Reflex co-ordination of corporal and antral contractions in the conscious dog.

This study characterizes the role of extrinsic nerves in the co-ordination of corporal and antral contractions in the dog. Fasting motor activity was recorded in conscious dogs with stomachs previously divided into separate corporal and antral pouches. Both corpus and antrum showed synchronized phases of activity and quiescence recognizable as migrating motor complexes (MMCs, duration 81.2 +/- 9.6 min, n = 4). Moreover, individual contractions were temporally linked such that corpus contractions, occurring at 76 +/- 4 s intervals, were each followed by a burst of one to three antral contractions at a frequency of 4-5 min-1. The mean latency between the onset of individual contractions in the corpus and antrum was 10.9 +/- 2.6 s (n = 4). Denervation of the antral pouch in two additional dogs did not affect the MMC cycle (mean durations 106.6 and 82.1 min) and the onset of activity in the corpus and antrum was generally co-ordinated but less precise. However, individual antral contractions were no longer linked to corporal contractions, occurring randomly throughout the corpus contraction cycle. This was associated with a lower contraction frequency in the denervated antral pouches than in the corpus (0.3 +/- 0.1 min-1 compared to 0.6 +/- 0.08 min-1). It is proposed that a vagal reflex, excited by corporal tension receptors, provides phasic excitation facilitating the generation of antral contractions. Such a reflex is likely to reinforce the myogenic mechanisms which occur in the intact stomach and thus plays a role in co-ordinating gastric peristalsis.

Pre-pyloric mechanisms regulating gastric motor function in the conscious dog.

Reflex mechanisms regulating gastric motor function were studied in four conscious dogs, whose stomachs had been surgically divided into separate corporal and antral pouches. Interactions between the corpus and antrum were investigated in fasted animals by balloon distension of each region. During the quiescent phase (phase I) of the migrating motor complex (MMC), distending the corpus with volumes greater than 80 ml resulted in contractions of the corpus, which persisted for as long as the distending stimulus was applied. This corporal distension also initiated antral contractions which were greater if the antrum was moderately distended and also greater with a larger corporal distending volume up to 300 ml. Graded 5 ml inflation of the antrum during the quiescent phase of the MMC stimulated antral contractions. This antral response to antral distension was augmented when the corpus was inflated but was only statistically significant with antral volumes below 25 ml. Distension of the antrum with volumes greater than 12.5 ml caused inhibition of corporal contractions during both the active phase of a migrating complex or when stimulated by corporal inflation. The degree of inhibition was proportional to the distending stimulus and was present for the duration of the applied distension. For antral volumes of 50 ml the inhibition persisted for a variable time after the stimulus was withdrawn. The inhibition of corporal activity by antral distension was still effective after blocking acid secretion with cimetidine (100 mg), which would eliminate spillage of acid into the jejunum as a cause of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Space: a testbed for basic biomedical sciences.

In Space many bodily functions adjust to the absence of gravity. Our understanding of these homeostatic processes have depended on studies on man and other animals. The present paper briefly reviews how such studies may benefit some terrestrial medical problems.

Physiological problems for man in space.

This article discusses some of the problems facing man in space. Many of these problems are manifested only on return to Earth when the de-conditioned body again has to withstand the effects of gravity.

Calcium metabolism and the osteopenia of space flight.

This paper briefly reviews the subject of bone remodelling and calcium homeostasis and considers the changes that occur in the microgravity environment of space. The effectiveness of exercise as a countermeasure to bone demineralisation is discussed.

Food for thought--nutritional problems in space.

The present paper discusses how the study of nutritional problems in space have proceeded, the way microgravity may alter nutritional requirements and how these may be met during long term missions in space.

Disruption of the jejunal migrating motor complex by gastric distension and feeding in the dog.

1. The jejunal motor response to gastric distension has been quantified in the conscious dog and compared with that of feeding in order to determine the role of the physical bulk of a meal in the conversion from fasted to fed motor activity. 2. In six dogs gastric distension abolished the cyclical migrating motor complex (m.m.c.) and evoked a pattern of continuous irregular jejunal motility similar to that seen postprandially, but only after a latency of 21.5 +/- 2.7 min compared to that of 7.1 +/- 1.2 min for the response to feeding. Computer analysis of distension and fed jejunal motility revealed similar distributions of intervals between contractions and contraction amplitudes with comparable mean values for both. 3. In two dogs with antrum and corpus surgically divided distension of the corpus had a similar effect on jejunal motility although the latency to both distension and feeding were considerably less. 4. By varying the period of distension it has been possible to control accurately the duration of the jejunal motor response and so assess its effectiveness in disrupting the timing of the m.m.c. The return to m.m.c. cycling following deflation was independent of preceding complexes. The occurrence of the post-distension activity front was closely related to the act of deflation itself (R = 0.94) following a latency of 26.2 +/- 2.1 min (n = 39). 5. It is concluded that the bulk of a meal contributes significantly to the early part of postprandial motility and is capable of disrupting the timing of subsequent migrating motor complexes.

Absence of a relationship between arterial pH and pancreatic bicarbonate secretion in the isolated perfused cat pancreas.

1. The secretion rate of bicarbonate by the isolated saline-perfused cat pancreas was linearly related to the bicarbonate concentration of the arterial inflow at constant PCO2 and at high volume rates of secretion. 2. Pancreatic bicarbonate secretion was independent of arterial inflow pH at constant bicarbonate concentrations when the pH was manipulated by alterations in the PCO2 at high volume rates of secretion. 3. A small but statistically significant linear relationship existed between the pH of the arterial inflow and bicarbonate secretion at constant PCO2 after inhibition of carbonic anhydrase by acetazolamide. Under the same conditions no relationship was found between bicarbonate secretion and arterial inflow pH when the perfusate bicarbonate concentration was kept constant and the PCO2 varied. 4. When the volume rate of secretion was reduced by about 60-70% of maximum no relationship was found to exist between arterial inflow pH and bicarbonate secretion at constant bicarbonate concentration in the perfusate. There was also no relationship between inflow pH and bicarbonate secretion at constant PCO2 down to a pH of 7.3 until the bicarbonate concentration of the perfusate was reduced below 10 mM, when the secretion rate fell off rapidly. 5. A linear relationship was found to exist between the volume rate of secretion and the PCO2 of the pancreatic juice and the output of lactate both in the isolated saline-perfused gland and the blood-perfused pancreas in situ. 6. At high rates of secretion the PCO2 of the pancreatic juice was always higher than that of either the arterial inflow or the venous outflow. There is therefore no gradient for the passive movement of carbon dioxide between the arterial inflow and the pancreatic juice. 7. Inhibition of secretion with acetazolamide caused a fall in the PCO2 of pancreatic juice and increased the output of lactate. The secretion of lactate was not due to hypoxia as it also occurred in the blood-perfused gland in situ which had normal haemoglobin concentrations and oxygen saturation. 8. It is concluded that the secretion of bicarbonate is independent of arterial pH but critically dependent upon the arterial concentration of the bicarbonate ion. These experiments do not support the concept that the secretion of protons over the basolateral membrane is the major primary event in pancreatic secretion of bicarbonate.

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 (less than 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 HCl was the most effective stimulus accounting for 81% of the efferent responses although these were of long-latency (greater than 1 min), gradual in onset and poorly maintained. Other efferent responses to HCl 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.

Vagal afferent discharge from gastric mechanoreceptors during contraction and relaxation of the ferret corpus.

Vagal afferent fibres with mechanoreceptive fields in the gastric corpus were studied electrophysiologically in the urethane-anaesthetized ferret in an attempt to assess how changes in muscle tension and length modulate receptor discharge. Single afferent units were spontaneously active and increased their firing on distension of the corpus. During vagally evoked isovolumetric contractions and relaxations, the afferent discharge closely followed changes in intracorpus pressure. Under near-isotonic conditions, changes in both intracorpus pressure and afferent discharge were attenuated to similar degrees despite large changes in corpus volume, although the latter had a modulating influence on afferent discharge. These mechanoreceptors appeared to behave as tension receptors but were also influenced by muscle length as would occur if the receptor were associated with the laminar intramuscular septa of connective tissue which may serve as intramuscular tendons in this tissue.

A permissive role for the vagus nerves in the genesis of antro-antral reflexes in the anaesthetized ferret.

1. The role of the vagus nerves in the genesis of antro-antral reflexes was investigated in the urethane-anaesthetized, splanchnectomized ferret. 2. Antral distension stimulated antral contractions with a threshold volume of 3.5 +/- 0.9 ml (corresponding to an intra-antral pressure of 0.27 +/- 0.11 kPa) by a vagal-dependent mechanism as indicated by the attenuated response seen during vagal blockade by cooling. Atropine (1 mg/kg) abolished the antral response to distension. 3. In vagotomized animals, close arterial infusions of acetylcholine at a dose sufficient to return antral motility to basal levels led to the reappearance of the reflex. Low-frequency electrical stimulation of the preganglionic vagal neurones had a similar effect. These effects were also abolished by atropine (1 mg/kg). 4. Hexamethonium (10-25 mg/kg) suppressed the potentiating effect of acetylcholine, indicating a ganglionic site of action. The attenuated response to antral distension seen in vagotomized animals in the absence of exogenous acetylcholine or electrical vagal stimulation was not sensitive to hexamethonium but abolished by atropine (1 mg/kg). 5. The results are consistent with the vagus performing a permissive role in the genesis of antro-antral reflexes mediated through local enteric pathways.

Evidence for a non-cholinergic excitatory innervation in the control of colonic motility.

The colon of the ferret anesthetized with urethane exhibits two distinct types of motility patterns. These were abolished or considerably reduced by blocking nervous conduction in the vagus nerves by cooling to below 4 degrees C. Atropine transiently abolished motility which on its return was also found to be sensitive to vagal integrity. Electrical stimulation of either the cut central or peripheral end of a branch of the abdominal vagus caused large amplitude contractions of the colon which were not blocked by atropine or by atropine and a combination of alpha- and beta-adrenoceptor blocking agents. These results are consistent with either two separate motor pathways to the colon in the vagus nerve, one cholinergic, the other non-adrenergic, non-cholinergic, or a single pathway with the effects mediated by a primary and a co-transmitter. They also demonstrate that "spontaneous activity" is driven in part by both cholinergic and non-cholinergic mechanisms.

The effect of intraluminal tryptophan and phenylalanine on small intestinal motility in the conscious dog.

The effect of D- and L-isomers of tryptophan and phenylalanine on fasting motor activity of canine jejunum were investigated. Only L-tryptophan had any effect on jejunal motility. The concentration of L-tryptophan required to elicit a motor effect in 50% of animals was estimated at 28 mM. 50 mM-L-tryptophan stimulated jejunal motility after a latency of 4.5 +/- 0.7 min. The pattern of motility was similar to that evoked by feeding but continued for only 41 +/- 5 min and failed to disrupt the normal timing of the interdigestive migrating motor complex (m.m.c.). The duration of the subsequent phase II of the complex was, however, significantly reduced. Multiple infusion of L-tryptophan also failed to disrupt the timing of the m.m.c. These data are consistent with the hypothesis that specific breakdown components of protein digestion are implicated in the stimulation of postprandial motor activity. The mechanisms involved in the motor response to L-tryptophan are discussed.

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.

The direct inhibition of pancreatic electrolyte secretion by noradrenaline in the isolated perfused cat pancreas.

The continuous infusion of noradrenaline into the arterial supply of the isolated saline-perfused pancreas caused a dose-dependent rise in perfusion pressure, a reduction in perfusion rate and an inhibition of pancreatic secretion. With increasing dose there was always a greater reduction in secretion rate than there was of perfusate flow rate. Manual reduction of the perfusion rate resulted in a reduction in secretion rate. When noradrenaline reduced the perfusate flow by 44.2 +/- 6.0% the secretion rate fell by 76.6 +/- 14.1%. Manual reduction of the perfusion flow rate by a similar amount (43.0 +/- 5.7%) only reduced the secretion rate by 41.4 +/- 7.0%. The infusion of noradrenaline, when all calcium had been removed from the perfusate, caused only a small increase in perfusion pressure with little change in the perfusion flow whilst at the same time the inhibition of electrolyte secretion was relatively unaffected. The vasomotor and secretory effects of noradrenaline were abolished by phentolamine. It is concluded that noradrenaline inhibits pancreatic electrolyte secretion by a direct action on the secretory cell and indirectly by vasoconstriction and that both these effects are mediated through the alpha-receptor.

Vagal control of colonic motility in the anaesthetized ferret: evidence for a non-cholinergic excitatory innervation.

Spontaneous colonic motility in the urethane-anaesthetized ferret consists of two distinct types of contraction which correspond to the patterns recorded myoelectrically in conscious animals. This motility was abolished or greatly reduced when nervous conduction was prevented in the cervical vagi by cooling to below 4 degrees C. On rewarming the nerves the colonic motility returned, after a short latency, to the pre-cool level. Atropine transiently abolished colonic motility. On its return the motility was significantly reduced but still sensitive to vagal integrity. Thus the atropine-resistant colonic motility was also abolished or markedly reduced by cooling the cervical vagi to below 4 degrees C. On rewarming there was a longer latency for the return of motility compared to that before atropinization. Electrical vagal stimulation produced, after a short latency, large-amplitude colonic contractions. Following atropine, the short-latency response to electrical vagal stimulation was replaced in the majority of animals by a long-latency response whose characteristics were quite different from those of the cholinergic response. These results are consistent with the vagus containing two functional motor pathways to the colon, one to cholinergic post-ganglionic neurones and the other operating via a non-cholinergic mechanism.

Vagal influences on the jejunal 'minute rhythm' in the anaesthetized ferret.

Spontaneous jejunal motility in the urethane-anaesthetized ferret shows a cyclical pattern of contraction bursts alternating with quiescent periods described as 'minute rhythm' in conscious animals. Cooling the cervical vagi to below 4 degrees C or acute vagotomy abolished this pattern of motility. On re-warming the vagi there was a return to cyclical motility after a latency which depended upon the contractile state at the time vagal conduction was restored. Electrical vagal stimulation produced bursts of contractions at the same frequency as the spontaneous motility. Longer periods of stimulation gave rise to bursts of contractions interrupted by periods of relative quiescence, mimicking the spontaneous motility, despite the continuous stimulation. Following atropinization all spontaneous motility was abolished, but electrical stimulation of the vagi revealed a non-cholinergic, non-adrenergic response whose characteristics differed from that of the cholinergic response. It is concluded that the vagus plays a permissive role in regulating the jejunal 'minute rhythm' via a cholinergic pathway and that there is a second excitatory vagal pathway which innervates non-cholinergic post-ganglionic neurones whose functional significance and transmitter mechanism is unknown.

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.

Effect of stimulation of the vagus nerve in bursts on gastric acid secretion and motility in the anaesthetized ferret.

1. The effect of electrical stimulation of the vagus nerve with different patterns of impulses (the total number of stimuli remaining constant) on gastric acid secretion and gastric motility were investigated in the anaesthetized ferret. Three stimulus patterns were used: continuous, bursts at ten times the continuous frequency but for a tenth of the time, and a natural burst pattern obtained from a recording of vagal efferent fibre discharge. 2. The natural burst pattern gave rise to gastric contractions of larger amplitude than either the artificial burst or continuous stimulation, while continuous stimulation gave rise to larger changes in tonus. Acid secretion, however, was reduced by the natural pattern of stimulation as compared to the output during continuous stimulation, but to a lesser extent than that due to artificial burst stimulation. 3. Burst stimulation at 10 impulses/sec resulted in a larger output of acid and greater amplitude of gastric contraction than the equivalent continuous stimulation. This potentiation was lost at stimulation frequencies above 30 impulses/sec. 4. At burst frequencies of 60 and 120 impulses/sec there was a marked reduction in acid output and amplitude of contraction as compared with continuous stimulation at 6 and 12 impulses/sec respectively. 5. These results are discussed in relation to the functional significance of the different patterns of vagal discharge seen in the anaesthetized ferret.