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Biomedical subjects

E L Gerring

Publications and source records attributed to E L Gerring.

At least 19 recordsLinked to original sources

Gastric emptying of four liquid meals in pony foals.

Water, saline and a saline/Intralipid mixture (lipid concentration 1.25 per cent) emptied very rapidly from the stomach in neonatal pony foals, and obeyed an apparently exponential pattern. Cisapride did not significantly modify the emptying of the saline/Intralipid mixture. Equine milk emptied more slowly. The data indicated that the lipid component of milk was not an important factor. Milk caused deviation from an exponential pattern in two of four foals: an initial lag phase appeared, which could represent a phase of intragastric processing. However, the rate was still rapid compared with results from human infants.

Animals↗

Gastric emptying of solid, non-digestible, radiopaque markers in ponies.

The gastric emptying of different forms of ingesta occurs by a variety of mechanisms and dysfunction may selectively affect different components of the gastric contents. A technique for assessing gastric emptying of solid, indigestible, radiopaque markers was developed. Emptying of these markers in four ponies was variable in both pattern and rate (half emptying time ranged from less than one hour to more than 24 hours). However, whereas in man physically similar markers appear to empty relatively rapidly when fasting but are delayed by a meal, no such delay was evident in these ponies. The horse does not interrupt cyclical motility when fed ad libitum. The data, therefore, suggest that the mechanism of emptying of non-digestible markers differs between man and the pony.

Animals↗

Twenty-four hour gastric pH monitoring and blood gastrin concentrations in fasted ponies.

Gastric pH varied widely among eight fasted ponies, of which seven exhibited discrete episodes of spontaneous alkalinisation (SA). SA occurred at all times of the study and no significant variation in the summary variables of pH (median pH, mean pH and percentage of readings exceeding pH 4.0) was noted among the periods 0 to eight, eight to 16 and 16 to 24 hours. The occurrence of SA has significant implications for the performance of acid secretory studies in the fasted pony. There was, however, no significant correlation between pH and plasma gastrin concentration measured using a commercially available radioimmunoassay kit validated for use in the horse. This implies a lack of dependency of the incidence of SA on plasma gastrin or, conversely, of plasma gastrin on the variable pH associated with SA.

Animals↗

Effects of single intravenously administered doses of omeprazole and ranitidine on intragastric pH and plasma gastrin concentration in nonfed ponies.

We investigated the effects of a range of IV administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of IV administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of IV administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administration. In the presence of acid-suppressant treatment, plasma gastrin concentration correlated significantly with gastric pH (Spearman's rank correlation coefficient, rho = 0.445, P < 0.01), whereas basal pH and plasma gastrin concentration were not correlated. The effect was not great, and a dose-dependency was not found. Intravenously administered omeprazole was subject to two-compartment pharmacokinetics, and there was evidence for saturable steps in the redistribution and elimination phases. Dosage of 0.25 mg/kg induced approximately half-maximal inhibition of basal gastric pH in these ponies and was associated with area under the concentration vs time curve of 0.7 mumol.h/L, which corresponds reasonably with results of other species. Omeprazole may represent a useful alternative acid-suppressant agent in horses, but further work is required to relate the dose-dependent effects found in this study to well-defined targets of acid suppression in clinical cases.

Analysis of Variance↗

Technique for prolonged, minimally invasive monitoring of intragastric pH in ponies.

Intragastric pH monitoring was investigated in ponies. In cadaver stomachs, close contact with the mucosa led to high pH readings if nonweighted electrodes were used. However, pH recorded by weighted electrodes was markedly less affected by mucosal contact (P < 0.001). The latter were used for subsequent trials. In vivo, high correlations were found between pH recorded by weighted electrodes with or without a wire guard to prevent mucosal contact (correlation, r = 0.866; P < 0.001). Readings from each correlated well with those from simultaneous gastric aspirates (r = 0.774 and r = 0.807, respectively; P < 0.001 for both correlations). Plain electrodes recorded more highly variable (temporally heterogeneous) pH than did guarded electrodes. In vitro, trials using equine gastric fluid indicated that this resulted from greater responsiveness of the plain electrode. In vivo, episodes of nearly neutral pH were a common feature, and high pH correlated with intensely yellow-green, neutral fluid in the stomach (rank correlation, rho = 0.626; P < 0.01). Concentration of bile acids did not correlate with pH or color score (rho = -0.158 and rho = 0.076, respectively). Causes of the episodes could include salivary influx, duodenogastric reflux, and variable gastric acid secretion. Pentagastrin infusion (0.6 microgram/kg of body weight/h) reduced intragastric pH (P = 0.018), but episodes of neutrality still occurred. Experiments in fed ponies indicated possible existence of a stable pH gradient, from neutral dorsally to heterogeneous and more acidic ventrally. Care was required in the rational choice of summary variables for expression of monitored pH data. Of the frequency distributions of 3 summary variables assessed in this study (mean, median, and percentage of data > pH 4), only that of the mean approached normality. Thus, use of the mean may allow analysis by parametric statistical methods. Intragastric pH monitoring was found to be a useful technique. Episodes of increased pH were often identified. These may represent episodic duodenogastric reflux.

Animals↗

Gastric pH monitoring in healthy, suckling pony foals.

Gastric pH was monitored in neonatal foals from birth to 3 months of age. Background pH decreased, especially during the first week of life. Milk had complex effects that depended on pH prior to sucking, confounded by the age of the foal: nearly neutral background pH tended to be acidified after milk intake; moderately acid background pH tended to be neutralized; low background pH was only slightly increased by milk. Absolute magnitude of the effects of milk decreased with age. Existence of a proulcerative intragastric environment in preweaning foals is postulated, but this must be considered in the context of what probably is a multifactorial pathogenesis.

Animals↗

The action of low dose endotoxin on equine bowel motility.

Post operative ileus (POI) is a common and serious complication of colic surgery in the horse. There is a high correlation between the incidence of POI and the presence of ischaemic bowel, suggesting a role for endotoxin. 0.1 micrograms/kg endotoxin was administered intravenously to six ponies with chronically implanted gastrointestinal electromechanical recording devices. It produced profound disruption of normal fasting bowel motility patterns, with an inhibition of gastric contraction amplitude and rate, left dorsal colon contraction product and small colon spike rate. In the small intestine an increase in abnormally arranged regular activity and a decrease in irregular activity was observed. There was no significant prolongation in stomach to anus transit time as assessed by the passage of plastic spheres. The bowel motility patterns induced by endotoxin could be mimicked by the intravenous infusion of PGE2 and less potently by PGI2 (prostacyclin), but not by PGF2 alpha. This study provides evidence that systematic endotoxin present in clinical cases of colic may play a role in the pathogenesis of equine ileus. The acute effects of endotoxin on bowel motility appear to be mediated indirectly by prostaglandins, and the inhibitory effects may be mediated mainly by PGE2.

Animals↗

Antagonism of endotoxin-induced disruption of equine gastrointestinal motility with the platelet-activating factor antagonist WEB 2086.

The effect of pre-treatment with a selective platelet-activating factor (PAF) antagonist, WEB 2086, on the actions of low-dose endotoxin was evaluated in ponies prepared with gastrointestinal strain gauges. Endotoxin (0.1 microgram/kg i.v.) produced a marked reduction in gastric contraction amplitude and rate, and an increased frequency and reduced duration of jejunal phase III activity fronts (AFs). WEB 2086 (6.6 mg/kg) administered i.v. 10 min before the endotoxin, produced significant antagonism (P less than 0.001) of the effect of endotoxin on gastric contraction amplitude and rate. The combination of WEB 2086 and endotoxin produced gastric contractions of significantly (P less than 0.01) higher frequency than in the control studies. WEB 2086 also reduced endotoxin-induced abnormal phase III AFs in the jejunum and increases in heart rate and packed cell volume. These results provide evidence that endogenous PAF plays a role in mediating the acute effects of endotoxin on equine gastrointestinal motility.

Animals↗

Effects of pharmacological agents on gastrointestinal motility.

The control mechanisms of gastrointestinal motility are complex. Extrinsic neurohormonal effects modulate an intrinsic system, often called the "gut brain," composed of nervous and neuropeptide components. To exert pharmacologic influence on GI motility, use is made of agents that mimic the external control system. Agents that stimulate opioid receptors, block adrenoceptors, block or facilitate acetylcholine action, or antagonize the action of prostaglandins are used to effect changes in GI motility. The major indications for pharmacologic intervention are to increase motility in constipation, to reduce it in most cases of diarrhea, and to restore propulsive coordination in postoperative ileus. In cases of clinical colic the primary requirement is control of pain. Agents used for this purpose may adversely affect motility, and choice requires knowledge of their actions in this respect. In addition, drugs used for other purposes, anthelmintics for instance, may also influence gut motility. A synopsis of the actions of the agents commonly employed in GI motility control and some associated drugs are displayed in Table 3. Recent advances in the understanding of drug action on the gut should help in the selection of drugs for clinical use.

Animals↗

Antagonism of endotoxin-induced disruption of equine bowel motility by flunixin and phenylbutazone.

Post operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre-treatment with intravenous (i.v.) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 microgram/kg bwt i.v. endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P < 0.01) for the stomach and left dorsal colon. Both drugs reduced the acute systemic side-effects of the endotoxin and flunixin was slightly more effective than phenylbutazone in antagonising the cardiovascular effects. These results suggest that the acute effects of endotoxin on bowel motility are mediated at least in part by a cyclooxygenase dependent pathway. Flunixin and phenylbutazone showed a relative selectivity for the cardiovascular and gastrointestinal effects of endotoxin, respectively. Phenylbutazone may be of use clinically in acute colic cases, antagonising the disruptive effects of endotoxin on bowel motility, without entirely blocking the cardiovascular effects which can indicate that the patient has a condition requiring surgery.

Animals↗

Observations on the colic motor complex in a pony with a small intestinal obstruction.

Characteristic motility patterns were seen throughout the gastrointestinal tract in a pony prepared chronically with electromechanical recording devices after developing a simple obstruction of the small intestine. Gross distension of the stomach with fluid produced loss of gastric contractile activity and a chaotic electrogram. These changes were reversed instantaneously when the stomach was decompressed. In the jejunum, proximal to the obstruction, the unique 'colic motor complex' was observed with contractions of longer duration arranged in characteristic pulses of activity. The left dorsal colon showed continuous hyperactivity and the small colon remained active. Abnormal motility patterns occurring secondary to a small intestinal obstruction could play a role in the aetiology of small and large intestinal disorders.

Animals↗

Cisapride in the prophylaxis of equine post operative ileus.

Cisapride and domperidone were both effective in restoring electrical and mechanical activity, coordination between gastric and small intestinal activity cycles and the stomach to anus transit time in three ponies in which post operative ileus was induced experimentally. Cisapride (0.1 mg/kg bodyweight intramuscularly) for three to eight doses prevented idiopathic post operative ileus in 22 clinical cases requiring colic surgery. The only side effects after cisapride were increased bowel sounds and slight, transient sounds of discomfort. No adverse side effects were seen in 16 cases following anastomosis or enterotomy. Cisapride appears safe and effective in the prophylaxis of equine post operative ileus.

Animals↗

Detection of endotoxin in cases of equine colic.

The Limulus amoebocyte lysate assay was used to test for the presence of endotoxin in 37 clinical cases of equine colic. Positive plasma titres were detected in 10 cases and the presence of endotoxin was significantly correlated with a high heart rate, a high packed cell volume and a poor prognosis. High levels of endotoxin were detected in gut contents taken from several sites in the gastrointestinal tract of normal horses.

Animals↗

Actions of the novel gastrointestinal prokinetic agent cisapride on equine bowel motility.

The effect of cisapride was evaluated on the normal fasting bowel motility of four ponies with chronically implanted electromechanical transducers. Cisapride was infused over 60-min periods at 0.05 mg/kg (n = 4), 0.1 mg/kg (n = 5) and 0.25 mg/kg (n = 5). It produced marked and prolonged increases in electrical and mechanical activity at all sites examined. In the stomach there was increased total contraction activity with increased contraction amplitude and a slight reduction in rate. In the small intestine there was an increase in irregular (phase II) activity with an increase in number and amplitude of contractions and a decrease in the number of regular (phase III) activity fronts. There was a decrease in the number of phase III fronts that spread distally from the jejunum to the ileum. The phase II activity was coordinated temporally with prolonged activity in the stomach. Cisapride increased electrical and contractile activity in the left dorsal colon with increased contraction amplitude and an increase in electrical activity in the small colon. In the stomach and small intestine cisapride produced dose-dependent increases in activity but in the left dorsal and small colon the intermediate dose (0.1 mg/kg) produced the largest and most consistent responses. Side-effects observed were increased bowel sounds and frequency of defaecation, a slight increase in heart rate and transient signs of discomfort at the highest (0.25 mg/kg) dose rate.

Animals↗