Vago-vagal Reflex Research Articles

Recurrent Paroxysmal Complete Heart Block Induced by Vomiting

A woman had a 40-year history of vomiting associated with syncope. Spontaneous and induced vomiting was predictably associated with sinus bradycardia, paroxysmal atrioventricular block, and ventricular asystole. The clinical and laboratory studies carried out to illustrate the mechanism of this unusual complication of vomiting demonstrated it to be due to a vagovagal reflex initiated by distension of upper esophagus.

P-61 - Correlation between gastric relaxation and VIP and PHI output induced by a vago-vagal reflex

P-61 - Correlation between gastric relaxation and VIP and PHI output induced by a vago-vagal reflex

Vagally mediated gastric motor and emetic reflexes evoked by stimulation of the antral mucosa in anaesthetized ferrets.

1. In the urethane-anaesthetized ferret chemical (NaCl, NaOH or HCl) or mechanical (stroking) stimulation of the gastric antral mucosa evoked a decrease in corpus pressure and inhibition of contractions in the presence of guanethidine, adrenalectomy and sectioned greater splanchnic nerves. 2. The fall in corpus pressure was present following administration of atropine but was abolished by vagotomy. 3. Preliminary evidence, using 100 mM-NaOH as the stimulus, is presented that the effects on corpus motility are due to simultaneous activation of the vagal efferents supplying the intramural non-adrenergic non-cholinergic inhibitory neurones and inhibition of those supplying the intramural cholinergic neurones. 4. The possible roles of this antro-corpus vago-vagal reflex in the regulation of gastric emptying and in the prodromal phase of vomiting are discussed.

Vago-vagal activation of naloxone-sensitive non-adrenergic, non-cholinergic jejunal contractions in the anaesthetized cat.

Experiments were performed on chloralose-anaesthetized cats, pretreated with guanethidine and with ligated adrenals and sectioned splanchnic nerves. The animals were paralysed and artificially ventilated. Jejunal motility was recorded by an intraluminal balloon, as volume changes at a constant pressure. Cervical or abdominal vagal afferent stimulation was performed before and after the administration of atropine. In both circumstances jejunal contractions were elicited. The latency of onset and the duration of the responses were significantly shorter before than after atropine. Strength-duration and frequency-response relationships, respectively, did not differ significantly prior and subsequent to atropine. Naloxone (0.05-0.5 mg kg-1 i.v.) blocked these reflexly induced atropine-resistant jejunal contractions, as did section of the contralateral vagus. Possible mechanisms of action of these putative opioid receptor-mediated neurogenic effects are discussed. The present study demonstrates that non-adrenergic, non-cholinergic, naloxone-sensitive jejunal contractions can be elicited as a vago-vagal reflex, where the receptive field seems to be located within the abdominal cavity.

Involvement of gastrointestinal mechano- and intestinal chemoreceptors in vagal reflexes: an electrophysiological study

The role of gastrointestinal mechanoreceptors and intestinal chemoreceptors in the genesis of vago-vagal reflexes was assessed by recording single vagal efferent fibre discharge in the urethane-anaesthetized ferret during procedures known to activate discrete populations of gastrointestinal afferent fibres. Distension of the stomach, duodenum and jejunum was used to activate mechanoreceptors while perfusion of the intestinal loops with various chemical solutions was used to activate mucosal chemoreceptors. Mechanical stimulation of the stomach and/or intestine was effective in modulating vagal efferent discharge in 90% of units tested. The response (either excitation or inhibition of efferent firing) was characterized by its short-latency (< 1 s), slow-adaptation, and rapid return on removal of the stimulus. In contrast, chemical stimulation was much less potent evoking clear-cut responses in only 26 of the 109 efferent units. Luminal HC1 was the most effective stimulus accounting for 81% of the efferent responses although these were of long-latency (> 1 min), gradual in onset and poorly maintained. Other efferent responses to HC1 and hypertonic saline were characterized by a long-latency, sudden increase in discharge associated with the prodrome of vomiting. We conclude that while the mechanosensitive afferent input is well represented in terms of the genesis of vagal reflexes, the chemosensitive afferent input may be more important in behavioural aspects of visceral stimuli like vomiting.

Pancreatic secretory response to intestinal stimulants: a review.

In humans and many laboratory animals, protein digestion products such as peptides and amino acids and fat digestion products such as fatty acids and monoglycerides are potent intestinal stimulants of pancreatic enzyme secretion. The pancreatic enzyme response to these intestinal stimulants is related to the perfused load (amount per unit time) rather than to concentration. Both neural and hormonal pathways mediate the enzyme response to these intestinal stimulants. Enteropancreatic, cholinergic, vago-vagal reflexes are probably the most important mediators of the enzyme response to low loads of amino acids and fatty acids; hormones, such as cholecystokinin, seem to be the major mediators of the response to high loads of amino acids and fatty acids. Under physiological conditions it is probably the interplay of neural and hormonal mechanisms which regulates the pancreatic response to these stimulants. Gastric acid is the major regulator of postprandial pancreatic bicarbonate secretion. Secretion released by HCl is probably the most important physiological hormonal mediator of postprandial pancreatic bicarbonate secretion; its effect being potentiated by extrinsic (vagal) and intrinsic (intrapancreatic) cholinergic nerves and release of other hormones, such as cholecystokinin.

Effects of antral distension on pancreatic exocrine secretion in dogs: evidence for a short reflex.

In chloralose anesthetized dogs and decerebrated dogs whose pyloric sphincter was submucosally ligated, the pancreatic exocrine secretory response to antral distension was studied. Distensions of the antral pouch with Tyrode's solution and 0.1 N HCl caused graded rises in pancreatic flow and protein and bicarbonate outputs. The serum gastrin concentration gradually rose after the distention with Tyrode's solution, while no rise in serum gastrin was elicited by acid distension. After cervical vagotomy, a reduced pancreatic response persisted but no rise in the serum gastrin was seen. After splanchnicectomy following vagotomy, the pancreatic response became greater than before splanchnicectomy. This pancreatic response was observed even after caeliac and superior mesenteric ganglionectomies, but was completely abolished by an external tight ligature around the pyloric sphincter, or by administration of hexamethonium or atropine sulfate. The results suggest the existence of an antropancreatic short reflex in addition to a long route vago-vagal reflex.

Endoscopic retrograde cholangiography with a balloon catheter: analysis of 100 consecutive cases.

One hundred patients whose standard endoscopic retrograde cholangiographic studies gave poor visualization of the biliary tract were investigated using a balloon catheter introduced into the common bile duct by duodenoscopy to block contrast material leakage. Full diagnostic visualization was obtained in 90 patients, leading to accurate diagnosis in 88. In two other patients, the diagnosis was not confirmed. In ten patients the bile ducts were not filled because of balloon size (seven), vagovagal reflex (two), and fistula (one). There were no serious clinical complications. Laboratory studies following the procedure disclosed impaired liver function (three patients), hyperamylasemia (two), and leukocytosis (two) of 41 patients tested, and positive blood culture in three of 81 patients studied. When standard retrograde cholangiography fails to visualize the biliary tract, endoscopic retrograde balloon catheter cholangiography is a useful diagnostic procedure, associated with acceptable minor complications.

Electrophysiologic identification of preganglionic neurons in rat dorsal motor nucleus and analysis of vagus afferent projections

Electrophysiological studies on preganglionic neurons (PGNs) in the dorsal motor nucleus (DMN) of the vagus nerve has been hampered by technical limitations. Conventional electrical stimulation of the vagus nerve with cathodal square-wave pulses activates both preganglionic and afferent fibers. Thus, some PGNs cannot be identified because the anticipated antidromic responses would be blocked due to collision with those orthodromic responses evoked with shorter latencies by activation of fast-conducting afferent fibers. Projections of vagus afferent fibers to PGNs are difficult to analyse with conventional methods because a preceding antidromic response may affect an orthodromic response which has a slightly longer latency. A new stimulation method was designed, consisting of anodal triangular pulse stimulation and spontaneous-spike triggered stimulation. In chlorase-urethane-anesthetized rats, unitary responses of the DMN to electrical stimulation of the ipsilateral vagus nerve were recorded. When only an orthodromic response by a DMN neuron was recorded with conventional stimulation, application of anodal triangular pulse stimulation revealed an antidromic response, so that the cell in question could be identified as a PGN. Some neurons that produced only an antidromic response to conventional stimulation, revealed an orthodromic response on spontaneous-spike triggered stimulation, which blocked the antidromic response due to collision. With these procedures, orthodromic responses due to vagus afferent projections were recorded in 35% of the identified PGNs, mostly due to C and partly, A fiber activations. All these projections were polysynaptic in nature. In conclusion, one-third of the PGNs of the DMN are involved in vagovagal reflexes, which occur through multisynaptic pathways.

Effects of esophageal distension on canine pancreatic exocrine secretion

The pancreatic exocrine secretion responses to distension of the thoracic oesophagus were studied in chloralose anesthetized dogs and decerebrated dogs occluded the pyloric sphincter with submucosal ligature. In 79 of 149 distensions, the pancreatic outflow was increased by 70.6% of control value before the distension with latencies of one to five minutes. This response was accompanied by the increased protein and bicarbonate outputs of 83.1% and 303.0% of control value, respectively. In 68 of 149 distensions, the pancreatic outflow, protein and bicarbonate outputs were decreased by 23.2%, 17.1% and 29.1% of control value, respectively. After transthoracic vagotomy immediately above the diaphragm or administration of atropine, the increased response was abolished, but the decreased one was not. The decreased response was markedly reduced by guanethidine, and completely abolished after following adrenalectomy. Furthermore, it was completely abolished after splanchnicotomy, too. There was no relationship between the pancreatic exocrine secretion and the serum gastrin concentration before and after distension of the oesophagus. These results provide an evidence for the existence of the oesophago-pancreatic excitatory and inhibitory responses. The excitatory one is due to the vago-vagal reflex and the inhibitory one is due to the vago-splanchnic reflex.

Effects of Avian Pancreatic Peptide on Smooth Muscle Relaxations by Vasoactive Intestinal Peptide and Inhibitory Nerve Stimulation

Experiments were carried out to investigate whether avian pancreatic peptide (APP) antagonized relaxations of vascular and gastrointestinal smooth muscles induced by vasoactive intestinal peptide (VIP) and non-adrenergic, non-cholinergic inhibitory nerve stimulation using the cat submandibular gland, cat colon and dog stomach in vivo and several isolated smooth muscles in vitro. APP caused a dose-dependent inhibition of an atropine-resistant vasodilatation induced by chorda-lingual and pelvic nerve stimulation and by VIP. APP did not reduce VIP output induced by pelvic nerve stimulation. APP shifted the dose-response curve for VIP and the frequency-response curve for pelvic nerve stimulation to the right. The vasodilatation induced by isoproterenol or bradykinin was inhibited by somewhat higher doses of APP. APP failed to inhibit the vago-vagal reflex relaxation of the dog stomach. In guinea pig and rat fundic strips and in isolated chick rectum, APP did not exert any significant effects on relaxation caused by VIP or transmural stimulation in the presence of atropine and guanethidine. The result indicates that APP inhibits VIP-mediated relaxation of the vascular smooth muscle, but not that of the gastrointestinal smooth muscle. The inhibitory effect of APP on VIP-mediated vasodilatation is suggested to be due to the physiological competition.

Central and local actions of opioids upon reticulo-ruminal motility in sheep

The effects of opioids and naloxone on cyclical forestomach motility were determined in anaesthetized and conscious sheep. To assess central or peripheral opioid actions, differential routes of administration were used. Possible dynamic effects along the innervating vagovagal reflex arc were investigated electrophysiologically at the cervical level of the vagus nerve. Further, direct influences on the smooth muscle were evaluated in vitro on isolated longitudinal reticular strips. Additionally, the effects of some spasmogenic agents were studied for comparative purposes. In anaesthetized sheep, opioids depressed in an identical manner both the amplitude of spontaneous cyclical contractions and contractions evoked by electrical stimulation of the distal end of the cut cervical vagus. In conscious sheep, low doses of normorphine and loperamide inhibited frequency and amplitude centrally (20 micrograms/kg and 4 micrograms/kg via carotid artery respectively), whereas locally higher dose levels (200 micrograms/kg and 10 micrograms/kg via coeliac artery respectively) affected only the amplitude of cyclical contractions. Furthermore the opioid peptides Leu-, Met-enkephalin and [D-Ala2-Met5]-enkephalinamide preferentially depressed the amplitude of cyclical motility most efficiently if administrated via the coeliac artery. These results indicate the presence both of a central opioid action depressing frequency and amplitude and of a local opioid action depressing only the amplitude of cyclical reticulo-ruminal motility. Opioids did not alter the resting discharge of afferent tension units and similarly failed to modulate tone of reticular strips in vitro, suggesting that the opioids act locally on the intramural neuronal plexus, possibly by diminishing the output of excitatory transmitter. Whether substance P could play a role as a vagal excitatory transmitter besides the classically implicated acetylcholine has been discussed. The central opioid mechanism is probably not situated within the gastric centres but elsewhere in the brain. Naloxone (greater than or equal to 100 micrograms/kg, jugular vein) stimulated the frequency of cyclical ruminal motility only in well-defined experimental conditions, probably via a central mechanism.

Gastric-vagal solitary neurons excited by paraventricular nucleus microstimulation

Electrophysiological studies were performed to determine whether neurons of the nucleus of the solitary tract (NST) which receive sensory input from the stomach via vagal afferents are activated by microstimulation of the medial parvocellular division of the paraventricular nucleus of the hypothalamus (PVH mp). We found that 37% of the NST neurons orthodromically activated by gastric vagal nerve stimulation are also orthodromically excited by PVH mp microstimulation. Not only do these NST neurons receive convergent input from the PVH mp as well as gastric afferent input (vagal), but this input from the PVH mp may also bias the responsiveness of these NST neurons to incoming afferent information. This PVH mp influence on NST excitability is probably mediated by a direct, monosynaptic projection between these two nuclei. These data support the hypothesis that neurons in the PVH mp can control gastric function by altering the sensitivity of neurons which form the sensory limb of gastric vago-vagal reflexes. This ability of the PVH mp to bias the responsiveness of NST neurons to incoming vagal afferent information is probably mediated by a direct, monosynaptic projection between these two nuclei.

Reflex control of the gastric motility by the vagus and splanchnic nerves in the guinea pig in vivo

Gastric responses to electrical stimulation of the vagus and splanchnic nerves and to esophageal distension were observed in studies of the reflex control of the gastric motility in anesthetized guinea pigs in vivo. The gastric motility was inhibited by both vago-vagal and splanchno-vagal reflexes through the activation of non-adrenergic inhibitory nerve fibers and by splanchno-splanchnic reflex through the inactivation of the intramural cholinergic excitatory neurons. Distension of the lower esophagus caused a relaxation of the stomach which was mediated by an intrinsic reflex via intramural non-adrenergic inhibitory neurons. Furthermore, stimulation of the splanchnic nerve innervating the stomach seems to activate adrenergic inhibitory, cholinergic excitatory and probably some non-adrenergic inhibitory fibers.

Vagal afferent stimulation-evoked gastric secretion suppressed by paraventricular nucleus lesion

Studies were performed to evaluate the possibility that the paraventricular nucleus (PVN) of the hypothalamus modulates gastric acid secretion by changing the sensitivity of the gastric secretory control mechanism to vagal afferent input. Under pentobarbital anesthesia, 17 rats were prepared with esophageal and pyloric catheters such that the stomach could be perfused continuously on a flow-through basis. Thus, acid secretion could be monitored throughout the experiment. Stimulating electrodes were attached to the central cut end of the cervical vagus nerve. Unilateral stimulation of cervical vagal afferents resulted in a substantial increase in gastric acid secretion. This vagal afferent-mediated increase in acid outflow was suppressed following a single PVN lesion ipsilateral to the side of afferent stimulated output. Given the nature of PVN connections with brainstem regions responsible for the elaboration of vago-vagal reflexes, our results suggest that the PVN may control gastric acid outflow by changing the gain of gastric vago-vagal reflexes.

Multiple Sites for the Cardiovascular Actions of Fentanyl in Rats

We studied the cardiovascular effects of intravenously administered fentanyl in normotensive rats anesthetized with pentobarbital and artificially ventilated. Fentanyl induced an immediate and short-lasting fall in blood pressure and heart rate by an action on opiate receptors localized at vagal nerve endings. Bilateral vagotomy suppressed these effects. The bradycardia, suppressed by bilateral vagotomy and reduced by previous administration of atropine, seemed to be due to a vagovagal reflex. Inhibition of the sympathetic outflow may also occur, because in pithed rats fentanyl failed to lower blood pressure. This masks a direct central stimulation of sympathetic outflow, because in bilaterally vagotomized rats fentanyl induced an alpha-adrenoceptor-blocking drug-sensitive hypertension which was insensitive to adrenalectomy. In addition, stimulation of cardiac opiate receptors by high doses of fentanyl lead to bradycardia in pithed rats. We conclude that in the rat, fentanyl administered intravenously can act at three different levels on cardiovascular regulation: the vagal nerve endings, the brain, and the heart.

Type B atrial receptor discharge increases on opening a nonhypotensive arteriovenous shunt in the dog.

A vagovagal cardioacceleratory reflex is activated when an arteriovenous (a-v) shunt is opened in the dog. However, the receptors which initiate this reflex have not been localized. Type B atrial receptor excitation was considered to be a major component of this reflex. The effect of opening a femoral nonhypotensive a-v shunt (i.e., shunt open plus infusion of blood to compensate for the resultant fall in mean arterial and pulse pressure) on type B atrial receptor discharge and heart rate was therefore studied in seven anesthetized, artifically ventilated dogs with beta-adrenergic blockade. Right atrial and aortic blood pressures, heart rate, and type B atrial receptor discharge was studied before and after opening a femoral a-v shunt. On opening the a-v shunt there was a significant increase (44%) in the average activity of type B atrial receptors and a small, but significant (6.8%) increase in heart rate. A significant linear positive correlation was observed between the change in activity of type B atrial receptors and the shunt flow. The results suggest that type B atrial receptors may be one of the receptor groups that initiate this vagovagal reflex.

Vago-vagal reflexes to the colon of the anaesthetized ferret.

Electrical stimulation of the central end of the vagal communicating branch in the thorax at frequencies between 2 and 20 Hz elicited, after a latency of 7.2 +/- 0.8 s, large-amplitude colonic contractions. 5 Hz stimulation gave near maximal contractions and, because vomiting was more likely to occur at higher stimulus frequencies, was used as the standard stimulus for subsequent experiments. At this frequency the peak colonic contraction was 6.5 +/- 0.9 kPa. Following atropine the characteristics of the response to central vagal stimulation differed from that seen before atropinization. The latency was longer (45.7 +/- 8.2 s) and the amplitude greatly attenuated (0.7 +/- 0.2 kPa). Cooling the vagus nerves to 2 degrees C at a level either above or below the site of stimulation completely abolished both the cholinergic and the atropine-resistant colonic responses to central vagal stimulation. These results are consistent with the vagus containing two motor pathways to the colon which are reflexly stimulated by a vagal afferent input. The functional significance of these reflexes is discussed.

Exercise-induced airway obstruction.

Many previous discrepancies and conflicts concerning the pathophysiology of EIAO have been explained or reconciled by the observation that respiratory heat loss and concomitant airway cooling relate directly and probably causally to both the occurrence and magnitude of the airway obstruction that develops. Recent measurements have documented and quantitated observations made centuries ago. Controversy continues concerning the role of mediator release and the relative contribution of vago-vagal reflexes to the response induced by airway cooling. Recent attempts to study the effects of cooling on both the responsiveness and metabolic processes of airway smooth muscle may well ascend the phylogenetic scale to the intact organism, eventually allowing the testing of hypotheses raised along the way. Meanwhile, we think it likely that airway cooling and the response to it will represent another example of nonspecific airway responsiveness, and that the links between this stimulus and the subsequent response will be multifactorial. The relative roles and interactive potentials of diverse processes will make the next step in understanding difficult, though not impossible.

Different modes of action of substance P in the motor control of the feline stomach and pylorus.

In an experimental in vivo model to study gastropyloric motility in the cat a contraction of the stomach and the pyloric sphincter was regularly obtained in animals subjected to electrical vagal nerve stimulation or local intraarterial (i.a.) injection of substance P (SP). Much more infrequently contractile motor responses were recorded at splanchnic nerve stimulation. The contractile effects of SP were sensitive to atropine or local infusion of a SP analogue, (D-Pro2,D-Trp7,9)-SP, indicating that SP activated a final common cholinergic neuron in both stomach and pylorus. However, there seemed to be separate transmission mechanisms in these two regions based on the results of the physiological studies. The vagally induced pyloric contraction was noncholinergic, nonadrenergic, but sensitive to ganglionic blockade (hexamethonium) or the SP analogue, indicating involvement of SP in a peptidergic pathway to the sphincter. The infrequent splanchnically induced pyloric contraction was sensitive to atropine, the SP analogue or ganglionic blockade (hexamethonium) in favour of SP acting on a final cholinergic neuron in this system. On the other hand the gastric contraction, obtained at either extrinsic nerve stimulations or local i.a. injection of SP, was sensitive to atropine or the SP analogue but hexamethonium resistant. These findings suggest antidromic activation of SP-containing axon collaterals of the extrinsic nerves terminating on cholinergic neurons of the gastric wall. When afferent C-fibres of the vagal nerve were selectively activated by local heating, pyloric contraction and gastric relaxation were obtained via vago-vagal reflexes. After cervical vagotomy heating of the distal end of the vagal nerve elicited a gastric contraction, previously demonstrated to be atropine sensitive and hexamethonium resistant, but no pyloric motor response. This suggests that the antidromic activation mechanism was present only in the stomach, not in the pylorus.