Summary. Applying manometric methods a series of dog experiments wascarried out in order to test and analyse the therapeutic mechanism of fundoplication. The functioning of the fundus cuff was investigated in three different models:1. the anatomically intact, sufficient lower esophageal sphincter (LES); 2. the myotomized, insufficient LES; 3. after total extirpation of the terminal esophageal muscle (circular myomectomy).The following results have been obtained: Fundoplication prevents reliably gastro-esophageal reflux. Applying fundoplication however at a sufficient sphincter with normal pressure an unphysiologically high pressure barrier is established. According to manometry in all three models, the fundus cuff builds up its own pressure zone, which is subjected to similar hormone regulations as the LES itself. The cuff has to be made of a part of the anterior fundus wall, which is the only area with a reactivity comparable to that in the LES.According to the tests performed, the therapeutic mechanism of fundoplication seems to consist of an increase in pressure, which is due to the cuff. On the basis of the higher pressure level reflux is being prevented and there is a satisfactory reactivity of the high pressure zone. In addition, mechanical factors will have to be considered. The results obtained in animal experiments have been confirmed by manometric examinations in man after fundoplication.

The effect of clonidine on gastric acid secretion was investigated using rats and dogs. In the stomach lumen perfused rat basal gastric acid secretion was increased by clonidine in the anaesthetized rat but inhibited in the conscious animal. Clonidine also reduced the basal gastric acid secretion in rats with chronic gastric fistula, (ED50 12 microng/kg p.O.). In addition, gastric secretion stimulated by insulin hypoglycaemia was inhibited by clonidine in anaesthetized stomach lumen perfused rats and in conscious dogs with gastric fistula. In the rat gastric secretion stimulated by electrical vagus stimulation was inhibited as well. However, clonidine had no effect on the gastric acid secretion stimulated by carbachol in stomach lumen perfused rats and in dogs with denervated fundic pouch. These results suggest that the inhibition of gastric acid secretion by clonidine probably is due to an inhibition of acetylcholine release at the vagus nerve endings. Additional central gastric antisecretory effects can, however, not be excluded by this study.

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Abstract. 1. The continuous withdrawal method which has been used successfully in animal experiments for recording pressure profiles in the lower oesophageal sphincter, LES, was applied for the first time in human studies. A catheter with 4 side holes which served as a pressure transmitter, was continuously withdrawn from the stomach at a constant speed (6 mm/sec.) while constantly perfused (5 ml/min.). This procedure shows numerous advantages, particularly for quantitative analysis, when compared to both the stepwise pull‐through method and an open‐side catheter lying stationary in the sphincter. Thus the profiles obtained using the continuous withdrawal method are remarkable for their definition. Displacements, which can occur with a stationary catheter, are eliminated, and the pressure maximum can be definitely determined even if there is a shift in the area of maximum pressure. – 2. Pressure profiles of the LES taken with the withdrawal method in 20 conscious subjects usually showed a gradual, and then more rapid increase from aboral to oral, which after reaching a maximum value decreased steeply and changed into sub‐zero pressures. The maximum pressure taken from the pressure profiles of 20 subjects, being the mean value of all experiments, was 19 ± 7.3 mm Hg with a mean sphincter length of 3.4 ±0.6 cm (x̄±SD). The pressure profiles could be recorded at short intervals (0.5‐2 min.) without appreciable irritation of the sphincter. – 3. The continuous withdrawal method proved especially efficient, even after an increase of the sphincter tone induced by Pentagastrin (0.6 μg/kg I. V.). The mean results of the experiments in 6 test subjects showed that the maximum pressure in the LES increased from 13 ± 6.3 mm Hg to 44.2 ± 11 mm Hg 1 min. after the injection and the mean sphincter length increased from 3.9 ±1.2 cm to 5.3±1.4cm. These effects had subsided after 7–10 min. Pressure profiles obtained in this way, as well as supplementary measurements, indicated that Pentagastrin can cause a shift of the maximum pressure area in the oral direction.

The association between inflammatory cell influx, cell activation status and change of airway responsiveness to acetylcholine (ACh) after daily inhalation of ovalbumin (OA) in sensitized guinea-pigs was investigated. Starting 3 weeks after sensitization (OA at 50 mg/kg s.c.+i.p.) guinea-pigs were exposed daily to 2% OA (10 min; under cover of 0.5 mg/kg mepyramine i.p. 15 min before OA) for 2 weeks. Concentration-response curves (CRCs) for inhaled ACh were performed 24 h after the last OA-challenge and 24 h after another single OA-inhalation 1 week later. CRCs for inhaled ACh were neither affected 24 h after the last OA challenge (daily for two weeks) nor 24 h after another OA-inhalation one week later. In contrast, bronchoalveolar lavage (BAL) from repeatedly OA- sensitized/-challenged guinea-pigs immediately after the last CRC showed a significant increase of total cell count by about tenfold and increases in eosinophils by about 20-fold, neutrophils by 30-fold, macrophages by about fivefold and lymphocytes by about tenfold (P < 0.05, multiple Wilcoxon-test). In contrast, markers of cell activation (EPO, MPO) were significantly decreased (P < 0.05). Methylprednisolone almost completely prevented these changes in increased cell numbers and decreased cell activation (vs OA contr., P < 0.05). The lack of increased airway hyperresponsiveness despite a massive inflammatory cell influx suggests other factors controlling airway responsiveness than inflammation.