scholarly journals Reflex cardiorespiratory events from esophageal origin are heightened by preterm birth

2017 ◽  
Vol 123 (2) ◽  
pp. 489-497 ◽  
Author(s):  
Stéphanie Nault ◽  
Nathalie Samson ◽  
Charlène Nadeau ◽  
Djamal Djeddi ◽  
Jean-Paul Praud

The involvement of gastroesophageal refluxes in cardiorespiratory events of preterm infants remains controversial. While a few studies in full-term newborn animals have shown that stimulation of esophageal receptors leads to cardiorespiratory reflexes, the latter remain largely unknown, especially after premature birth. The present study aimed to 1) characterize the cardiorespiratory reflexes originating from esophageal receptors in newborn lambs and 2) test the hypotheses that preterm birth enhances reflex cardiorespiratory inhibition and that C-fibers are involved in these reflexes. Eight full-term lambs and 10 lambs born 14 days prematurely were studied. Following surgical instrumentation, a 6-h polysomnography was performed without sedation to record electrocardiogram, respiratory movements, arterial pressure, laryngeal constrictor muscle activity, state of alertness, and hemoglobin oxygen saturation. Five esophageal stimulations of the upper and/or lower esophagus, including rapid balloon inflation and/or HCl injection, were performed in random order. A second recording was performed in full-term lambs 24 h later, after C-fiber blockade by capsaicin. Results confirmed that esophageal stimulations induced inhibitory cardiorespiratory reflexes combined with protective mechanisms, including laryngeal closure, swallowing, coughing, increased arterial pressure, and arousal. Preterm birth heightened cardiorespiratory inhibition. The strongest cardiorespiratory inhibition was observed following simultaneous stimulation of the lower and upper esophagus. Finally, cardiorespiratory inhibition was decreased after C-fiber blockade. In conclusion, esophageal stimulation induces inhibitory cardiorespiratory reflexes, which are partly mediated by C-fibers and more pronounced in preterm lambs. Clinical relevance of these findings requires further studies, especially in conditions associated with increased cardiorespiratory events, e.g., neonatal infection. NEW & NOTEWORTHY Preterm birth heightens the cardiorespiratory events triggered by esophageal stimulation. The most extensive cardiorespiratory events are induced by simultaneous stimulation of the proximal and distal esophagus.

1994 ◽  
Vol 267 (6) ◽  
pp. H2398-H2406 ◽  
Author(s):  
H. L. Pan ◽  
G. L. Stahl ◽  
S. V. Rendig ◽  
O. A. Carretero ◽  
J. C. Longhurst

Abdominal ischemia and reperfusion reflexly activate the cardiovascular system. In the present study, we evaluated the role of endogenously produced bradykinin (BK) in the stimulation of ischemically sensitive visceral afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 5 min of abdominal ischemia. Abdominal ischemia increased the portal venous plasma BK level from 49 +/- 10 to 188 +/- 66 pg/ml (P < 0.05). Injection of BK (1 microgram/kg ia) into the descending aorta significantly increased impulse activity (0.88 +/- 0.16 impulses/s) of 10 C fibers, whereas a kinin B1-receptor agonist, des-Arg9-BK (1 microgram/kg), did not alter the discharge rate. Inhibition of kininase II activity with captopril (4 mg/kg i.v.) potentiated impulse activity of 14 ischemically sensitive C fibers (0.44 +/- 0.09 vs. precaptopril, 0.33 +/- 0.08 impulses/s; P < 0.05). In addition, a kinin B2-receptor antagonist (NPC-17731; 40 micrograms/kg i.v.) attenuated activity of afferents during ischemia (0.39 +/- 0.08 vs. pre-NPC-17731, 0.72 +/- 0.13 impulses/s; P < 0.05) and eliminated the response of 10 C fibers to BK. Another kinin B2-receptor antagonist, Hoe-140 (30 micrograms/kg iv), had similar inhibitory effects on six other ischemically sensitive C fibers. In 15 separate cats treated with aspirin (50 mg/kg i.v.), Hoe-140 (30 micrograms/kg i.v.) attenuated impulse activity of only 3 of 16 ischemically sensitive C fibers. These data suggest that BK produced during abdominal ischemia contributes to the stimulation of ischemically sensitive visceral C fiber afferents through kinin B2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


1985 ◽  
Vol 58 (3) ◽  
pp. 907-910 ◽  
Author(s):  
H. D. Schultz ◽  
A. M. Roberts ◽  
C. Bratcher ◽  
H. M. Coleridge ◽  
J. C. Coleridge ◽  
...  

Stimulation of bronchial C-fibers evokes a reflex increase in secretion by tracheal submucosal glands, but the influence of pulmonary C-fibers on tracheal gland secretion is uncertain. In anesthetized dogs with open chests, we sprayed powdered tantalum on the exposed mucosa of a segment of the upper trachea to measure the rate of secretion by submucosal glands. Secretions from the gland ducts caused elevations (hillocks) in the tantalum layer. We counted hillocks at 10-s intervals for 60 s before and 60 s after we injected capsaicin (10–20 micrograms/kg) into the right atrium to stimulate pulmonary C-fiber endings. Right atrial injection of capsaicin increased the rate of hillock formation fourfold, but left atrial injection had no significant effect. The response was abolished by cutting the vagus nerves or cooling them to 0 degree C. We conclude that the reflex increase in tracheal submucosal gland secretion evoked by right atrial injection of capsaicin was initiated as capsaicin passed through the pulmonary vascular bed, and hence that pulmonary C-fibers, like bronchial C-fibers, reflexly increase airway secretion.


1998 ◽  
Vol 84 (1) ◽  
pp. 30-36 ◽  
Author(s):  
C. J. Lai ◽  
Y. R. Kou

Lai, C. J., and Y. R. Kou. Stimulation of vagal pulmonary C fibers by inhaled wood smoke in rats. J. Appl. Physiol. 84(1): 30–36, 1998.—This study investigated the stimulation of vagal pulmonary C fibers (PCs) by wood smoke. We recorded impulses from PCs in 58 anesthetized, open-chest, and artificially ventilated rats and delivered 6 ml of wood smoke into the lungs. Within 1 or 2 s after the smoke delivery, an intense and nonphasic burst of discharge [Δ = +7.4 ± 0.7 (SE) impulses/s, n = 68] was evoked in 60 of the 68 PCs studied and lasted for 4–8 s. This immediate stimulation was usually followed by a delayed and more sustained increase in C-fiber activity (Δ = +2.0 ± 0.4 impulses/s). The overall stimulation was not influenced by removal of smoke particulates ( n = 15) or by pretreatment with vehicle ( n = 8) for dimethylthiourea (DMTU; a hydroxyl radical scavenger) or indomethacin (Indo; a cyclooxygenase inhibitor). The immediate-phase stimulation was not affected by pretreatment with Indo ( n= 8) but was largely attenuated by pretreatment with DMTU ( n = 12) or by a combined treatment with DMTU and Indo (DMTU+Indo; n = 8). Conversely, the delayed-phase stimulation was partially suppressed either by DMTU or by Indo but was totally abolished by DMTU+Indo. These results suggest that 1) the stimulation of PCs is linked to the gas phase of wood smoke and 2) hydroxyl radical, but not cyclooxygenase products, is involved in the immediate-phase stimulation, whereas both metabolites are responsible for evoking the delayed-phase stimulation.


1985 ◽  
Vol 59 (5) ◽  
pp. 1487-1494 ◽  
Author(s):  
J. R. Coast ◽  
S. S. Cassidy

It has been suggested that pulmonary C-fiber stimulation is responsible for the rapid shallow breathing that accompanies pulmonary edema. However, pulmonary C-fiber stimulation also causes apnea. To determine whether it was possible for both responses to occur from one stimulus, we infused varying concentrations of capsaicin (a compound that selectively stimulates C-fiber receptors in the dog) into an in situ vascularly isolated dog lung and measured rates and strengths of diaphragmatic contractions with a strain gauge sutured to the diaphragm and electromyogram electrodes implanted in the diaphragm. There was a dose response to capsaicin in that increased doses were related directly with the duration of cessation of diaphragmatic contractions (2–100 s) and inversely with the latency from the start of stimulation to the beginning of the cessation of diaphragmatic contractions (100–5 s). There was no evidence, however, of rapid shallow breathing in this set of experiments. Either a gradual return to normal rate from prolonged contraction intervals or no change in contraction rate was seen, depending on capsaicin concentration. We conclude that the primary diaphragmatic response to pulmonary C-fiber stimulation is a cessation of diaphragmatic contractions rather than rapid shallow contractions.


1985 ◽  
Vol 59 (4) ◽  
pp. 1085-1089 ◽  
Author(s):  
M. P. Kaufman ◽  
G. A. Ordway ◽  
T. G. Waldrop

Although positive end-expiratory pressure (PEEP) is believed to depress cardiac output and arterial pressure by compressing the vena cava and the heart, it is unclear whether PEEP also depresses these variables by a reflex arising from an inflation-induced stimulation of pulmonary C-fibers. We therefore recorded the impulse activity of 17 pulmonary C-fibers in barbiturate-anesthetized dogs with closed chests, while we placed the expiratory outlet of a ventilator under 5–30 cmH2O. Increasing PEEP in a ramp-like manner stimulated 12 of the 17 pulmonary C-fibers, with activity increasing from 0.0 +/- 0.1 to 0.9 +/- 0.2 imp/s when end-expiratory pressure equaled 15 cmH2O. When PEEP was increased in a stepwise manner to 15–20 cmH2O and maintained at this pressure for 15 min, pulmonary C-fibers increased their firing rates, but the effect was small averaging 0.2–0.3 imp/s after the 1st min of this maneuver. We conclude that pulmonary C-fibers are unlikely to be responsible for causing much of the decreases in cardiac output and arterial pressure evoked by sustained periods of PEEP in both patients and laboratory animals. These C-fibers, however, are likely to be responsible for causing the reflex decreases in these variables evoked by sudden application of PEEP.


2016 ◽  
Vol 310 (3) ◽  
pp. G215-G223 ◽  
Author(s):  
M. Brozmanova ◽  
L. Mazurova ◽  
F. Ru ◽  
M. Tatar ◽  
Y. Hu ◽  
...  

Clinical studies indicate that adenosine contributes to esophageal mechanical hypersensitivity in some patients with pain originating in the esophagus. We have previously reported that the esophageal vagal nodose C fibers express the adenosine A2Areceptor. Here we addressed the hypothesis that stimulation of the adenosine A2Areceptor induces mechanical sensitization of esophageal C fibers by a mechanism involving transient receptor potential A1 (TRPA1). Extracellular single fiber recordings of activity originating in C-fiber terminals were made in the ex vivo vagally innervated guinea pig esophagus. The adenosine A2Areceptor-selective agonist CGS21680 induced robust, reversible sensitization of the response to esophageal distention (10–60 mmHg) in a concentration-dependent fashion (1–100 nM). At the half-maximally effective concentration (EC50: ≈3 nM), CGS21680 induced an approximately twofold increase in the mechanical response without causing an overt activation. This sensitization was abolished by the selective A2Aantagonist SCH58261. The adenylyl cyclase activator forskolin mimicked while the nonselective protein kinase inhibitor H89 inhibited mechanical sensitization by CGS21680. CGS21680 did not enhance the response to the purinergic P2X receptor agonist α,β-methylene-ATP, indicating that CGS21680 does not nonspecifically sensitize to all stimuli. Mechanical sensitization by CGS21680 was abolished by pretreatment with two structurally different TRPA1 antagonists AP18 and HC030031 . Single cell RT-PCR and whole cell patch-clamp studies in isolated esophagus-specific nodose neurons revealed the expression of TRPA1 in A2A-positive C-fiber neurons and demonstrated that CGS21682 potentiated TRPA1 currents evoked by allylisothiocyanate. We conclude that stimulation of the adenosine A2Areceptor induces mechanical sensitization of nodose C fibers by a mechanism sensitive to TRPA1 antagonists indicating the involvement of TRPA1.


2003 ◽  
Vol 94 (5) ◽  
pp. 1978-1986 ◽  
Author(s):  
Julie Arsenault ◽  
François Moreau-Bussière ◽  
Philippe Reix ◽  
Théophile Niyonsenga ◽  
Jean-Paul Praud

The postnatal development of ventilatory reflexes originating from bronchopulmonary receptors was assessed in preterm vs. full-term lambs. Ventilation and arterial pressure were repeatedly measured in 10 preterm (gestational age, 132 days) and 7 full-term lambs without sedation from day 1 to day 42. The Hering-Breuer inhibitory reflex (slowly adapting stretch receptors) was assessed by the increase in expiratory time during end-inspiratory occlusion. The pulmonary chemoreflex (C-fiber endings) was assessed by the initial apnea + bradycardia + systemic hypotension and the secondary tachypnea after capsaicin intravenous injection. Results show the following. 1) Premature birth did not modify the maturation of the Hering-Breuer reflex. 2) Whereas a classic pulmonary chemoreflex was observed in the very first hours of life in preterm lambs, the tachypneic component of this reflex was weaker than in full-term lambs on day 1. 3) Premature birth led to a reversed postnatal maturation of this tachypneic response (tendency to increase with postnatal age). Our findings suggest that premature birth in lambs modifies postnatal maturation of the pulmonary chemoreflex.


1978 ◽  
Vol 41 (6) ◽  
pp. 1592-1613 ◽  
Author(s):  
W. K. Dong ◽  
H. Ryu ◽  
I. H. Wagman

1. An extracellular study of the cat medial thalamus has revealed four types of somatosensory neurons. These were located primarily in the n. parafascicularis, n. subparafascicularis, and n. centralis lateralis; none were found in the n. centrum medianum. There was no functional segregation of neurons within each nucleus or between nuclei. Each type of neuron had large and often bilateral receptive areas. No somatotopic organization of neurons was found within the medial thalamus. 2. Noxious (N) and noxious-tap (NT) neurons comprising 72% of the sample (78 of 109 total) were considered to be nociceptive. N cells responded exclusively to noxious mechanical stimulation of skin, muscle fascia, tendons, and joints, and to direct stimulation of A-delta- and C-fiber groups in cutaneous, articular, and muscle nerves. NT cells responded to noxious and tap stimulation in a differential manner and to stimulation of the entire spectrum of A- and C-fibers. N and NT cells accurately signaled the duration of noxious mechanical stimulation. Their nociceptive responses were also graded as a function of both noxious stimulus intensity and the number of activated A-delta- and C-fibers. Stimulation of A- and C-fibers evoked, respectively, an inital burst and a late burst of discharges. A brief period of inhibition intervened between the initial and late bursts of NT cells. Prolonged afterdischarge was often observed following noxious natural stimulation or stimulation of A-delta- and C-fibers. The phenomenon of discharge "windup" was observed during iterative stimulation of C-fibers. 3. Tap (T) neurons (10%) responded only to brisk but innocuous taps applied to skin or underlying tissue. These cells were driven only by activation of A-alpha- and A-beta-fibers. The response to such stimulation was seen as an initial burst of discharges followed by an inhibitory period. 4. Inhibited (I) neurons (18%) had resting discharges that were inhibited by noxious stimuli and stimulation of A-beta- and C-fiber groups. 5. The results obtained from monitoring the peripherally evoked responses of nociceptive N and NT neurons before and after selective lesions of the spinal cord strongly suggested that the spinothalamic tracts were the only spinal projections mediating A- and C-fiber input to these cells. Each spinothalamic tract apparently carried information originating from both sides of the body.


1988 ◽  
Vol 68 (2) ◽  
pp. 279-283 ◽  
Author(s):  
Bengt H. Sjölund

✓ Transcutaneous electrical nerve stimulation (TENS) is an acknowledged clinical technique to alleviate chronic pain. Its effectiveness is still limited, however, and the stimulation parameters used are based on subjective reports from patients. In the present study, the systematic investigation of conditioning stimulation that was previously reported by the author has been extended to include short trains of stimuli at a low repetition rate (0.1 to 5 Hz) delivered to dissected skin and muscle nerves in the lightly anesthetized rat. The size of a C-fiber-evoked flexion reflex was utilized as a measure of transmission from nociceptive afferentnerve fibers in the spinal cord and was tested repeatedly after 30 minutes of conditioning TENS-like stimulation to adjacent nerves. At these low rates, stimulation of a muscle nerve was usually more effective in suppressing transmission from C-fibers to second-order neurons than was stimulation of a skin nerve. Furthermore, a stimulation strength recruiting both Group I–II and III muscle afferent fibers was more effective in depressing the C-fiber-evoked activity at all frequencies studied than was that activating Group I–II fibers only. A pulsetrain repetition rate of around 1 Hz was most effective. These findings should be taken into account when carrying out clinical TENS treatment.


1984 ◽  
Vol 247 (3) ◽  
pp. R552-R559 ◽  
Author(s):  
J. C. Longhurst ◽  
M. P. Kaufman ◽  
G. A. Ordway ◽  
T. I. Musch

Stimulation of sensory endings in abdominal visceral organs with capsaicin or bradykinin reflexly increases heart rate, blood pressure, and myocardial contractility through afferent pathways in splanchnic nerves. To determine the afferent fiber types stimulated, we recorded impulses in the right splanchnic nerve in 12 anesthetized cats after either injecting capsaicin (50-200 micrograms) or bradykinin (6.5-20 micrograms) into the descending thoracic aorta or applying pledgets soaked with these chemicals to a visceral organ. We studied 26 A- and 23 C-fibers, each with one receptive field in the mesentery, stomach, duodenum, jejunum, ileum, pancreas, liver, gallbladder, or porta hepatis. Endings of C-fibers generally were mechanically insensitive, whereas endings of A-fibers were mechanically sensitive. After a latency of 10.7 +/- 3.3 s, capsaicin increased the activity of 10 of 26 A-fibers from 2.0 +/- 0.9 to 9.9 +/- 2.6 impulses/s and 23 of 23 C-fibers from 0.2 +/- 0.1 to 13.0 +/- 1.6 impulses/s after a latency of 3.3 +/- 0.9 s. Bradykinin increased the activity of 15 of 26 A-fibers from 2.6 +/- 0.9 to 7.4 +/- 1.5 impulses/s after a latency of 17.0 +/- 1.7 s and 16 of 22 C-fibers from 0.4 +/- 0.2 to 4.7 +/- 1.2 impulses/s after a latency of 19.0 +/- 1.9 s. Capsaicin stimulated significantly more C- than A-fibers (P less than 0.001) and a significantly greater fraction of C-fibers than did bradykinin (P less than 0.007). We conclude that stimulation of splanchnic C-fiber afferents by capsaicin and both A- and C-fiber afferents by bradykinin is primarily responsible for the reflex cardiovascular responses caused by these chemicals.


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