This study examined the effects and interactions evoked by various combinations of parasympathetic (P) and sympathetic (S) stimulations on sinus node automaticity and atrioventricular (AV) conduction (both anterograde and retrograde) in 11 two-mo old anesthetized puppies. The respective effects of these autonomic maneuvers were assessed by covariant analysis using a linear regression model of the form Y = alpha 0 + alpha 1 X base line + alpha 2 X sequence + alpha 3 X S + alpha 4 X S2 + alpha 5 X P + alpha 6 X P2 + alpha 7 X (P X S).... The effects of parasympathetic and sympathetic stimulation, of the quadratic term S2, and of the interaction term (P X S) were highly significant (P less than 0.0001) on both sinus node automaticity and AV conduction (anterograde and retrograde). In contrast, the effect of the quadratic term P2 was significant on sinus node automaticity only. Sequence of stimulation whether (SP) or (PS) had no significant effect on either chronotropic or dromotropic properties. Furthermore, whereas augmented antagonism with parasympathetic predominance over sympathetic activity was readily demonstrable in the control of sinus rate, the reverse, i.e., augmented antagonism with sympathetic preponderance over parasympathetic activity, was found to apply to the control of AV conduction (both anterograde and retrograde). Hence, the nature and extent of parasympathetic-sympathetic interactions vary considerably, depending on which cardiac structure and/or function is under scrutiny. It appears that AV conduction is especially sensitive to modulation of sympathoadrenergic activity, whereas sinus node automaticity is particularly responsive to cholinomimetic influences.

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Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle lengths. Data relating recovery times and return to control conditions to prepacing cycle length, pacing cycle length, duration of pacing, site of pacing, and origin of rhythms were analyzed by covariance analysis. From the analyses, the relative contribution of the determinants are: the prepacing cycle length 73%, the site of pacing 3.5%, the pacing cycle length 2%, and the interaction of the site of pacing and pacing cycle length 1% for sinus node recovery time; and for slow atrioventricular junctional rhythm recovery time, the duration of pacing 40%, the interactions between the duration of pacing and the pacing cycle length 27%, and the prepacing cycle length 9%. A modified exponential decay model predicted 8 beats for return to prepacing conditions during sinus rhythm and 66-100 beats during atrioventricular junctional rhythm. We conclude that the single most important determinant of sinus node recovery time is the prepacing cycle length. Pacing cycle length and site of pacing have a significant but small influence on sinus node recovery time and duration of pacing, beyond 20 seconds, has no significant influence. In contrast, duration of pacing is the most important determinant of slow atrioventricular junctional recovery time. Another major determinant of slow atrioventricular junctional recovery time is the interactions between pacing cycle length and duration of pacing. Prepacing cycle length has a minor influence, and site of pacing has no influence, on slow atrioventricular junctional recovery time.

Blood pressure and heart rate were recorded in 15 anesthetized puppies (6-10 wk, 1-6 kg) and 18 adult mongrel dogs (greater than 1 yr, 18-26 kg) before and during acute blood pressure changes achieved with nitroglycerin or phenylephrine (4 and 8 micrograms/kg iv). Overall heart rate responses to blood pressure changes in adults were significantly (P less than 0.05) greater than those in puppies. Following control baroreflex responses, two multifiber efferent preparations from the discrete thoracic cardiac nerves (sympathetic, n = 48; parasympathetic, n = 18) were simultaneously recorded and analyzed by microprocessor. Severing of the nerves significantly attenuated the heart rate responses to blood pressure changes in puppies only, suggesting less redundancy of the neural regulation of the sinus node in the puppy. The pressure-induced reflex changes in the sympathetic or parasympathetic efferent nerve activities were not significantly different between adult dogs and puppies. There were no significant differences in reflex activities in right-sided (n = 29) vs. left-sided (n = 19) sympathetic nerves in either puppies or adult dogs. Preganglionic sympathetic fibers in puppies (but not adult dogs) were more responsive to blood pressure changes than were postganglionic sympathetic fibers. Thus baroreceptor reflex control in the puppy is less developed than in the adult canine heart, and the maturational difference in neural regulation of the heart is at or beyond the efferent nerve terminals.

The direct effects of gamma-aminobutyric acid (GABA) on the sinus node and its neural regulation were studied by selective perfusion of the sinus node artery (SNA) in 26 open-chest pentobarbital-anesthetized dogs. GABA (1-1,000 micrograms/ml, 2 ml, SNA) produced no direct effect on intrinsic sinus rate, but in several experiments (at 1 microgram/ml) it produced an inconsistent augmentation of the sinus tachycardia due to right stellate stimulation. At all other concentrations tested (10-1,000 micrograms/ml), GABA did not significantly alter the sinus node response to stellate stimulation. Local alpha-receptor blockade with phentolamine or muscarinic receptor blockade with atropine through the SNA prior to the perfusion of GABA did not change the sinus node responses. GABA (10-1,000 micrograms/ml, 2 ml, SNA) significantly attenuated (by 45-80% of control) the sinus bradycardia due to stimulation of the right vagosympathetic trunk. The sinus node response to selective perfusion of norepinephrine or acetylcholine (0.01 micrograms/ml, 2 ml, SNA) was not affected by GABA. The stellate augmentation (when present) and vagal attenuation were both antagonized by perfusion of picrotoxin (1,000 micrograms/ml, 2 ml, SNA). It is concluded that GABA does not exert any direct effect on the sinus node but may indirectly influence sinus rate by an effect on local nerves or ganglia.