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The role of the posterior atrial ganglionated plexus (PAGP) in heart rate (HR) control was tested in unanesthetized dogs (n = 8). Resting HR was unchanged before (85 +/- 20 beats/min, mean +/- SD) versus after (87 +/- 18 beats/min) surgical ablation of these intrinsic cardiac ganglia (PAGPX). However, the peak tachycardia to a 30-s stressful stimulus was significantly increased (P < 0.05) from +53 +/- 22 beats/min before the denervation to +77 +/- 13 beats/min after PAGPX. Conversely, the peak HR increase during the stress after beta-adrenergic blockade was the same before (36 +/- 24 beats/min) versus after (38 +/- 14 beats/min) PAGPX. Moreover, the HR response to a neutral behavioral stimulus, which is mediated primarily by withdrawal of parasympathetic inhibition of the sinoatrial (SA) node, was unaltered by PAGPX. Thus the augmented tachycardia subsequent to PAGPX was attributable primarily to increased sympathetic action at the SA node. These findings indicate that a major role of PAGP parasympathetic neurons is to inhibit sympathoexcitatory effects on HR, probably either via interactions between neurons comprising the intrinsic plexus(es) or perhaps via presynaptic inhibition of sympathetic neurotransmitter release. This organization would allow parasympathetic ganglia within the PAGP to selectively modify sympathetic input to the SA node independent of direct vagal inhibition of pacemaker activity.

Although conventional models of the human atrioventricular (AV) node assume a single upper common pathway, animal studies demonstrate dual atrial inputs: an anterior input from the interatrial septum and a posterior input from the crista terminalis (running near the os of the coronary sinus in the posteroseptal region). We hypothesized that functionally distinct dual atrial inputs to the AV node also exist in humans and that the anterior input has a lower safety factor for impulse propagation. To evaluate this hypothesis, we examined 20 patients undergoing radiofrequency ablation of the slow AV nodal pathway for AV nodal reentrant tachycardia who underwent subsequent follow-up testing. After ablation near the os of the coronary sinus (and posterior to the compact AV node), 11 patients had no residual slow pathway conduction [SP(-)], whereas 9 did [SP(+)]. The effective refractory period of the fast AV nodal pathway (FP-ERP) and anterograde AV nodal Wenckebach (AVN-W) cycle length were significantly increased at follow-up in the SP(-) patients (FP-ERP = 336 +/- 71 vs. 387 +/- 103 ms, P = 0.02; AVN-W cycle length = 356 +/- 74 vs. 442 +/- 118 ms, P = 0.03) but not in SP(+) patients. Similarly among 10 patients undergoing radiofrequency ablation of a right posteroseptal accessory pathway (near the os of the coronary sinus), 5 developed impaired AV conduction: abnormal anterograde pacing-induced AVN-W cycle length in 4 patients and 2:1 AV nodal block in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

The experiments were performed to determine whether the neuromodulatory effect of substance P (SP) could be demonstrated in the isolated atrium. Strips from the right (RA) and left atria (LA) of normal (control) and denervated canine hearts were placed in an isolated muscle bath, and isometric muscle tension was measured. Inotropic responses to direct muscarinic stimulation were obtained with 1 x 10(-9) to 1 x 10(-8) M acetylcholine (ACh), and responses to stimulation of the intramyocardial intrinsic cardiac nerves (ICN) were produced with nicotine (Nic), 1.0-10 x 10(-6) M. The same drugs were tested in the presence of 1 x 10(-6) M SP, which had no significant inotropic effects of its own. Responses to ACh were unaffected by SP. The primary negative inotropic response to Nic was greatly attenuated by SP in both control and denervated atria, whereas the secondary positive response in control atria was unaffected. This inhibition was very pronounced in LA but less so in the RA. We conclude that SP appears to modulate the responses of the ICN to nicotinic stimulation in a manner similar to that previously observed in intact animals. This mechanism may provide a means of direct modification of efferent cardiac responses by afferent nerves within the heart itself.

Experiments were carried out to determine the extent to which the efferent cardiac vagus may modulate the discharge from atrial receptors when heart rate was not controlled. Stimulation of the vagus increased atrial pressure and the discharge from type-B atrial receptors. In order to determine the extent to which the increase in atrial receptor discharge was the result of the associated hemodynamic changes, studies were done in which the vagus was stimulated while heart rate was maintained constant using atrioventricular pacing, as atrial pressure was varied over a wide range by volume expansion. In paced hearts vagal stimulation depressed atrial contractile force but did not alter atrial receptor discharge when compared to paced hearts without vagal stimulation. These results indicate that the effect of vagal stimulation on atrial receptor discharge is an indirect one mediated through the rise in atrial pressure due to cardiac slowing rather than a direct effect on the atrial stretch receptor itself.

It is generally held that left atrial stretch (LAS) but not right atrial stretch (RAS) reflexly inhibits vasopressin release and results in a diuresis. To reexamine the influence of RAS on the release of vasopressin and on the behavior of antidromically identified supraoptic neurosecretory neurons, RAS and LAS were applied in pentobarbital-anesthetized cats. Weighted 20 or 30 g sutures were placed in the left atrium pulmonary vein junction and at the base of the right atrial appendage. Antidromically identified supraoptic nucleus neurons were inhibited by both RAS and LAS applied independently and together, although fewer neurons were responsive to RAS alone. Simultaneous stretch of both atria resulted in greater inhibition of these neurons than did stretch of either atrium alone. Stretch of the right atrium alone also resulted in a significant decrease in plasma arginine vasopressin measured by radioimmunoassay. Differences between these results and other reports may stem from differences in the method of RAS or the specific right atrial receptors affected.

Canine cardiac vagal ganglia in the region of the inferior vena cava and inferior left atrium (IVC-ILA) and at the junction of the right pulmonary veins and left atrium (PVFP) control atrioventricular conduction and heart rate, respectively. After retrograde transport of horseradish peroxidase (HRP) injected separately into these ganglia in different dogs, the left and right and longitudinal distributions of brain stem somata terminating in these ganglia were compared with functional dominance of left and right vagal control of heart rate and atrioventricular conduction. Labeled somata innervating these ganglia had quite similar longitudinal distribution patterns. Although functional dominance of heart rate was found to be in either the right vagus or bilaterally in both vagi, a corresponding difference in somata innervating the PVFP ganglia was not found. Functional vagal dominance of atrioventricular conduction was found to be either right, bilateral, or left with correspondence between left-right distributions of somata after HRP injection into the IVC-ILA region. However, these results should be cautiously interpreted because these ganglia mediate other cardiac functions.

To examine hindbrain pathways mediating release of adrenocorticotropin (ACTH) in response to hemodynamic changes we tested, in 19 cats (chloralose/urethan), 70 neurons in ACTH-active areas of the medulla for their response to volume pulsation (+/- 1 ml, 1 Hz, 60 s) of the right atrium (RA) or to hemorrhage (3 ml/kg per 30 s), and to electrical stimulation in ACTH-active areas of the dorsal rostral pons (DRP). The activity of 16 neurons was increased (P less than 0.05) by RA. Of these, 6 were driven antidromically from the locus subcoeruleus (LSC), and were located in the lateral solitary nucleus and in posteromedial nucleus intercalatus (NI). The activity of 11 neurons was decreased by RA. Of these, 5 were driven antidromically from LSC and lateral ventral tegmental nucleus and were located in anterolateral NI. No rostral projections were found to more medial sites in DRP. Responses to the first trial of RA were rapid, but slowed and attenuated with repeated trials. Responses to hemorrhage were rapid and in the opposite direction, but did not attenuate. The results suggest that pathways displaying rate sensitivity project from the right atrium via B-receptors to the DRP.

To examine the role of right atrial receptors in mediating reflex vascular responses we measured, in cats anesthetized with chloralose/urethan, changes in mean arterial pressure (MAP) in response to volume pulsation of the right atrium (+/- 1 ml, 1 Hz). Changes in MAP were measured 1) with pressure in the carotid arteries normal and vagus nerves intact: right atrial pulsation led to a very small and transient fall in MAP; 2) with pressure in the carotid arteries at 75 mmHg and the vagus nerves intact: right atrial pulsation led to a larger and sustained fall in MAP; 3) with pressure in the carotid arteries at 75 mmHg and the vagus nerves cooled or sectioned bilaterally: right atrial pulsation of the right atrium led only to a very small and transient fall in MAP. These data suggest strongly that signals from right atrial receptors traveling in the vagus nerves mediate a reflex change in MAP that is normally masked by signals from carotid receptors.

The combined effects of parasympathetic and sympathetic stimulation on right atrial contractile strength were assessed in open-chest, pentobarbital-anesthesized dogs. A factorial experimental design was employed to quantify the percent changes in atrial contractile strength in spontaneously beating and paced hearts as a function of the frequencies of vagal and stellate ganglion stimulation. In 7 of 10 dogs, there was a substantial interaction between the two autonomic divisions; the sympathetically mediated inotropic effect became less pronounced as the background level of vagal stimulation increased. The relationship between stimulation frequencies and atrial contractile strength was not significnatly altered by pacing the hearts.

Sinusoidal volume changes (+/- 1 ml) were applied at 1 Hz to the right or left atrium of 25 anesthetized cats. Changes in firing rates of single vagal fibers and in plasma ACTH and cortisol were observed in response to start and stop of atrial pulsation. Decreased activity of right atrial and/or septal B-receptors was associated with increased ACTH. Changes in left atrial B-receptor activity were associated with a change in ACTH only if right atrial/septal receptors or baroreceptors also changed their activity in the same direction. The activity of atrial A-receptors did not change in response to atrial pulsation. A quantitative analysis suggested strongly that right atrial and/or septal B-receptors dominate in the response of ACTH to hemodynamic stimuli. Arterial receptors appear less effective, and left atrial B-receptors appear least effective in the hemodynamic control of ACTH.

The purpose of this study was to determine whether cardiac receptors that are stimulated by veratrum alkaloids exert an inhibitory influence on the secretion of vasopressin (ADH). In six chloralose-anesthetized dogs, injection of cryptenamine (2 microgram/kg) into the circumflex coronary artery resulted in a significant (P < 0.05) fall in arterial pressure (-45 +/- 5 mmHg). Despite this hypotension and the presence of intact arterial baroreflexes, there was no change in plasma ADH (measured in the superior vena cava). In eight dogs with sinoaortic baroreceptor denervation, hemorrhage of 10 ml/kg decreased arterial pressure 20 +/- 5 mmHg (P < 0.05) and increased plasma ADH from 14 +/- 5 to 38 +/- 13 microU/ml (P < 0.05). Intracoronary injection of cryptenamine (1 microgram/kg) decreased plasma ADH to 23 +/- 7 microU/ml during the 5 min immediately after cryptenamine injection and to 16 +/- 4 microU/ml 20 min after injection. In eight dogs with sinoaortic denervation, hemorrhage and injection of vehicle resulted in a progressive increase in plasma ADH over the same time period. Vagotomy abolished the inhibitory response to cryptenamine injection. These data show that stimulation of cardiac receptors with vagal afferents by intracoronary injection of a veratrum alkaloid inhibits ADH secretion. Activation of these receptors can prevent arterial baroreflex-induced increases in ADH.

The right atrium has been shown to mediate release of ACTH in response to small hemorrhage. Therefore, we sought to identify hypothalamic neurons (cat, alpha-choloralose 35-45 mg/kg) wholse firing rates were modulated by stretch of the right atrial-vena caval junction. Stretch was produced by intermittent inflation of a balloon implanted between the pericardium and the right atrium. In some cases, carotid arteries were occluded bilaterally. Previous results indicate that electrical stimulation of the medial-dorsal hypothalamus (MDH) causes prompt changes in ACTH, but stimulation in the lateral hypothalamus does not cause changes. Of 64 cells recorded in the MDH, 41 responded to atrial stretch. However, only 2 of 18 cells outside this region responded. Six cells were studied with and without carotid occlusion. Their response was dimished or absent in the absence of carotid occlusion. The results suggest that integration of afferent signals from cardiovascular receptors occurs in the MDH and that the MDH may participate in neural mediation of ACTH in response to hemodynamic changes.

The potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in cardioacceleratory nonadrenergic noncholinergic (NANC) nerves was examined in the guinea pig right atrium in vitro. In the presence of atropine, a muscarinic antagonist, and atenolol, a beta-adrenoceptor antagonist, transmural nerve stimulation (TNS) of the isolated right atrium caused a positive chronotropic response, which is slow in both onset and decay. This TNS-induced slow response was assumed to be mediated by NANC nerves in the right atrium since tetrodotoxin inhibited the response. Dense distribution of CGRP-like immunoreactive (CGRP-I) nerves was demonstrated in the sinus node. Exogenously applied CGRP exerted a positive chronotropic effect on the isolated right atrium in a dose-dependent manner. Both CGRP-I nerves and NANC response induced by TNS were not affected by surgical sympathectomy and reserpine pretreatment but were abolished by the pretreatment of animals with capsaicin. The results suggest that CGRP is the neurotransmitter of cardioacceleratory NANC nerves in the right atrium of the guinea pig.

A chronically implanted inflatable balloon was used to produce distension of a left pulmonary vein at its junction with the left atrium in trained conscious dogs. Balloon inflation caused a fall in the amounts of water drunk in response to injection of isoproterenol, infusion of hypertonic NaCl, or overnight water deprivation. There was also a significant increase in heart rate, but arterial, central venous, and left atrial pressures were unaltered. Blockade of the left vagosympathetic nerve prevented the inhibitory action of distension of a pulmonary vein on water intake in response to injection of isoproterenol. In experiments where the balloon was left inflated for 24 h, distension also caused a fall in the spontaneous daily water intake, whereas food intake was unaffected. Despite the fall in water intake, urine flow increased so that the dog went into negative fluid balance. In conclusion, distension of a pulmonary vein at its junction with the left atrium causes reduction in both spontaneous and induced water intake, and this inhibition is not secondary to circulatory changes or fluid retention by the kidney. The action of the receptors concerned may complement the actions of the same or similar receptors on renal function whose effects have been observed previously in acute experiments in anesthetized animals and here for the first time in conscious animals.

Acute studies were conducted in cats to determine the effects of small changes in left atrial pressure (LAP) on the activity of antidromically identified neurons in the supraoptic nucleus (SON). Inflation of left atrial balloons reproducibly altered the frequency of 15% of the SON neurons. More than half of these increased frequency, probably due to a simultaneous increase in arterial pressure. In a second series, the firing rates of 20% of the SON neurons tested were inversely related to changes in LAP produced by pumping blood into or out of the left atrium. A third series of experiments were conducted in which the left atrium was directly stretched by pulling on a suture placed in the atrial wall in addition to one of the above methods of changing LAP. Directly stretching the left atrium inhibited over 70% of the SON neurons; this included all the neurons that responded to changes in LAP. The results suggest that these SON neurons have differential sensitivities to inputs from left atrial receptors.

Inflation of a balloon in the right atrium of 13 dogs resulted in salt and water retention not attributable to changes in GFR, RPF, filtration fraction, mean arterial pressure, left atrial pressure, or renal venous pressure. The response to right atrial balloon inflation was compared with the renal effects of constriction of the abdominal aorta above the renal arteries and constriction of the ascending aorta. Neither procedure evoked the same response as balloon inflation. Results suggest that the decrease in mean arterial pressure which accompanies balloon inflation accounts for only part of the decreased salt and water excretion. There was no significant difference between the responses of denervated and intact kidneys to right atrial balloon inflation. A binary response to stretching of the right atrium is suggested, both components apparently involving hormonal mediation.

The purpose of this study was to provide new evidence favoring the hypothesis that cardiovascular information from arterial baroreceptors is integrated with the nigrostriatal system that contributes to regulation of motor activity. Samples of extracellular striatal dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were collected by the technique of in vivo microdialysis and analyzed by high-performance liquid chromatography-electron capture detection. Rats were prepared with a guide tube placed in the caudate-putamen for subsequent insertion of microdialysis probes. During the 1st wk after sinoaortic denervation (SAD) or sham operation (SO), a microdialysis probe was inserted and perfused with Ringer solution at the rate of 2 microliter/min in the freely moving rats. Samples were collected every 20 min before and after injection of pargyline, 100 mg/kg ip. The results showed that SAD rats have approximately 50% less extracellular striatal DA, DOPAC, and HVA than SO rats (P less than 0.01). After blockade of monoamine oxidase activity with pargyline, striatal DA accumulated three times faster in SO than SAD rats suggesting DA synthesis is reduced in SAD rats. These data provide further evidence that the arterial baroreceptor system affects dopaminergic metabolism in the nigrostriatal system possibly as a means for integration of cardiovascular and motor activity.

Sympathetic pathways mediating chronotropic, dromotropic, and inotropic responses during ansae subclavia stimulation were determined by sequential dissection around major cardiac vessels. Right sympathetic (RS) projections influencing ventricular contractile force converge at the common pulmonary artery and within the pulmonary artery nerves (PAN). RS projections influencing left atrial contractile force course within the PANs. RS pathways to pacemaker and right atrial contractile tissue were localized between the superior vena cava and ascending aorta. RS projections influencing conductile tissue converge between the common pulmonary artery and proximal right pulmonary artery. Left sympathetic (LS) projections to ventricular contractile tissue were localized at the common pulmonary artery, within the PANs, and in the ventral lateral cardiac nerve (VLCN). LS pathways influencing heart rate and conductile tissue were localized at the left pulmonary artery and coursing between the right pulmonary artery and left superior pulmonary vein. LS projections to atrial contractile tissue were localized within the PANs and coursing between the right pulmonary artery and left superior pulmonary vein. We conclude that there are parallel, yet distinct, projections of sympathetic efferents to automatic, conductile, and contractile tissue of the canine heart.

Anesthetized dogs were pump perfused in a system that held systemic arterial pressure constant. Pulmonary arterial beds were pressurized, and the induced transient falls of systemic vascular resistance (SVR) were measured. An approximately linear relationship between percent fall of SVR and pulmonary artery pressure was obtained. Left atria and pulmonary venous beds were pressurized using square-pulse, staircase, and ramp wave forms, and changes in SVR were measured. The effect of varying the interval between stimuli was appraised. An approximately linear relationship was obtained for responses to square-wave left atrial forcing pressure (Pla). With staircase forcing, the change of SVR per unit change of Pla depended upon prestimulus Pla. With ramp forcing, responses increased approximately linearly with respect to the logarithm of the rate of pressure rise. Responses to square-wave stimulation varied directly with respect to the interstimulus interval. This study shows that left atrial-pulmonary vein baroreflexes are capable of producing substantial short-term falls of SVR, and that the response depends upon stimulus pressure, rate of pressure change, base-line pressure, and pressure history.

The functional distribution of the cardiac sympathetic nerves to the atria and their arrhythmiogenic effects were determined in 16 open-chest pentobarbital-anesthetized dogs. Shortening of refractory periods at four right and two left atrial sites during stimulation of the nerves was taken as a criterion of their distribution. Stimulation of right stellate ganglion, craniovagal, and right stellate cardiac nerves produced localized shortening on the right atrium, particularly at the sinus node area, and invariably induced sinus tachycardia. The recurrent cardiac nerve produced little shortening at all sites and less arrhythmiogenic effect. The left stellate ganglion and ventrolateral cardiac nerve affected only left atrial sites and induced atrioventricular junctional rhythm. The ventromedial cardiac nerve affected all sites and had no consistent arrhythmiogenic effect. The innominate nerve had no substantial effect. We concluded that the functional distribution of the cardiac sympathetic nerves is localized, and that rate, rhythm, and refractory period changes induced by stimulation of these nerves are characteristic of the area of distribution.