Acute radiation-induced vomiting in area postrema-ablated cats

A dose-response relationship was established in normal unanesthetized cats for emetic incidence, latency to onset of vomiting, and duration of emetic activity over a period of 24 h after whole-body exposure to 60Co radiation at selected doses between 7.5 and 90 Gy. Each episode of vomiting, i.e., retching and expulsion, was recorded oscillographically as its characteristic intrathoracic pressure waveform by means of a catheter inserted some days before into the superior vena cava. The gamma-radiation dose of 45 Gy evoked vomiting optimally with an incidence of 92% and an average onset time of 98 min. When administered to animals prepared chronically with surgical ablation of the area postrema, the same dose of radiation evoked vomiting in four of five test cases and with an average time to onset that was not by either measure significantly different from normal. Vomiting was also elicited in all of six normal cats exposed to an intestinal dose of 45 Gy X radiation with the head shielded. The same form of irradiation evoked vomiting in two of three chronically postremectomized cats. Successful ablation of the area postrema was determined functionally by emetic refractoriness to an injection of digitalis and confirmed for completeness by histological examination. It is concluded that the area postrema is not an essential element in the reflex mechanism of radiation-induced vomiting and, therefore, no physiological basis exists for dependence on a centrally acting chemogenic factor in radioemesis.     

Digestive tract motor correlates of vomiting and nausea

The digestive tract from the upper esophageal sphincter to the ileum participates in the vomiting process, but the role of the digestive tract in nausea is unclear. In preparation for vomiting, the proximal stomach relaxes and the small intestine is evacuated orad in a single mass movement by a retrograde giant contraction and caudad in a stripping fashion by a series of phasic contractions. Orad evacuation of the small intestine may not only remove offending substances but may also dilute. or buffer gastric contents with intestinal and pancreaticobiliary secretions. In association with retching and vomiting, the striated muscle of the esophagus contracts longitudinally, pulling the relaxed proximal stomach into the thoracic cavity forming a funnel from stomach to esophagus. However, gastric evacuation does not occur until the hiatal fibers of the diaphragm relax during vomitus expulsion. Nausea is a subjective feeling in humans that is difficult to identify in animals. Various changes in digestive tract activity have been associated with nausea, but no evidence suggests that these events cause nausea. The prodromal signs of vomiting (e.g., increased heart rate and respiration) that occur concomitantly with the gastrointestinal motor correlates of vomiting have been considered autonomic indices of nausea in animals, but this has not been proven. Regardless, the gastrointestinal motor correlates of vomiting do not cause the prodromata. The emetic central pattern generator may be organized in parallel with respect to its individual autonomic correlates, but as groups of responses, the autonomic and somatomotor correlates may be organized in series.     

Mechanisms of airway protection during retching,vomiting, and swallowing

We investigated the mechanisms of airway protection and bolus transport during retching and vomiting by recording responses of the pharyngeal, laryngeal, and hyoid muscles and comparing them with responses during swallowing and responses of the gastrointestinal tract. Five dogs were chronically instrumented with electrodes on the striated muscles and strain gauges on smooth muscles. Retching and vomiting were stimulated by apomorphine (5-10 ug/kg iv). During retching, the hyoid and thyroid descending and laryngeal abductor muscles were activated; between retches, the hyoid, thyroid, and pharyngeal elevating, and laryngeal adductor muscles were activated. Vomiting always occurred during the ascending phase of retching and consisted of three sequential phases of hyoid and pharyngeal muscle activation culminating in simultaneous activation of all recorded elevating and descending laryngeal, hyoid, and pharyngeal muscles. Retrograde activation of esophagus and pharyngeal muscles occurred during the later phases, and laryngeal adductor was maximally activated in all phases of the vomit. During swallowing, the laryngeal adductor activation was followed immediately by brief activation of the laryngeal abductor. We concluded that retching functions to mix gastric contents with refluxed intestinal secretions and to impart an orad momentum to the bolus before vomiting. During retches, the airway is protected by glottal closure, and between retches, it is protected by ascent of the larynx and closure of the upper esophageal sphincter. The airway is protected by maximum glottal closure during vomiting. During swallowing, the airway is protected by laryngeal elevation and glottal closure followed by brief opening of the glottis, which may release subglottal pressure expelling material from the laryngeal vestibule.     

Effect of lung volume on the respiratory action of the canine pectoral muscles.

Lung volume influences the mechanical action of the primary inspiratory and expiratory muscles by affecting their precontraction length, alignment with the rib cage, and mechanical coupling to agonistic and antagonistic muscles. We have previously shown that the canine pectoral muscles exert an expiratory action on the rib cage when the forelimbs are at the torso's side and an inspiratory action when the forelimbs are held elevated. To determine the effect of lung volume on intrathoracic pressure changes produced by the canine pectoral muscles, we performed isolated bilateral supramaximal electrical stimulation of the deep pectoral and superficial pectoralis (descending and transverse heads) muscles in 15 adult supine anesthetized dogs during hyperventilation-induced apnea. Lung volume was altered by application of a negative or positive pressure (+/- 30 cmH2O) to the airway. In all animals, selective electrical stimulation of the descending, transverse, and deep pectoral muscles with the forelimbs held elevated produced negative intrathoracic pressure changes (i.e., an inspiratory action). Moreover, with the forelimbs elevated, increasing lung volume decreased both pectoral muscle fiber precontraction length and the negative intrathoracic pressure changes generated by contraction of each of these muscles. Conversely, with the forelimbs along the torso, increasing lung volume lengthened pectoral muscle precontraction length and augmented the positive intrathoracic pressure changes produced by muscle contraction (i.e., an expiratory action). These results indicate that lung volume significantly affects the length of the canine pectoral muscles and their mechanical actions on the rib cage.     

Respiratory muscle control during vomiting

The changes in thoracic and abdominal pressure that generate vomiting are produced by coordinated action of the major respiratory muscles. During vomiting, the diaphragm and external intercostal (inspiratory) muscles co-contract with abdominal (expiratory) muscles in a series of bursts of activity that culminates in expulsion. Internal intercostal (expiratory) muscles contract out of phase with these muscles during retching and are inactive during expulsion. The periesophageal portion of the diaphragm relaxes during expulsion, presumably facilitating rostral movement of gastric contents. Recent studies have begun to examine to what extent medullary respiratory neurons are involved in the control of these muscles during vomiting. Bulbospinal expiratory neurons in the ventral respiratory group caudal to the obex discharge at the appropriate time during (fictive) vomiting to activate either abdominal or internal intercostal motoneurons. The pathways that drive phrenic and external intercostal motoneurons during vomiting have yet to be identified. Most bulbospinal inspiratory neurons in the dorsal and ventral respiratory groups do not have the appropriate response pattern to initiate activation of these motoneurons during (fictive) vomiting. Relaxation of the periesophageal diaphragm during vomiting could be brought about, at least in part, by reduced firing of bulbospinal inspiratory neurons.     

Rhythmic pulses of haemolymph pressure associated with parturition and ovulation in the tsetse fly,Glossina morsitans

Abstract Expulsion of the tsetse larva from the uterus of the female is preceded by 1–2 h of rhythmic pulses of haemolymph pressure that can be detected using a barographic technique. At first baseline pressure is maintained and all pulses are positive in relation to baseline. Then, about 1 h before parturition, baseline pressure increases, pulse intensity increases, and the pulses become both positive and negative in relation to baseline. Each pulse correlates with ‘bobbing’ action of the female's proboscis, the only external indication of this internal activity. A single large pressure pulse is observed at parturition, and thereafter the pressure level returns to the original baseline and pulsing action ceases. Around the presumptive time of ovulation, 1–2 h after parturition, another series of pressure pulses is observed. The pulses are the likely consequence of coordinated waves of muscular contraction that are essential preparation for successful parturition and ovulation.     

Gastric and duodenal motility in the cat: the role of central innervation assessed by transient vagal blockade

Experiments were performed on four cats to characterize fasting gastric and small bowel motility and to assess the role of extrinsic vagal innervation in the control of that motor activity. A multilumen manometry tube was positioned to record pressure changes from the proximal small bowel and stomach. Transient vagal nerve blockade was accomplished by cooling the cervical vagosympathetic nerve trunks, previously isolated in skin loops on each side of the neck. Two characteristic patterns of basal activity were documented in the stomach: (i) regular phasic contractions of variable amplitude in the body of the stomach; and (ii) infrequent, irregular contractions of high amplitude in the distal antrum. In the duodenum, two predominant activity patterns were noted: (i) periods of continuous irregular activity; and (ii) irregular clusters of contractions separated by quiescent intervals. No typical migrating motor complex activity was seen in the basal gastric or small bowel recordings. Bilateral vagal blockade did not consistently change the general pattern of gastric or small bowel activity, but did appear to reduce gastric contractile activity, as measured by motility indices. We conclude that extrinsic vagal innervation does not play a major role in the control of fasting feline gastric and duodenal motility.     

Radioemetic protection at 24 h after 60Co irradiation in both normal and postremectomized cats

The radioemetic dose-response relationships were established in 46 unanesthetized cats for each of two whole-body exposures, 24 h apart, to 60Co radiation at selected doses between 7.5 and 60 Gy. Individual episodes of vomiting were recorded for a period of 48 h as distinctive intrathoracic pressure deflections signaled through a catheter placed in the superior vena cava. Five cats with chronic lesions of the area postrema were included in the group exposed to 45 Gy. The lesioned animals were not detectably different in their radiation response behavior from the intact cats. Initial exposure in the entire cat series produced an increasing incidence of radioemesis from 25 to 80% over the specified dose range for the first observation period of 24 h. By contrast, the second exposure produced an inverse dose-related incidence of emesis varying from 63% to zero with an apparent crossover of radioemetic susceptibility for the two exposures at about 15 Gy. Complete protection during 12 h after the second exposure was obtained at 30, 45, and 60 Gy, and for all of 24 h at 45 and 60 Gy. In a separate group of 11 normal cats, the emetic drug xylazine invariably evoked vomiting when radioemetic protection was otherwise manifest after initial irradiation at 45 Gy. We conclude that the temporary recovery of well-being following acute lethal irradiation results selectively through increased radioemetic resistance, and it does not depend on the integrity of the area postrema.     

Regional intercostal activity during coughing and vomiting in decerebrate cats.

Regional variations in the discharge patterns of the internal and external intercostal muscles of the middle and caudad thorax were studied in decerebrate, spontaneously breathing cats during coughing and vomiting. Coughing, induced by electrical stimulation of the superior laryngeal nerves, consisted of increased and prolonged diaphragmatic activity followed by a burst of abdominal activity. Mid-thoracic external and internal intercostal muscles discharged synchronously with the diaphragm and abdominal muscles, respectively. Caudal external and internal intercostal muscles, however, discharged synchronously with the abdominal muscles. Vomiting, induced by stimulation of the lower thoracic vagi, consisted of a series of synchronous bursts of diaphragmatic and abdominal activity (retching) followed by a prolonged abdominal discharge after the cessation of diaphragmatic activity (expulsion). Caudal external and internal intercostals discharged in phase with diaphragmatic and abdominal activity but both mid-thoracic intercostal muscles discharged out of phase with these muscles. These results indicate major differences in the control and functional roles of intercostal muscles at different thoracic levels during these behaviours.     

Transmural pressure in the right atrium during positive pressure respiration in cats

The influence of continuous positive pressure breathing (cm H2O) on the breathing mechanics, central venous pressure, and transmural pressure in the right atrium, were studied in anaesthetised cats separately during inspiration and expiration. It's shown that hemodynamics effects are directly connected with the influence of increased intrathoracic pressure during whole breathing cycles in contrast with the phase changes in natural expiration and inspiration. The inversion of relation of intrathoracic and central venous pressure due to displacement of the mechanical respiratory characteristics became the factors defining the fall of the right atrium filling pressure.     

Effect of negative intrathoracic pressure on venous return

In acute experiments on cats and in observations made in human subjects, an increase of the negative intrathoracic pressure (NIP) leads to no significant changes of the venous return (VR) mean values. The peak values of the VR, however, increased and decreased more in inspiration and expiration following a deep breathing as compared with the normal breathing. The NIP seems to exert no direct effect upon the VR.     

Interspecific variation in the emetic response of anurans.

1. The emetic response of seven species (four genera) of frogs to apomorphine hydrochloride, copper sulfate, antimonyl potassium tartrate and mechanical stimulation at the esophageal orifice was surveyed. Xenopus laevis and Rhacophorus schlegelii were more sensitive to systemically administered apomorphine than were the other species tested. 2. The sensitivity of Rana rugosa to apomorphine varied with the season. 3. All of the species showed vigorous vomiting behavior after the oral administration of either copper sulfate or antimonyl potassium tartrate. 4. Mechanical stimulation also induced vomiting in all species. Although the species differed in sensitivity to the different emetic stimulants, the adaptive significance of this interspecific variation is not known. 5. From the stand point of the mechanics for ejecting gastric contents, there is little difference between frogs and mammals. 6. Frogs, particularly Xenopus laevis, may be a useful non-mammalian model for studying emesis.     

Effects of feeding on luminal pH and morphology of the gastroesophageal junction of snakes

At the gastroesophageal junction, most vertebrates possess a functional lower esophageal sphincter (LES) which may serve to regulate the passage of liquids and food into the stomach and prevent the reflux of gastric contents into the esophagus. Snakes seemingly lack an LES and consume meals large enough to extend anteriorly from the stomach into the esophagus thereby providing the opportunity for the reflux of gastric juices. To explore whether snakes experience or can prevent gastric reflux, we examined post-feeding changes of luminal pH of the distal esophagus and stomach, the fine scale luminal pH profile at the gastroesophageal junction, and the morphology of the gastroesophageal junction for the Burmese python (Python molurus), the African brown house snake (Lamprophis fuliginosus), and the diamondback water snake (Nerodia rhombifer). For each species fasted, there was no distension of the gastroesophageal junction and only modest changes in luminal pH from the distal esophagus into the stomach. Feeding resulted in marked distension and changes in tissue morphology of the gastroesophageal junction. Simultaneously, there was a significant decrease in luminal pH of the distal esophagus for pythons and house snakes, and for all three species a steep gradient in luminal pH decreasing across a 3-cm span from the distal edge of the esophagus into the proximal edge of the stomach. The moderate acidification of the distalmost portion of the esophagus for pythons and house snakes suggests that there is some anterior movement of gastric juices across the gastroesophageal junction. Given that this modest reflux of gastric fluid is localized to the most distal region of the esophagus, snakes are apparently able to prevent and protect against acid reflux in the absence of a functional LES.     

The dynamic of breathing biomechanics and intrathoracic hemodynamics parameters during microgravity modeling

In ground-based model of the hemodynamics effects of weightlessness, the intersystem relation of breathing and circulation was investigated during inspiration and expiration separately in anesthetized catz. It's shown that the dynamics of central venous pressure, esophageal pressure and filling pressure of the heart during inspiration in supine and head-down tilt position has obvious similarity to those which hypothetically can be present in microgravity. The results suggest that intrathoracic hemodynamics during inspiration in supine and head-down position may be an adequate ground model for investigation of weightlessness influences on intrathoracic circulation.     

Editorial: Aspects of violence.

A case of intramural esophageal hemorrhage in a hemodialysis patient is described. The hemorrhage followed an episode of vomiting and violent retching. Spontaneous resolution occurred with conservative management. The clinical course resembled that of previous case reports of intramural esophageal hemorrhage, whether or not associated with chronic renal failure and intermittent hemodialysis.     

Responses of the anterolateral abdominal muscles during cough and expiratory threshold loading in the cat.

The present study was conducted to determine the pattern of activation of the anterolateral abdominal muscles during the cough reflex. Electromyograms (EMGs) of the rectus abdominis, external oblique, internal oblique, transversus abdominis, and parasternal muscles were recorded along with gastric pressure in anesthetized cats. Cough was produced by mechanical stimulation of the lumen of the intrathoracic trachea or larynx. The pattern of EMG activation of these muscles during cough was compared with that during graded expiratory threshold loading (ETL; 1-30 cmH(2)O). ETL elicited differential recruitment of abdominal muscle EMG activity (transversus abdominis > internal oblique > rectus abdominis congruent with external oblique). In contrast, both laryngeal and tracheobronchial cough resulted in simultaneous activation of all four anterolateral abdominal muscles with peak EMG amplitudes 3- to 10-fold greater than those observed during the largest ETL. Gastric pressures during laryngeal and tracheobronchial cough were at least eightfold greater than those produced by the largest ETL. These results suggest that, unlike their behavior during expiratory loading, the anterolateral abdominal muscles act as a unit during cough.     

Gastroesophageal dynamics during immersion in water to the neck.

This investigation was undertaken to study the effect of hydrostatic pressure on gastroesophageal dynamics during immersion in thermoneutral water to the neck. In 5 healthy male subjects (normal end-expiratory), gastric pressure (PG), esophageal pressure (PE), location and pressure of distal esophageal sphincter (des), location of respiratory inversion point (RIP), and gastroesophageal pH gradient were measured standing in air (A), standing in water to the neck (B), and standing in air with abdominal compression (C). The pressure was measured with a Honeywell esophageal catheter (model 31) with built-in pressure transducer. A Beckman stomach pH electrode (no. 39042) was positioned adjacent to the pressure transducer. PG increased from 4.6 +/- 0.6 (SE) mmHg in A to nearly 20 mmHg in B and C, while PE increased from -6.0 +/- 0.8 mmHg in A to -0.8 +/- 1.0 and -3.4 +/- 0.9 mmHg in B and C, respectively. However, PDES was always 11-15 mmHg higher than PG. The superior limit of DES was displaced cephalad by indicating a stretching of DES and a shortening of the esophagus. Qualitatively similar findings were obtained in C. In all experiments, the esophageal pH remained above 6, and no alteration in the amplitude of primary peristaltic waves was seen. It is concluded that a head-out immersion with increased gastroesophageal pressure gradient predisposes to gastric reflux in the absence of a competent DES mechanism.     

Simulated breath-hold diving to 20 meters: cardiac performance in humans

Cardiac performance was assessed in six subjects breath-hold diving to 20 m in a hyperbaric chamber, while nonsubmersed or submersed in a thermoneutral environment. Cardiac index and systolic time intervals were obtained with impedance cardiography and intrathoracic pressure with an esophageal balloon. Breath holding at large lung volume (80% vital capacity) decreased cardiac index, probably by increasing intrathoracic pressure and thereby impeding venous return. During diving, cardiac index increased (compared with breath holding at the surface) by 35.1% in the nonsubmersed and by 29.5% in the submersed condition. This increase was attributed to a fall in intrathoracic pressure. Combination of the opposite effects of breath holding and diving to 20 m left cardiac performance unchanged during the dives (relative to the surface control). A larger intrathoracic blood redistribution probably explains a smaller reduction in intrathoracic pressure observed during submersed compared with nonsubmersed diving. Submersed breath-hold diving may entail a smaller risk of thoracic squeeze (lesser intrathoracic pressure drop) but a greater risk of overloading the central circulation (larger intrathoracic blood pooling) than simulated nonsubmersed diving.     

Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise.

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/"rib cage" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.     

Interspecific variation in the emetic response of anurans

1. The emetic response of seven species (four genera) of frogs to apomorphine hydrochloride, copper sulfate, antimonyl potassium tartrate and mechanical stimulation at the esophageal orifice was surveyed. Xenopus laevis and Rhacophorus schlegelii were more sensitive to systemically administered apomorphine than were the other species tested.2. The sensitivity of Rana rugosa to apomorphine varied with the season.3. All of the species showed vigorous vomiting behavior after the oral administration of either copper sulfate or antimonyl potassium tartrate.4. Mechanical stimulation also induced vomiting in all species. Although the species differed in sensitivity to the different emetic stimulants, the adaptive significance of this interspecific variation is not known.5. From the stand point of the mechanics for ejecting gastric contents, there is little difference between frogs and mammals.6. Frogs, particularly Xenopus laevis, may be a useful non-mammalian model for studying emesis.