Vagal Blockade Research Articles

Role of central nervous system monoamines in cardiopulmonary effects of Althesin in rabbit and man

The steroid induction agent, Althesin, infused intravenously in light anesthetic doses in otherwise unsedated man (84 μg kg −1 min −1) and rabbit (140 μg kg −1 min −1) causes similar autonomic and somatic effects. In the rabbit, the rise in heart rate (mainly due to central vagal blockade) and the selective depressant effects on respiratory rate are independent of CNS 5-hydroxytryptamine and noradrenaline. The rise in arterial pressure and the fall in hindlimb conductance is dependent on CNS 5-hydroxytryptamine and noradrenaline synthesizing neurons, which are probably arranged in series. These findings provide a working hypothesis for the mechanisms of action of Althesin on central cardiopulmonary controls in man.

Relative roles of vagal and sympathetic effector mechanisms in the baroreflex control of myocardial contractility in conscious rabbits

The relative roles of vagal and sympathetic effector mechanisms in the baroreflex control of myocardial contractility have been assessed in the conscious normotensive and hypertensive rabbit. Graded increases in mean arterial pressure (MAP) were produced by inflation of a balloon occluder around the abdominal aorta. Stimulus response curves relating the change in MAP to the induced change in peak rate of change of left ventricular pressure (peak LV dP/dt) were produced when heart rate was allowed to change and when it was held constant by atrial pacing. These curves were repeated after sympathetic blockade with propranolol, vagal blockade with methylscopolamine and combined blockade with the two drugs together. Increase in MAP produced a reflex fall in peak LV dP/dt which was due to two components. There was a reflex negative inotropic effect which was independent of heart rate, occurring in animals in whom heart rate was held constant by atrial pacing, and there was also a reduction in peak LV dP/dt which was caused by the reflex bradycardia when the heart rate was allowed to change. Both sympathetic and vagal efferents contributed to the reflex fall in peak LV dP/dt seen after elevation of MAP, the sympathetic being primarily responsible for the direct negative inotropic effect and the vagus for the bradycardia and hence the secondary effects on peak LV dP/dt. The slope of the stimulus response curves relating the fall in peak LV dP/dt to the increase in MAP was similar in intact normotensive and hypertensive rabbits, both with and without atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Vasopressin on Heart Rate in Conscious Rabbits

The effects of vasopressin on heart rate and on the baroreceptor-heart period reflex were assessed during graded intravenous infusions of arginine vasopressin. Infusions which elevated plasma arginine vasopressin to 200 pg/ml had no effect on blood pressure, but induced a fall in heart rate and cardiac output and an increase in peripheral resistance. These effects were unaltered by vagal blockade with methylscopolamine and cardiac sympathetic blockade with propranolol but were prevented by pretreatment with a specific vascular antagonist to vasopressin, d(CH2)5Tyr(Me)AVP. Baroreflex control of heart rate was studied during vasopressin infusion by monitoring the heart period responses to graded changes in mean arterial blood pressure produced by inflation of balloon occluders around the abdominal aorta and thoracic vena cava. Elevation of plasma arginine vasopressin to 50 pg/ml and 200 pg/ml had no significant effect on the slope or sensitivity of the baroreceptor-heart period reflex but increased the maximum bradycardia elicited in response to large increases in blood pressure. We conclude that at physiological levels, arginine vasopressin has a direct cardiodepressant action that is not dependent on cardiac vagal or sympathetic activity. Our results indicate that arginine vasopressin increases the maximum bradycardia that can be elicited through baroreceptor reflexes but does not alter the slope relating change in heart rate to change in blood pressure.

Characteristics of secretin-stimulated pancreatic secretion in dogs.

The effect of the periodic interdigestive activity of the gut on secretin-stimulated pancreatic secretion was studied in eight conscious dogs each with a Thomas duodenal fistula, a gastric fistula and a Heidenhain pouch. Pancreatic water and bicarbonate responses to a small dose of secretin were greatly augmented in phase with the spontaneous periodic activity of the gut. This augmentation was closely related to pancreatic protein secretion. As the dose of secretin was increased the interval between peaks was prolonged, the peaks became less sharp, the nadirs were raised, and finally the periodic activity was no longer seen. Bilateral cervical vagal blockade with local anaesthetics reduced the secretin-stimulated bicarbonate secretion by 50% but the augmentation at the peak was not abolished. Atropine abolished the periodic augmentation completely and reduced the bicarbonate response by 80%. The peak response of volume and bicarbonate to secretin obeyed Michaelis-Menten kinetics. The nadir secretin dose response, however, was a sigmoid curve with a Hill coefficient larger than one. The action of atropine or hexamethonium was to shift the peak response kinetics to the nadir kinetics. It is concluded that the pancreatic response to secretin is greatly modulated by the spontaneous periodic activity of nerves.

Vagal control of gall-bladder contraction.

The role of the vagi in gall-bladder contraction was studied in conscious dogs with chronic biliary fistulae. The interdigestive periodic contraction of this organ was abolished by bilateral cervical vagal blockade, atropine or pentolinium, but neither methacholine nor carbachol initiated contraction when the duodenum was kept alkaline. The orthodox view that gall-bladder evacuation is primarily controlled by humoral mechanisms needs re-evaluation. Vagal blockade prevented the usual gall-bladder contraction in response to duodenal acidification.

Cardiac Performance in the Conscious Rabbit with Acute Hypertension Following Brainstem Lesions Coinciding with the A1 Group of Catecholamine Neurons

Electrolytic lesions of the ventrolateral medulla, coinciding with the A1 catecholamine cells of the conscious rabbit (A1 lesions) cause acute hypertension and bradycardia and in some animals, pulmonary oedema. We have assessed the change in cardiac performance after an A1 lesion, the role of cardiac autonomic effectors in this change: and the mechanism of the pulmonary oedema. Following A1 lesions there was a profound (over 100%) rise in total peripheral resistance and a fall in cardiac output which was mainly due to a fall in stroke volume since it occurred even in animals in which the heart rate was held constant by atrial pacing. This reduced stroke volume occurred despite a 40% increase in myocardial contractility (peak LV dP/dt) and elevation of left ventricular end diastolic pressure. β-Adrenoceptor blockade with propranolol abolished the rise in peak LV dP/dt, while vagal blockade with methylscopolamine abolished the bradycardia and combined blockade with propranolol and methylscopolamine abolished the rise in peak LV dP/dt and reduced the bradycardia. In rabbits which developed pulmonary oedema, left ventricular end diastolic pressure rose to 35 ± 3.5 compared to 16 ± 2.7 mmHg in those which did not, suggesting that the pulmonary oedema was due to raised left ventricular filling pressure. Journal of Hypertension 2:379-386, 1984

Cardiac Performance in the Conscious Rabbit with Acute Hypertension Following Brainstem Lesions Coinciding with the A1 Group of Catecholamine Neurons

Electrolytic lesions of the ventrolateral medulla, coinciding with the A1 catecholamine cells of the conscious rabbit (A1 lesions) cause acute hypertension and bradycardia and in some animals, pulmonary oedema. We have assessed the change in cardiac performance after an A1 lesion, the role of cardiac autonomic effectors in this change; and the mechanism of the pulmonary oedema. Following A1 lesions there was a profound (over 100%) rise in total peripheral resistance and a fall in cardiac output which was mainly due to a fall in stroke volume since it occurred even in animals in which the heart rate was held constant by atrial pacing. This reduced stroke volume occurred despite a 40% increase in myocardial contractility (peak LV dP/dt) and elevation of left ventricular end diastolic pressure. beta-Adrenoceptor blockade with propranolol abolished the rise in peak LV dP/dt, while vagal blockade with methylscopolamine abolished the bradycardia and combined blockade with propranolol and methylscopolamine abolished the rise in peak LV dP/dt and reduced the bradycardia. In rabbits which developed pulmonary oedema, left ventricular end diastolic pressure rose to 35 +/- 3.5 compared to 16 +/- 2.7 mmHg in those which did not, suggesting that the pulmonary oedema was due to raised left ventricular filling pressure.

Lower esophageal sphincter function in the cat: role of central innervation assessed by transient vagal blockade.

Studies were performed on four cats to assess the role of extrinsic vagal innervation in the control of lower esophageal sphincter (LES) function. Both cervical vagal nerves were blocked transiently by cooling. LES pressure was measured using a multilumen manometry tube. LES relaxation was assessed during intraesophageal balloon distension in both the striated and smooth muscle portions of the esophagus. Bilateral vagal nerve blockade lowered the mean LES pressure from 58 +/- 17 to 29 +/- 9 mmHg (P less than 0.01). During vagal blockade, balloon distension in the striated muscle esophagus further reduced sphincter pressure to 16 +/- 4 mmHg (P less than 0.01) and that in the smooth muscle esophagus to 15 +/- 3 mmHg (P less than 0.01). Swallow-induced LES relaxation was abolished during bilateral vagal nerve blockade. During vagal blockade, atropine reduced LES pressure to 10 +/- 1 mmHg, phentolamine to 13 +/- 6 mmHg, and hexamethonium to 10 +/- 4 mmHg (all P less than 0.01). We conclude that 1) normal LES tone in the cat is mediated primarily by two separate neural mechanisms: a vagal cholinergic mechanism and a nonvagal mechanism that utilizes both alpha-adrenergic and cholinergic receptors; 2) local, intramural mechanisms of high threshold are present in the striated and smooth muscle cat esophagus to allow distension-induced reflex inhibition of the LES; and 3) swallow-induced LES relaxation is dependent on vagally mediated central nervous system connections.

Respiratory responses to external resistive loads during vagal blockade in awake dogs.

The present study examined the possibility that mechanoreceptors in the chest wall structures (rib cage and diaphragm) contribute to the increase in the neuromuscular drive to breathe (occlusion pressure) when the load on the respiratory muscles is increased in conscious animals and humans. Studies were carried out in 4 awake dogs in which external resistive loads (12 cmH2O/L/s) were applied during inspiration to increase the load on the respiratory muscles. Loads were applied via a tracheostomy during complete vagal blockade performed by cooling exteriorized cervical vagal loops. The ventilatory and occlusion pressure responses to the load were compared over the same range of chemical drive by applying loads during CO2 rebreathing. During vagal blockade, inspiratory resistive loads had no consistent effect on the duration of inspiration or expiration and decreased the ventilatory response to hypercapnia by decreasing average inspiratory flow rate. In all animals, however, inspiratory loading increased the occlusion pressure (P100) response to hypercapnia. The P100 at PCO2 = 55 mmHg increased during flow loading in all 4 animals, and the slope of the change in P100 produced for a given change in PCO2 (delta P100/delta PCO2) increased in 3 of the 4. Flow loading had no effect on end-expiratory lung volume at rest and did not influence the decrease in lung volume observed during hypercapnia. The present study indicated that the neuromuscular drive to breathe, as assessed from the occlusion pressure, is increased in conscious animals subjected to ventilatory loads during vagal blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

AUTONOMIC INFLUENCES UPON ELECTROPHYSIOLOGIC PARAMETERS OF SINUS NODE FUNCTION IN IMMATURE PUPPIES: EFFECTS OF CHEMICAL SYMPATHECTOMY

To study the influence of sympathetic ingrowth on sinus node (SAN) function, 2 groups of puppies underwent electrophysiologic studies. Eleven puppies (20 studies, ages 3-17w, m 9.0) underwent chemical sympathectomy by 6 hydroxydopamine (60H). Twelve puppies (22 studies, ages 3-25w, m 10.9) were controls (C). Testing was repeated after atropine (A) and atropine and propranolol (A+P).Resting cycle length (CL) was shortened by A, in both C (p<.001) and 60H (p<.001). After A, differences of C1, sinoatrial conduction time (SACT), and corrected sinus node recovery time (CSNRT) between C and 60H were N.S. In C, CSNRT correlated with age (r=.61, p<.02); in 60H it did not.In C, addition of P to A lengthened Cl 71 ± 71 ms (p<.001) SACT 9 ± 10 ms (p<.01) and CSNRT 33 ± 51 ms (p<.05). In 60H, addition of P to A lengthened Cl 71 ± 31 ms (p<.001) and CSNRT 27 ± 36 ms (p<.01). Change in SACT was N.S.We conclude: (1) SAN function responds to beta blockade with and without chemical sympathectomy. (2) SAN automaticity following vagal blockade appears to decrease with age. This relationship is abolished by sympathectomy, and may be due to developing cardiac sympathetic innervation.

The effect of atropine on heart rate and oxygen consumption of the hypoxic fetus

To determine if vagal blockade during hypoxic bradycardia improves fetal oxygenation, 10 studies were carried out on five chronically instrumented sheep after 0.8 week of gestation. At a mean maternal arterial oxygen tension of 33 ± 4 mm Hg, the fetal heart rate decreased 20% to 137 ± 19 bpm, and fetal oxygen consumption decreased 42% to 4.6 ± 1.5 ml/min/kg of fetus. After 200 μg atropine was infused into a fetal vein, fetal heart rate increased immediately to 249 ± 26 bpm. Fetal oxygen consumption was unchanged. Fetal heart rate increased by 18 bpm after atropine in the normoxic fetus. These studies show that there is a substantial bradycardia due to an increase in vagal activity during hypoxia in the fetus and that blockade of this activity causes a marked tachycardia but no increase in fetal oxygen uptake.

Neural control of periodic secretion of the pancreas and the stomach in fasting dogs.

The role of nerves in periodic secretion of the pancreas and the stomach in relation to the motility of the upper gastrointestinal tract was studied in conscious fasting dogs which had previously been provided with chronic gastric and pancreatic fistulae and a Heidenhain pouch. Both atropine and pentolinium abolished the periodic increase in gastric and pancreatic secretion and motility of the gut. Bilateral cervical vagal blockade with lidocaine reduced the motility of the stomach, the duodenum and the pouch preceding their peaks, but the motility at the peaks remained unchanged except in the case of the stomach. Pancreatic secretion preceding its peak was also decreased by vagal blockade but that at the peak was not significantly different from the control peak. Periodic pepsin secretion, from both the fistula and pouch, was decreased by vagal blockade. It is concluded that the secretion and motility of the upper gut in fasting dogs is controlled by periodic activity of the vagus and intrinsic nerves.

Vagal control of migrating motor complex-related peaks in canine plasma motilin, pancreatic polypeptide, and gastrin.

The role of the vagus nerve in the control of fasting plasma pancreatic polypeptide (PP), gastrin, and motilin levels was investigated in conscious dogs. Lowest plasma levels of motilin (81 +/- 8 pmol/L), PP (19 +/- 1 pmol/L) and gastrin (5 +/- 1 pmol/L) were observed during phase I of the migrating motor complex (MMC). Significant peaks in plasma motilin (127 +/- 11 pmol/L, P less than 0.005), PP (26 +/- 2 pmol/L, P less than 0.005), and gastrin (14 +/- 2 pmol/L, P less than 0.005) were seen, coinciding with the appearance of phase II (PP and gastrin) or phase III (motilin) of the migrating motor complex in the upper gut. Whereas bilateral vagal blockade abolished the peaks in PP and gastrin, a significant (P less than 0.025) increment in plasma motilin remained, which correlated with the late phase III equivalent of the vagally independent complex (VIC) in the duodenum. This VIC-related motilin peak (170 +/- 20 pmol/L) was significantly higher (P less than 0.025) and the time course (9 +/- 2 min) significantly shorter (P less than 0.01) than the peak (127 +/- 11 pmol/L) and duration (31 +/- 9 min) observed without vagal blockade. Thus, in fasting, the cyclical increments of PP and gastrin are both dependent on excitatory vagal innervation, whereas excitatory pathways controlling phase III associated peak motilin release are nonvagal. In addition, the pattern of fasting motilin release and the amplitude of peak motilin secretion may be affected by vagal inhibition.

Baroreflex control of myocardial contractility in conscious normotensive and renal hypertensive rabbits.

We have assessed resting myocardial contractility and its baroreflex control in normotensive and hypertensive conscious rabbits. Hypertension was induced by bilateral cellophane wrapping of the kidneys with experiments performed 6 weeks later during the established phase of hypertension. The peak rate of change of left ventricular pressure (peak LV dP/dt) was used as the index of myocardial contractility. Baroreflex control of contractility and heart period (HP) was assessed by constructing stimulus response curves relating change in mean arterial pressure (MAP), induced by balloon occluders around the abdominal aorta and inferior vena cava, to change in peak LV dP/dt and HP. These stimulus response curves were obtained in normotensive rabbits with and without cardiac pacing, and in both normotensive and hypertensive animals after cardiac beta sympathetic blockade with propranolol, vagal blockade with methylscopolamine, and combined cardiac autonomic blockade with propranolol and scopolamine, as well as in rabbits with intact autonomic effectors. Resting MAP was significantly higher in the hypertensive rabbits (119 +/- 2 mm Hg) compared to normotensive controls (76 +/- 1 mm Hg). Resting peak LV dP/dt was also greater by 51% in the hypertensive animals (7054 +/- 287 mm Hg sec-1) compared to controls (4690 +/- 223 mm Hg sec-1). There was no significant difference in the resting heart period or resting left ventricular end diastolic pressure. Transient changes in MAP induced by occlusion of the aortic or venous balloons produced significant alterations in peak LV dP/dt in normotensive animals with and without pacing and in hypertensive control animals. In animals with cardiac sympathetic block, the range and slope or sensitivity of the stimulus response curves were not significantly changed but in animals with vagal blockade the sensitivity was reduced by 90% and the range at 30 mm Hg by 88%. After propranolol and methylscopolamine were administered together, the stimulus no longer evoked a response. These experiments demonstrate that myocardial contractility is under baroreflex control and suggest that this is mediated principally via parasympathetic nerves to the heart. There was no significant difference between the sensitivity of baroreflex control of myocardial contractility in the normotensive (-84 +/- 14 mm Hg sec-1 per mm Hg) and the hypertensive (-110 +/- 14 mm Hg sec-1 per mm Hg) rabbits, unlike the baroreflex control of heart period where sensitivity was markedly impaired in the hypertensive (sensitivity 3.8 +/- 0.8 msec/mm Hg) compared to the normotensive (6.9 +/- 1.0 msec/mm Hg) animals.

The response of the pancreas of the anaesthetized cat to secretin before, during and after reversible vagal blockade.

Cooling the cervical vagi of the anaesthetized splanchnectomized cat to 2 degrees C caused a 54.4 +/- 8.8% inhibition of pancreatic electrolyte secretion stimulated submaximally with pure secretin. On rewarming the vagi there was a prolonged increase in secretion rate over and above the control rate which existed before cooling. The increase lasted about 90 min. There were no changes in acid/base status due to interference of the lung inflation reflex which could account for the inhibition of secretion and the subsequent rebound. Cold block of the cervical vagi increased the transpancreatic electrical conductance, indicating that vasodilation had occurred and therefore eliminated a vasomotor cause for the inhibition. Electrolyte secretion was also inhibited by bilateral vagal section. Atropine only partially prevented the inhibitory response to vagal cooling. A cholinergic mechanism, therefore, accounted for some but not all of the response to vagal cooling. It is concluded that even in the fasted, anaesthetized animal vagal impulses facilitate the action of secretin on the pancreas. This facilitation is only partially cholinergic; the major part of the response is due to some non-cholinergic transmitter substance. Such a mechanism may be necessary to potentiate the action of the very small amounts of secretin which appear to be released during a meal.

Mu-receptors mediate opioid cardiovascular effects at anterior hypothalamic sites through sympatho-adrenomedullary and parasympathetic pathways.

Intracerebroventricular injections of selective opioid agonists were used to investigate the role of opiate receptor subtypes in cardiovascular function in awake rats. The mu-agonist (D-Ala2,MePhe4,Gly5-ol)enkephalin (1 nmol) caused a prolonged increase in blood pressure and an initial decrease followed by a delayed increase in heart rate. These effects were antagonized by the selective mu-antagonist beta-funaltrexamine. A selective delta-agonist (dimeric tetrapeptide enkephalin) was devoid of cardiovascular effects at 10 nmol, whereas a benzomorphan kappa-agonist MRZ caused a pressor response which was not antagonized by beta-funaltrexamine. The mechanisms by which opioids elicit cardiovascular effects were analyzed in detail by using microinjections into the anterior hypothalamic area. Low doses of enkephalin produced increases in heart rate and blood pressure. Associated elevations of plasma norepinephrine and epinephrine, but not vasopressin, suggested a stimulation of sympatho-adrenomedullary pathways. Higher doses caused increases in blood pressure but decreases in heart rate. Peripheral vagal blockade with atropine methyl nitrate caused a large sudden rise in heart rate, indicating that an increased vagal outflow counteracted the sympathetic activation. Adrenal demedullated rats displayed no tachycardia after anterior hypothalamic injection of low doses of enkephalin, whereas high dose caused pronounced bradycardia. Additional treatment of demedullated rats with the sympathetic blocker bretylium led to severe hypotension in addition to bradycardia. These data provide evidence that mu-opiate receptors primarily mediate cardiovascular effects of opiates in awake rats. At low doses, a sympathetic adrenomedullary activation occurs, whereas higher doses additionally activate parasympathetic efferents, both possibly from anterior hypothalamic sites.

Effect of pancreatic polypeptide on canine migrating motor complex and plasma motilin.

A potential role of pancreatic polypeptide (PP) in the regulation of phase III of the migrating motor complex (MMC) was investigated in conscious dogs before and during bilateral vagal blockade. After a control fasting period, cyclical increments in plasma PP occurred with peak levels of 45 +/- 8 pmol/l coinciding with late phase II MMC motility. By contrast, after food a substantially higher (approximately five times peak fasting concentrations) and more prolonged elevation of PP was observed, in association with a postprandial pattern of activity. To approximate fasting plasma PP concentrations, porcine PP was infused at 100 pmol X kg-1 X h-1, which produced levels of plasma PP of 99 +/- 8 pmol/l. At this dose PP had no effect on phase III activity. However, at a dose of 400 pmol X kg-1 X h-1, which achieved plasma PP concentrations (283 +/- 33 pmol/l) similar to postprandial levels, there was a specific inhibition of phase III in the lower esophageal sphincter, stomach, duodenum, and upper jejunum. The phase III-associated increment of plasma motilin was also inhibited by this dose of PP. These inhibitory effects at the 400 pmol X kg-1 X h-1 dose of PP were also observed after bilateral blockade of the vagus nerves. Our results suggest that PP has no significant role in the modulation of phase III of the fasting MMC nor does it induce a typical feeding motor pattern. The selective inhibition of both phase III and the associated rise in plasma motilin by PP plasma levels similar to postprandial concentrations does, however, point to a possible role for pancreatic polypeptide in the postprandial inhibition of phase III of the MMC.

Effect of graded vagal blockade and pulmonary volume on tonic inspiratory activity in rabbits.

Reflex respiratory responses to increased and decreased tracheal pressure have been studied at bilateral local vagus temperatures between 30 degrees C and 0 degrees C in anaesthetized spontaneously breathing rabbits. The temperature of each cervical vagus nerve was governed by separate thermodes, which were cooled by Peltier elements and heated by transistors. In this study, the lowest activity level of the diaphragm during expiration was considered to reflect tonic inspiratory activity. As an indicator for this level, the longest interspike interval in the electromyogram of the diaphragm during a breath was used. Tonic inspiratory activity at tracheal pressures below -1.2 kPa was higher with vagi intact than after vagotomy. This observation indicates that disinhibition, due to the decreased activity of pulmonary stretch receptors, occurring during the Hering-Breuer deflation reflex, is an insufficient explanation for the facilitation of tonic inspiratory activity. When local vagus temperatures are 8 degrees C, and tracheal pressure has been increased or decreased, tonic inspiratory activity is higher than it would be with vagi at 0 degrees C or cut. Two reflex mechanisms that might explain the observed high tonic inspiratory activity are discussed.

Carotid chemoreceptor regulation of expiratory duration.

We studied the effect of an experimentally augmented breath on the duration of expiration (TE) to test the hypothesis that within-breath reductions in alveolar partial pressure of CO2 (PACO2) delay the onset of the subsequent inspiration through a carotid chemoreceptor mechanism. Studies were performed in five carotid body intact (CBI) and three carotid body denervated (CBD) dogs during quiet wakefulness and nonrapid-eye-movement sleep. The vagus nerves were blocked in order to abolish vagal mechanisms capable of modulating TE. In CBI dogs, mechanically augmented breaths [mean tidal volume (VT), 149% of control] induced a mean decrease in PACO2 of 3.3 Torr and prolonged TE by 2.21 s to 127% of control (P less than 0.001). In contrast, in CBD dogs augmented breaths of comparable magnitude failed to change TE. Spontaneous sighs in fully intact dogs (mean VT, 369% of control) produced marked prolongation of TE (to 429% of control). In CBI dogs, there was a direct relationship between VT and the resulting TE across all experimental conditions (control, vagal blockade, augmented breaths, spontaneous sighs), whereas in CBD dogs, changes in VT failed to alter TE. The results indicate that the carotid bodies are able to induce within-breath alterations in TE and that such a mechanism can account for the prolongation of TE by vagal blockade and by spontaneous sighs.

Is there a serotonin-induced hypertensive coronary chemoreflex in the nonhuman primate?

The purpose of this study was to investigate the nature of the serotonin-induced coronary chemoreflex in the conscious monkey. Ten chronically prepared and four acute monkeys were used in this study. Five chronically prepared animals had catheters in the left atrium, ascending aorta, descending aorta, and, bilaterally, in the common carotid arteries. In addition, Silastic catheters were placed next to both vagi to permit vagal block with 2% lidocaine. Serotonin was injected (12-200 micrograms/kg) into the left atrium, ascending aorta, descending aorta, or, bilaterally, into the carotid arteries while blood pressure, heart rate, and respiratory movements were recorded. Injections of serotonin were associated with hypertension and bradycardia followed by tachycardia, all of which were preceded by a cough response. Atropine blocked the bradycardia, whereas atropine and phentolamine eliminated the cardiovascular components of the reflex. Vagal blockade eliminated the bradycardia but otherwise did not alter the response to left atrial serotonin. Three monkeys were prepared with aortic and left atrial catheters. Subsequently, they were subjected to sinoaortic deafferentation. Serotonin injected into these animals did not alter blood pressure or respiration. The results of this study show that serotonin injected into the left atrium of the conscious monkey produces respiratory and cardiovascular alterations by its effect on aortic and carotid chemoreceptors, and that there is no coronary chemoreflex in the conscious monkey.