maker but we studied them at the time that 
they had the temporary fixed-rate pacemaker in 
place. 
Colin Grant, Albany Medical College, N.Y. : 
I may have missed some of the things that you 
said, but what effects did you find from phar- 
macological interventions in clinical material? 
Dr. Levy : We didn't do any pharmacological 
interventions in the patients. We did give some 
atropine in one patient and the results were 
