Increased sensitivity to stimulation of acid secretion by pentagastrin in duodenal ulcer.

The effect of graded doses of pentagastrin (2.7-6,000 ng/kg times h) on gastric acid secretion was measured in 20 duodenal ulcer (DU) and 20 non-DU subjects. Confirming many previous studies, the mean observed highest response and the mean calculated maximal response were significantly greater in DU than in non-DU subjects. The mean dose (plus or minus SE) in ng/kg times h for half maximal response, calculated from responses corrected for basal secretion and normalized for maximal secretion, was 92.1 plus or minus 1.7 in DU and 246.8 plus or minus 24.6 in non-DU subjects, a significant difference. By parallel line bioassay non-DU subjects required 2.8 times more pentagastrin (95% confidence limits 2.1-3.7) than DU highest response. Thus, this study shows that, compared with non-DU subjects, DU patients not only secrete more acid in response to stimulation by pentagastrin but also are more sensitive to stimulation by pentagastrin, that is, need smaller doses to achieve the same fraction of maximal response.     

Oxyntomodulin: a potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man

Synthetic oxyntomodulin, a predicted product of the glucagon gene, which is produced in the human lower intestinal mucosa, was infused in doses of 100 and 400 ng kg-1 h-1 into six volunteers to study its pharmacokinetics and effects on pentagastrin-stimulated gastric acid secretion (100 ng kg-1 h-1). The concentration of oxyntomodulin in plasma measured with a cross-reacting glucagon assay increased from 37 +/- 5 to 106 +/- 17 and 301 +/- 40 pmol l-1, respectively. The metabolic clearance rate was 5.2 +/- 0.7 ml kg-1 min-1 and the half-life in plasma was 12 +/- 1 min. Oxyntomodulin reduced the pentagastrin-stimulated acid secretion by 20 +/- 9% during the low-rate infusion (P less than 0.05) and by 76 +/- 10% during the high-rate infusion (P less than 0.05). In accordance with the homology with glucagon, there was a small, significant rise in plasma concentrations of insulin and insulin C-peptide during oxyntomodulin infusion. Oxyntomodulin may therefore be included among the potential incretins and enterogastrones in man.     

Enterogastrone-like effect of peptide YY is vagally mediated in the dog.

Intraluminal fat inhibits gastric secretion through as yet undetermined mechanisms which involve release of one or more hormonal enterogastrones. As intraluminal fat releases Peptide YY (PYY) in amounts sufficient to inhibit meal-stimulated acid secretion, this ileo-colonic peptide exhibits the characteristics required of an enterogastrone. The present study seeks to determine the mechanism by which PYY inhibits acid secretion by examining the effects of PYY on gastric acid stimulated by pentagastrin, histamine, and bethanechol. In addition, effects of PYY on the acid response to sham feeding and distention of a denervated gastric pouch were examined. A dose of PYY (400 pmol X kg-1 X h-1) was employed that reproduced blood levels observed after intestinal perfusion with oleic acid and inhibited the acid secretory response to an intragastric meal by 35 +/- 6%. This same dose of PYY maximally inhibited histamine- and pentagastrin-stimulated acid secretion by 28 +/- 7% (P less than 0.05), and 17 +/- 4% (P less than 0.05), respectively. Although PYY had no effect on bethanechol-stimulated secretion it markedly inhibited the secretory response to sham feeding, maximally reducing secretion by 90 +/- 4% (P less than 0.01). We speculate that PYY acts by inhibiting acetylcholine release from vagal nerve fibers rather than by inhibiting acetylcholine's action on the parietal cell. The demonstration that PYY virtually abolishes cephalic phase acid secretion while having little if any effect on the response to exogenous secretogogues gives PYY unique characteristics among the known hormonal inhibitors of gastric secretion.     

Effects of spiroglumide, a gastrin receptor antagonist, on acid secretion in humans

BACKGROUND: A gastrin receptor antagonist, CR2194 (spiroglumide), was used to explore the physiological role of gastrin in regulating gastric acid secretion in humans. MATERIALS AND METHODS: The effect of CR2194 on inhibition of gastrin-stimulated acid output was evaluated in a four-period crossover study. Each subject received intravenous doses of 1, 2.5 or 7.5 mg kg-1 h-1 CR2194 or saline (control) followed by graded increasing doses of gastrin (6.4-800 pmol kg-1 h-1). Secondly, the effect of CR2194 on meal-stimulated intragastric acidity was evaluated by infusing either saline (control) or CR2194 (7.5 mg kg-1 h-1) before and after food ingestion. RESULTS: Acid secretion was dose-dependently inhibited by CR2194. With CR2194, acidity was significantly reduced in the pre-meal and post-prandial period (P < 0.01 and 0.002 respectively), and the integrated gastrin response was augmented to 8.0 +/- 1.4 ng mL-1 240 min compared with 1.5 +/- 0.8 ng mL-1 240 min in the control experiment (P < 0.01). Finally, acid secretion in response to sham feeding was significantly reduced: 15.9 +/- 0.9 mmol 90 min-1 in the control experiment compared with 2.8 +/- 0.9 mmol 90 min-1 during CR2194 infusion (P < 0.05). CONCLUSION: Gastrin receptor blockade with CR2194 alters gastric acid secretion in response to food ingestion or to sham feeding. The results support a physiological role for gastrin in regulating acid secretion in humans.     

Gastric bicarbonate secretion in humans. Effect of pentagastrin, bethanechol, and 11,16,16-trimethyl prostaglandin E2.

Although the stomach is mainly known for its ability to secrete hydrochloric acid, there is increasing evidence that the gastric mucosa also secretes bicarbonate. A simple method for simultaneous measurement of gastric HCO-3 secretion and H+ secretion was developed from a two-component model of gastric secretion. The method, which is based upon gastric juice volume, H+ concentration, and osmolality, was validated both in vitro and in vivo. In 14 healthy human beings, basal gastric HCO-3 secretion averaged 2.6 mmol/h (range, 0.7-8.7 mmol/h). Basal HCO-3 secretion was approximately 50% of basal H+ secretion and there was a significant correlation between basal HCO-3 and H+ secretion in individual subjects (r = 0.79). HCO-3 was secreted in basal nonparietal secretion at a concentration of approximately 90 mmol/liter. Intravenous pentagastrin infusion markedly stimulated H+ secretion but did not increase HCO-3 secretion. During pentagastrin infusion, the cholinergic agonist, bethanechol, significantly augmented H+ secretion (from 20.2 to 24.7 mmol/h) and increased HCO-3 secretion (from 2.2 to 4.2 mmol/h). A prostaglandin E2 analogue significantly reduced H+ secretion and increased HCO-3 secretion during pentagastrin infusion. The reduction in net gastric juice H+ output following prostaglandin E2 was due more to H+ secretory inhibition than to HCO-3 secretory stimulation. We conclude that the healthy human stomach actively secretes HCO-3 and that gastric HCO-3 secretion can be influenced by cholinergic stimulation and by prostaglandin E2.     

Histamine release in vivo by pentagastrin from the canine stomach

The effect of intragastric arterial infusion of pentagastrin on gastric histamine release was evaluated in mongrel dogs in vivo. Histamine secretory rates were evaluated by measuring the arterial and gastric venous plasma histamine concentrations at 0, 5, 10, 15 and 20 min into pentagastrin infusions, and gastric blood flow was continuously monitored. Histamine secretory rates were calculated by subtracting the arterial from the venous histamine concentrations and multiplying the difference by gastric plasma flow. Two separate 20-min infusions of pentagastrin, separated by 60 min, resulted in a peak of histamine release in 5 to 10 min that returned to base line within 20 min. During the first infusion, histamine release peaked at 179 ng/min, whereas, during the second infusion, histamine peaked at 125 ng/ml. The increase in gastric blood flow to pentagastrin correlated with the increases in histamine release. Somatostatin infused into the gastric artery to attain a concentration of 10 nM, a concentration that results in the inhibition of gastric acid secretion, abolished the gastric histamine release to pentagastrin. In addition, somatostatin also attenuated the gastric vasodilation to pentagastrin. Our data indicate that, in the in vivo dog model, pentagastrin can cause a pulsed release of gastric histamine, and somatostatin inhibits this release of histamine.     

Corticotropin-releasing factor. Mechanisms to inhibit gastric acid secretion in conscious dogs.

Immunoreactivity similar to that of corticotropin-releasing factor (CRF) is found in regions of the central nervous system that modulate autonomic responses, including gastrointestinal functions. We examined the central nervous system effects of ovine CRF on gastric acid secretion in conscious dogs. Male beagle dogs (11-13 kg) were fitted with chronic intracerebroventricular cannulae and gastric fistulae. Gastric acid secretion in response to intravenously administered gastric secretory stimuli was measured by in vitro titration of gastric juice to pH 7.0 and in response to an intragastric meal by in vivo intragastric titration at pH 5.0. Plasma gastrin was determined by radioimmunoassay. CRF microinjected into the third cerebral ventricle decreased pentagastrin-stimulated gastric acid secretion for 3 h (P less than 0.01) dose-dependently (0.2-6.0 nmol X kg-1). CRF did not inhibit histamine-stimulated gastric secretion but significantly (P less than 0.01) decreased the secretory response after 2-deoxy-D-glucose for 3 h. The gastric inhibitory action of intracerebroventricularly administered CRF on pentagastrin-stimulated gastric acid secretion was completely abolished by ganglionic blockade with chlorisondamine. The opioid antagonist, naloxone, and the vasopressin antagonist, [1-deaminopenicillamine,2-(O-methyl) tyrosine,8-arginine]-vasopressin, significantly suppressed the inhibitory effect of CRF on gastric acid secretion stimulated by pentagastrin. In contrast, truncal vagotomy did not prevent the inhibition of gastric acid secretion induced by CRF. CRF (0.2-2.0 nmol X kg-1) administered intracerebroventricularly decreased gastric acid secretion stimulated by 200-ml liquid meals containing 8% peptone. CRF did not affect plasma gastrin concentrations. These results indicate that CRF microinjected into the third cerebral ventricle inhibits gastric acid secretion in conscious dogs. CRF-induced inhibition of gastric acid secretion appears to be mediated by the sympathetic nervous system and, in part, by opiate and vasopressin-dependent mechanisms.     

Regulation of gastric acid secretion by neurotensin in man. Evidence against a hormonal role.

The present study was designed to evaluate neurotensin as a hormonal regulator of gastric acid secretion in man. After a fat-rich meal, the strongest known stimulus of neurotensin release, plasma neurotensin-like immunoreactivity (NTLI) was elevated from 7.6 +/- 1.9 to 15.5 +/- 2.5 pM. Plasma NTLI was measured with antiserum L170, which requires the biologically active carboxyl-terminal hexapeptide of the neurotensin molecule for recognition and does not crossreact significantly with any known natural catabolite in human plasma. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 resulted in a plasma level of 14.7 +/- 2.1 pM, similar to the maximal physiological level observed after the fat-rich meal. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 during 2 h, however, failed to significantly inhibit peptone meal-stimulated gastric acid secretion measured by intragastric titration. The 2-h acid output to peptone was 40.8 +/- 6.2 and 41.3 +/- 6.9 mmol during the vehicle and the neurotensin infusion, respectively. Intravenous infusion of neurotensin at 100 or 400 pmol X kg-1 h-1 did not affect acid output, whereas at 1,600 pmol X kg-1 h-1, which resulted in a plasma neurotensin concentration of 725 +/- 80 pM, significantly reduced peptone meal-stimulated gastric acid secretion. The neurotensin-induced inhibition of acid output was independent of the hormone gastrin. The present results provide evidence against a hormonal role for neurotensin in the regulation of meal-stimulated gastric acid secretion in man.     

Cyclic adenosine monophosphate and human gastric acid secretion.

This report concerns gastric juice, plasma, and urinary levels of adenosine 3',5'-monophosphate (cAMP) in 27 subjects undergoing routine gastric analysis under maximum stimulation with betazole or pentagastrin. Cyclic AMP was measured by sensitive and specific radioimmunoassay. No increase in concentration of cAMP was noted in gastric juice, plasma, or urine following either betazole or pentagastrin stimulation. Betazole-stimulated human gastric acid secretion was associated with an increased cAMP output into the gastric juice (P less than 0.05). There was no change in cAMP output following pentagastrin stimulation. The peak acid output produced by pentagastrin and betazole was similar. The lack of increase in cAMP concentration lends support to the concept that cyclic AMP is not a primary mediator in the stimulation of gastric acid secretion by betazole or pentagastrin in the human. The physiologic significance of the increase in cAMP output following betazole stimulation remains unresolved.     

Functional effects of pentagastrin and diagnostic possibilities of the pentagastrin test

The effect on gastric secretion of a single pentagastrin dose (6 micrograms/kg) against submaximal doses of histamine, euphylline and limontar was studied in 100 healthy subjects aged 20-30. It is shown that pentagastrin test corresponds to maximal histamine test allowing rough measurement of lining cells mass. Normal secretory values and mass of the lining cells have been established as well as normal secretory response of the stomach to submaximal histamine (0.008 mg/kg) and euphylline (7 mg/kg) tests. Diagnostic significance of the pentagastrin test in peptic ulcer and chronic gastritis with secretory insufficiency has been supported. There were some cases of secretory response to euphylline and limontar in pentagastrin-refractory forms of gastric secretion due to mobilization of functional cellular component of the gastric glands. Pentagastrin inhibited initially enhanced gastric evacuation though motor function of the stomach showed no response.     

Desensitization within and between secretagogues of canine gastric acid and pepsin secretion

Two types of desensitization, autodesensitization and cross-desensitization, of gastric secretory responses to cholinergic (bethanechol and vagal excitation) and noncholinergic stimuli (histamine and pentagastrin) were studied in groups of three to six conscious dogs with gastric fistula. Autodesensitization was manifested as fade of both acid and pepsin secretory responses by 10 to 20%/hr from peak output with all stimuli, histamine, pentagastrin and bethanechol. At the end of 4 hr of pentagastrin, 1.5 micrograms/kg X hr, doubling the dose of pentagastrin for 75 min reversed partly the trend of the acid fade, whereas adding an equipotent dose of histamine was much more effective, i.e., pentagastrin does not desensitize the stomach to histamine. When the three stimuli were given in sequence in random order for 2.5, 1.5 and 1.5 hr, respectively, to study cross-desensitization, histamine and pentagastrin reduced markedly the response of the parietal cells to either direct (bethanechol) or indirect (vagal) subsequent cholinergic stimulation. However, the parietal cells unresponsive to bethanechol remained fully responsive to histamine or pentagastrin, i.e., cholinergic stimulation did not desensitize the stomach to noncholinergic stimuli. From present and published data, neither auto- nor cross-desensitization is due to general, e.g. electrolyte and water depletion, or local, e.g. pH or osmolality, homeostatic consequences of secretion or to the drugs used, e.g. fall in blood pressure with histamine, but to cellular events. Inasmuch as the cell unresponsive to one stimulus may respond to another, a working hypothesis involving receptors is presented.     

Sialic acid secretion of patients with gastric and duodenal ulcers in the dose-response pentastrin test.

The secretion of HCl and sialic acid into the gastric juice was investigated in 13 patients with gastric, 52 with duodenal ulcers and 27 control patients, during the dose-response pentagastrin test. The basal output of sialic acid was clearly highest in patients with gastric ulcers, and the differences between these and other groups of patients were significant. During pentagastrin stimulation a significant initial decrease was found in patients with gastric ulcers with small doses, and the minimum was reached with a dose of 0.1 micrograms/kg/h. After increasing the dose, an increase in sialic acid output occurred in all groups, reaching its maximum with a pentagastrin infusion rate of 1.0 micrograms/kg/h. The basal concentration of sialic acid was also highest in patients with gastric ulcers. In all groups the concentration decreased during the stimulation, which obviously depended on the sialic output not increasing in the same relationship as the volume of gastric secretion.     

Increased sensitivity of gastric acid secretion to gastrin in cirrhotic patients with portacaval shunt.

We studied acid secretory responses to exogenous pentagastrin and to exogenous and endogenous gastrin in 12 stable cirrhotic subjects with portacaval shunt, 12 unshunted cirrhotics, and 12 normal subjects. Basal and stimulated serum gastrin concentrations as well as basal and maximum acid outputs were similar in the three groups. At low doses of either exogenous pentagastrin or gastrin-17 (G17), cirrhotics with portacaval shunt secreted significantly greater amounts of gastric acid than unshunted subjects. After low doses of intragastric peptone, cirrhotics with portacaval shunt secreted significantly more acid than unshunted cirrhotics and normal subjects. At each measured serum gastrin concentration after either exogenous G17 or intragastric peptone meals, cirrhotics with portacaval shunt secreted more acid than the unshunted control groups and their dose-response curve was significantly shifted to the left. Thus, in cirrhotic patients with portacaval shunt, gastric acid secretion is abnormally sensitive to both exogenously administered or endogenously released gastrin.     

Alpha-1 adrenoceptors mediate splanchnic nerve inhibition of pentagastrin-induced gastric acid secretion and mucosal blood flow in rats

Effects of stimulation of the sympathetic nervous system on pentagastrin-induced increases in gastric acid secretion and mucosal blood flow (MBF) were studied in anesthetized, gastric fistula rats. Gastric acid secretion and MBF were increased by i.v. infusion of a submaximal dose of pentagastrin (1.0 microgram/kg/min). Stimulation of the splanchnic nerve was carried out under the steady, increased state of pentagastrin-stimulated acid secretion and MBF. Stimulation of the splanchnic nerve significantly reduced gastric acid secretion, while MBF was little affected. Thus, the delta MBF/delta H+ ratio was significantly increased during this stimulation. Phentolamine, but not propranolol, abolished the inhibitory effects of splanchnic nerve stimulation on the pentagastrin-stimulated gastric acid secretion. In addition, prazosin, but not yohimbine, abolished the inhibitory effects of splanchnic nerve stimulation on the pentagastrin-induced gastric acid secretion. These results suggest that splanchnic nerves directly inhibit pentagastrin-induced gastric acid secretion through alpha-1 adrenoceptors, independently of changes in the MBF, in rats.     

Effect of chronic sham feeding on maximal gastric acid secretion in the dog.

The reason for increased maximal acid secretory capacity in some patients with duodenal ulcer is uncertain. We postulated that chronically increased cephalic-vagal stimulation may be a cause of increased maximal acid output. To study this, we prepared six male, mongrel dogs with a vagally innervated gastric fistula, a vagally denervated fundic (Heidenhain) pouch, and a cervical esophagostomy. Physiological cephalic-vagal stimulation was accomplished by sham feeding, which increased acid output from the vagally innervated stomach but not from the vagally denervated pouch. During an initial 6-wk control period, dogs were fed by mouth once daily at 3 p.m. Then, a 6-wk period of sham feeding was carried out, during which animals were sham fed with blenderized dog chow from 8 a.m. to 3 p.m. every day (a 7-h period of continuous cephalic-vagal stimulation), after which animals were fed by mouth. After 6 wk of daily sham feeding, maximal acid output in response to intravenous pentagastrin (16 micrograms/kg per h) increased by 27 +/- 4% in the vagally innervated stomach (P less than 0.01). Maximal acid output then returned to control levels after a final 6-wk recovery period with no sham feeding. No changes in maximal acid output occurred in the vagally denervated pouch during the 18-wk study. No changes in basal acid secretion or responsiveness of parietal cells to submaximal doses of pentagastrin occurred in the fistula or pouch during chronic sham feeding. We conclude that chronic physiological cephalic-vagal stimulation can increase maximal acid secretory capacity. Our studies also suggest that the effect of chronically increased vagal stimulation on maximal acid secretory capacity is reversible.     

Histamine H-2 receptor stimulation and inhibition of pepsin secretion in the dog

Although low doses of histamine (less than 150 nM/kg.hr) stimulate pepsin secretion, higher doses inhibit pepsin secretion in a dose-dependent manner. To better histamine stimulation of pepsin, histamine was used at doses at the lower end of the dose-response scale in five dogs with gastric fistula. Five doses of histamine below the ED50 for acid, viz, 9, 22.5, 67.5, 90 and 112 nM/kg.hr in 45-min steps, provided values for pepsin secretion from which Ed50 = 11.4 nmol/kg.hr (i.e., about 1/12 the ED50 for acid) and calculated maximum 22,600 peptic U/30 min were calculated. To document the inhibition, pepsin secretion was first stimulated by an infusion of bethanechol (0.4 mumol/kg.hr). A super-added injection of the histamine H-2 agonist 4-methylhistamine (0.4 or 0.8 mumol/kg) produced strong additional acid stimulation and immediate 40% suppression of pepsin secretion. The ratio pepsin/acid was reduced to one-third of control for the 90 min after 4-methylhistamine. The most specific H-2 agonist impromidine had the same effects, whereas pentagastrin (1.95 nmol/kg) inhibited both acid and pepsin secretion stimulated by bethanechol. The specificity of H-2 effect of impromidine was confirmed by simultaneous tachycardia and hypotension; pentagastrin did not produce cardiovascular effects. These studies confirm the unique effect of histamine on the peptic cell of the dog in which both stimulation and inhibition are H-2 receptor-mediated effects.     

Intravenous nizatidine kinetics and acid suppression

The effectiveness of intravenous nizatidine in suppressing gastric acid secretion was evaluated by different methods of inducing secretion in two single-blind studies. In study 1, seven subjects were given single, 20-min intravenous infusions of nizatidine (6.25, 25, 75, 150, or 250 mg) before modified sham feeding (MSF). Gastric acid suppression after nizatidine was contrasted with that after placebo and MSF. All doses of nizatidine reduced secretion; the 150- and 250-mg doses of nizatidine suppressed secretion for at least 2.5 hr. In study 2, eight subjects received one 5-min intravenous infusion of placebo, cimetidine (300 mg), or nizatidine (25, 50, 100, or 250 mg) weekly for 6 wk. Secretion was induced by infusing pentagastrin (2 micrograms/kg/hr) 45 min before the study drug was dosed and for 3.5 hr thereafter. Again, all doses of nizatidine reduced gastric acid, chiefly by decreasing volume. Nizatidine induced a clear dose-response effect; nizatidine (100 mg) and cimetidine (300 mg) had approximately equal suppressive effects. Nizatidine (100 mg) and cimetidine (300 mg) reduced acid output by 62% and 63% and reduced volume of secretion by 48% and 51% over the 3.5-hr period. Gastric acid suppression and plasma nizatidine concentrations were directly related. Nizatidine kinetics were linear and proportional to dose. The t1/2 was 1.3 hr (range 0.7 to 2.1 hr), the volume of distribution was 1.2 +/- 0.5 l/kg, and clearance was 0.6 +/- 0.2 l/kg/hr. Laboratory abnormalities and side effects were minor in both studies.     

Serotonin depletion potentiates gastric secretory and motor responses to vagal but not peripheral gastric stimulants

Vagal stimulation is known to release gastrointestinal serotonin. The effect of depletion of serotonin stores on vagally stimulated gastric acid secretion and motility was studied in rats. Pretreatment of rats with parachlorophenylalanine (p-CPA) did not alter basal gastric acid and serotonin secretion but produced a 57% reduction in the intraluminal gastric release of serotonin and a 43 to 100% potentiation of the gastric acid secretory response elicited by intracisternal injection of the stable thyrotropin-releasing hormone analog, RX 77368, in conscious pylorus-ligated rats or urethane-anesthetized rats with an acute gastric fistula. Dose-response studies revealed that the gastric acid secretion induced by submaximal but not high doses of RX 77368 was elevated significantly by p-CPA pretreatment. p-CPA also enhanced the gastric acid output produced by submaximal, but not high doses of the vagal stimulant baclofen, [beta-(p-chlorophenyl)-gamma-aminobutyric acid]. In contrast, p-CPA pretreatment had no effect on gastric acid secretion stimulated by bethanechol, histamine or pentagastrin. Selective depletion of central serotonin stores by pretreatment with the neurotoxin 5,7-dihydroxytryptamine given alone, or combined with parachloroamphetamine did not alter RX 77368-stimulated gastric acid secretion. In addition, gastric contractility stimulated by intracisternal injection of RX 77368 was significantly enhanced by p-CPA but not by 5,7-dihydroxytryptamine pretreatment, whereas the contractile response to carbachol was not altered by p-CPA pretreatment. These results suggest that depletion of peripheral but not central serotonergic stores potentiate gastric acid secretion and contractility induced by vagally, but not peripherally acting gastric stimulants. Thus, peripheral serotonin may exert an inhibitory tone on vagally stimulated gastric acid secretion and motility in the rat.     

The use of midazolam versus propofol for short-term sedation following coronary artery bypass grafting

Midazolam and propofol were compared in an open randomized study for postoperative sedation during 12 h of mechanical ventilation in 40 patients following coronary artery bypass grafting. After an intravenous loading dose of midazolam (50 micrograms.kg-1) or propofol (500 micrograms.kg-1), a titrated continuous infusion was administered of midazolam (mean dose 38.1 micrograms.kg-1.h-1 (SEM 2.6)) or propofol (mean dose 909 micrograms.kg-1.h-1 (SEM 100)) together with a narcotic analgesic infusion. During mechanical ventilation midazolam and propofol produced a similar quality of sedation, but recovery (midazolam 66 min (SEM 16); propofol 24 min (SEM 7)) and weaning from the ventilator (midazolam 243 min (SEM 44); propofol 154 min (SEM 33)) where faster with propofol. In the 2 groups administration of an intravenous loading dose caused a significant decrease in mean arterial pressure but hemodynamic tolerance during maintenance infusion was good.     

Inhibitory effect of bromazepam on insulin-stimulated gastric acid secretion in man.

The action of bromazepam on insulin-stimulated gastric acid secretion was examined in 5 healthy volunteers in a randomized study. To measure acid output, the intragastric titration technique and a pH-sensitive telemetering capsule were used. Three series of experiments were performed: (1) insulin (0.2 U/kg body weight), stimulation alone; (2) simultaneous injection of insulin and bromazepam (0.1 mg/kg body weight), subjects kept awake; (3) synchronous injection of insulin and bromazepam but with subjects allowed to fall asleep after drug administration. In all three series after insulin administration a significant initial inhibition of gastric secretion occurred. There were no significant differences between the three series regarding the intensity of hypoglycemia. Blood glucose levels lower than 25 mg/100 ml were reached in all experiments. Bromazepam in subjects kept awake caused drowsiness and a lower gastric acid response to hypoglycemia as compared to insulin alone, but the difference was not significant. In subjects allowed to sleep, this reduction was marked and gastric acid output was significantly lower than in both other series. These findings suggest that sleep and drowsiness, rather than bromazepam itself, cause inhibition of insulin-induced gastric secretion.