The effect of rabeprazole alone or in combination with H2 receptor blocker on intragastric pH: a pilot study.

BACKGROUND/AIMS: Proton pump inhibitors have been widely used in recent years. However, there are studies suggesting that proton pump inhibitors may not control the gastric acidity effectively during the night, especially in gastroesophageal reflux disease. It has therefore been suggested that H2 receptor blockers should be added to the therapy. The aim of our study was to evaluate the effects of proton pump inhibitors alone or in combination with H2 receptor blockers on gastric acidity with 24-hour gastric pH monitoring. METHODS: Esophagogastroscopy and 24-hour gastric pH monitoring were performed on 10 patients with dyspeptic symptoms. No patient had antacidity. All patients had erosive antral gastritis. Patients were randomized to two groups as either proton pump inhibitor therapy group (rabeprazole 20 mg/day, p.o.) or proton pump inhibitor + H2 receptor blocker therapy group (rabeprazole 20 mg/day, p.o. + famotidine 40 mg/day, p.o). After one month of treatment, 24-hour gastric pH monitoring was re-performed. RESULTS: Seven female and three male patients were enrolled into the study. The mean age was 51.1+/-11.56 years. All patients had antral erosive gastritis. Gastric pH was measured as less than 4 in 81.4% of the 24-hour period prior to rabeprazole treatment. With rabeprazole treatment this ratio decreased to 27.6% (p<0.05). These ratios were 86.3% and 4.55%, respectively, in the group that received combination therapy (p<0.05). CONCLUSIONS: Combination therapy with H2 receptor blockers and proton pump inhibitors seemed to control intra-gastric pH better than proton pump inhibitors alone. Use of H2 receptor blockers and proton pump inhibitors in combination to control intra-gastric pH is more beneficial.     

Prospective randomized trial for optimal prophylactic treatment of the upper gastrointestinal complications after open heart surgery.

BACKGROUND: Upper gastrointestinal bleeding is a lethal complication after open heart surgery. We designed a prospective randomized trial to test the efficacy of different antisecretory agents to prevent upper gastrointestinal disease after operation. METHODS AND RESULTS: A total of 210 patients were divided into 3 groups: group I had 70 patients who had mucosal protection (teprenone 150 mg/day), group II had 70 patients who had histamine2-receptor antagonist (ranitidine 300 mg/day), and group III included 70 patients who had a proton pump inhibitor (rabeprazole 10 mg/day). Gastric fiberscopy was used in all patients postoperatively during days 5 to 7. We compared the 3 groups in terms of endoscopic findings. Four patients (5.7%) had gastric bleeding complications in each of groups I and II; 2 died of coagulopathy. In group III no patients had gastric bleeding. The incidence of hemorrhagic gastritis was significantly higher in groups I (22.9%) and II (15.7%) than in III (2.9%) (p=0.0003). The incidence of active ulcers was also significantly higher in groups I (28.6%) and II (21.4%) than in III (4.3%) (p=0.0001). CONCLUSIONS: Early medication postoperative by a proton pump inhibitor was shown to be the most effective treatment and indeed might be described as mandatory to prevent upper gastrointestinal diseases after open heart surgery.     

Comparison of the therapeutic effects and acid suppression of H2-receptor antagonist and proton pump inhibitor in patients with gastric body ulcer--a prospective controlled trial]

We studied, the rate and the affecting factor of ulcer healing of patients with gastric body ulcer treated by H2-receptor antagonist (H2-RA) and proton pump inhibitor (PPI). Gastric acidity was also examined using 24 hr pH monitoring. No difference was observed between the affecting factor of ulcer healing and healing rate (94.7% and 94.9%) among the patients treated by H2-RA or PPI. The average time below pH3 during treatment with H2-RA or PPI were 17.4 +/- 4.3 hr and 23.0 +/- 1.5 hr, respectively. Acid suppression was superior in PPI treated group than in H2-RA group. From these findings, we concluded that H2-RA had sufficient therapeutic efficacy in treating gastric body ulcer.     

Low yield of endoscopy in patients with persistent dyspepsia taking proton pump inhibitors

BACKGROUND: Options for the evaluation of dyspepsia include a Helicobacter pylori test-and-treat strategy, empiric acid suppression, and initial endoscopy. The aim of this study was to determine the yield of endoscopy in patients in whom empiric therapy is unsuccessful compared with patients who received no empiric therapy and to identify factors associated with endoscopic findings. METHODS: A total of 100 patients with dyspepsia referred for endoscopy completed a questionnaire that included a query concerning response to therapy. EGD findings were compared in patients taking an H2-receptor antagonist, patients taking a proton pump inhibitor, and those not receiving empiric therapy. RESULTS: There were fewer endoscopic findings in patients being treated with a proton pump inhibitor compared with those taking an H2-receptor antagonist or those not receiving therapy (p < 0.01). Fewer proton pump inhibitor recipients had esophagitis or ulcer compared with patients in the no therapy group. Lack of symptom relief (<20%) by acid suppression was highly associated with a normal endoscopy (17/17). CONCLUSIONS: Patients with persistent dyspepsia being treated with a proton pump inhibitor have fewer endoscopic abnormalities compared with patients with dyspepsia taking an H2-receptor antagonist and those receiving no therapy. For patients with partial symptom relief, proton pump inhibitor therapy may mask endoscopic findings, particularly esophagitis. Interruption of proton pump inhibitors before endoscopy may increase diagnostic yield. Endoscopy is unlikely to yield a positive finding in patients who experience no symptom relief while taking a proton pump inhibitor or H2-receptor antagonist.     

Does antiplatelet therapy enhance myocardial salvage after coronary reperfusion?

The aim of this study was to test the hypothesis that either the cyclooxygenase inhibitor aspirin or the thromboxane A2 receptor antagonist sulotroban exerts a direct myocardial effect that enhances myocardial salvage afforded by reperfusion. Accordingly, 21 anesthetized dogs underwent suture occlusion of the left anterior descending coronary artery. At 2.5 h after occlusion, all dogs received intravenous streptokinase (20,000 U/kg body weight over 30 min) and were randomized to the following groups: group I (n = 7) received no additional treatment, group II (n = 7) received aspirin (5 mg/kg intravenously) and group III (n = 7) received sulotroban (10 mg/kg followed by 10 mg/kg per h intravenously). At 3 h after occlusion, the dogs underwent coronary reperfusion for the next 3 h. Myocardial infarct size as a percent of the hypoperfused zone was similar among dogs in group I (42 +/- 8%), group II (41 +/- 10%) and group III (45 +/- 11%). The incidence and the extent of myocardial hemorrhage were similar in all three study groups. Infarct size as a percent of the hypoperfused zone was significantly smaller in dogs without hemorrhage irrespective of treatment (35 +/- 9% versus 63 +/- 5%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

抑酸剂对脑手术应激病人的胃酸影响

目的：探讨抑酸剂质子泵抑制剂和Ｈ２受体拮抗剂对颅脑围手术期患者胃酸分泌的影响。方法：（１）３０例患者随机分组;Ｈ２受体拮抗剂泰胃美组,质子泵抑制剂洛赛克组和对照组。（２）所有病例均于手术前４小时监测胃内ｐＨ至７２小时;（３）分析颅脑手术患者术前,术中,术后胃内平均ｐＨ及ｐＨ〈４时间百分率。     

Combined thromboxane A2 synthetase inhibition and receptor blockade are effective in preventing spontaneous and epinephrine-induced canine coronary cyclic flow variations

The purpose of this study was to test the hypothesis that combined thromboxane A2 synthetase inhibition and receptor blockade is superior to either action alone in preventing cyclic flow variations in stenosed and endothelially injured canine coronary arteries. Forty-five dogs developed coronary cyclic flow variations after a plastic constrictor was placed around the left anterior descending coronary artery at the site where the endothelium was injured and received different interventions. In Group I, 17 dogs were treated with SQ 29,548, a thromboxane A2-prostaglandin H2 receptor antagonist. In Group II, 11 dogs received dazoxiben, a thromboxane A2 synthetase inhibitor. In Group III, R 68,070, a dual thromboxane A2 synthetase inhibitor and thromboxane A2-prostaglandin H2 receptor antagonist, was administered to 11 dogs. Group IV comprised six dogs that received aspirin before receiving R 68,070. Complete abolition of cyclic flow variations was achieved in 71% of dogs in Group I, 82% in Group II, 100% in Group III (p = 0.06 compared with Group I) and 50% in Group IV (p = 0.03 compared with Group III). Epinephrine was infused into dogs with abolished cyclic flow variations: all dogs in Group I had cyclic flow variations restored, 44% in Group II (p = 0.01 compared with Group I) and 64% in Group III (p = 0.04 compared with Group I). The plasma epinephrine levels required to restore cyclic flow variations were 2.2 +/- 0.5 ng/ml (control 0.04 +/- 0.01) in Group I, 8.7 +/- 4.5 ng/ml (control 0.05 +/- 0.02) in Group II and 7.4 +/- 2.6 ng/ml (control 0.07 +/- 0.02) in Group III.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protective effect of N2-mercaptopropionylglycine on rats and dogs liver during ischemia/reperfusion process

BACKGROUND: N2-mercaptopropionylglycine is a powerful super oxide synthesis inhibitor and has been tested as a preventive agent of metabolic and structural hepatic damage in the ischemia/reperfusion process. AIM: To analyze some effects of N2-mercaptopropionylglycine administration to animals of two species submitted to normothermic liver ischemia/reperfusion. MATERIAL AND METHODS: Twenty-two rats and 22 dogs were divided into four groups: group I: rats that received intravenous saline 0.9%; group II: rats that received 100 mg/kg of N2-mercaptopropionylglycine; group III: dogs that received saline intravenous 0.9% and group IV: dogs that received 100 mg/kg N2-mercaptopropionylglycine. RESULTS: Ten minutes after the saline or drug administration, each group was submitted to left lobe liver ischemia for 25 minutes followed by reperfusion. Biochemical studies 24 hours after reperfusion revealed a significantly lower elevation of transaminases in animals of groups II (AST = 271 +/- 182; ALT = 261 +/- 161 ) and IV (AST = 101 +/- 45; ALT = 123 +/- 89) when compared to the controls group: I (AST = 2144 +/- 966; ALT = 1869 +/- 1040 00) and III (AST = 182 +/- 76.51; ALT = 277 +/- 219), respectively. Histology study demonstrated a significantly minor aggression to animals of groups II and IV when compared to groups I and III, respectively. CONCLUSION: These results suggest a significant release of free radicals of oxygen in the process and that N2-mercaptopropionylglycine may have a significant protective effect on liver parenchyma when submitted to ischemia/reperfusion.     

Lansoprazole in the treatment of gastrooesophageal reflux disease in childhood

BACKGROUND: Acid suppressive therapy is the mainstay of pharmacologic treatment of gastro-oesophageal reflux disease. Use of proton pump inhibitors in children is still limited and has only included omeprazole in a few controlled studies. AIM: To determine efficacy of lansoprazole, a relatively new proton pump inhibitor, on symptoms and oesophagitis in a group of children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists. The required dose of the drug for inhibiting gastric acidity was also determined. PATIENTS AND METHODS: A series of 35 children (median age: 7.6 years, range: 3-15) with oesophagitis refractory to H2 receptor antagonists received a 12-week therapeutic course with lansoprazole. Prior to the study children underwent symptomatic and endoscopic assessment, oesophageal manometry and 24-hour intragastric and intra-oesophageal pH test. The latter was repeated after one week of therapy while patients were on treatment in order to monitor the degree of acid suppression and adjust the dose of the drug. Symptomatic assessment and endoscopy were repeated at the end of the trial RESULTS AND CONCLUSIONS: In 12 patients (group A), the initial dose of the drug was efficacious (1.3 to 1.5 mg/kg/day), whereas in 23 [group B) the initial dose (0.8 to 1.0 mg/kg/day) was increased by half because of insufficient inhibition of intragastric acidity (i.e., when the intra-gastric pH remained below 4.0 for more than 50% of the recording time). Nine patients in group A (75%) and 8 in group B (53.5%) healed (chi2: 3.6, p<0.05); 1 patient in group A [8.3%) and 7 in group B (30.5%) remained unchanged (chi2: 6.9, p<0.01); 2 patients in group A and 8 in group B improved and underwent a further month of therapy. The two groups did not differ as far as concerns baseline pH, endoscopic and clinical variables. In both groups, those patients failing to respond at the end of the trial showed a more impaired oesophageal motility than improved or healed patients. The drug was well tolerated and no significant laboratory abnormalities occurred. In children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists, a 12-week course of lansoprazole is effective both in healing oesophagitis and improving symptoms. An initial dose of 1.5 mg/kg/day of the drug is suggested. However, if during treatment, patients remain symptomatic the dose should be increased and a prolonged intra-gastric and intra-oesophageal pH test performed to evaluate the acid suppression efficacy of the adjusted dose. A short course of lansoprazole appears to be safe and well tolerated in paediatric age.     

Effect of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor antagonist on metabolism and contraction in ischemia-reperfused rabbit heart

The effect of angiotensin converting enzyme (ACE) inhibitor, temocaprilat and/or angiotensin II type 1 (AT1) receptor antagonist, CV-11974 on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, postischemic reperfusion of 60min was carried out. Temocaprilat and/or CV-11974 were administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDevP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: group I consisted of controls, group II was perfused with temocaprilat (10(-6)mol/L), group III was perfused with CV-11974 (10(-6)mol/L), and group IV was perfused with temocaprilat (10(-6)mol/L) in combination with CV-11974 (10(-6) mol/L). Groups II and III showed a significant (p<0.05) inhibition of an overshoot phenomenon of PCr during postischemic reperfusion compared with group I. Group IV also showed a more pronounced significant (p<0.01) inhibition of the overshoot of PCr during reperfusion compared with group I. Groups II, III and IV showed a significant (p<0.05) inhibition of the decrease in ATP during global ischemia (59+/-2, 54+/-3 and 54+/-7%, respectively) compared with group I (45+/-3%). Groups II and IV showed a significant (p<0.05) early recovery of ATP during reperfusion (81+/-2, 80+/-6%) compared with group I (71+/-3%) and group II (73+/-2%). Group IV showed no more significant recovery in ATP than group III. There were no differences in LVDevP, LVEDP and coronary flow among these groups. In conclusion, temocaprilat in combination with CV-11974 has significant potential for improving myocardial energy metabolism during both myocardial ischemia and reperfusion.     

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size limitation in conscious dogs

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size was studied in four groups of conscious dogs undergoing acute left anterior descending coronary artery occlusion. Group I received placebo for 48 hours before and for 24 hours after occlusion; group II received placebo before and nisoldipine (0.3 mg/kg orally every 6 hours) after occlusion; group III received nisoldipine before and placebo after occlusion; and group IV received nisoldipine before and after occlusion. Infarct size was quantified with the tetrazolium red staining technique. Infarcted ventricular mass was 24.5 +/- 6.6% (mean +/- SD) for group I (control), 21.4 +/- 4.4% for group II (p = NS against control), 13.9 +/- 4.5% for group III (p less than 0.05), and 14.1 +/- 4.0% for group IV (p less than 0.05). Post occlusion sudden death was 30% in non-pretreated dogs and 0% in pretreated dogs (p less than 0.001). We conclude that prophylactic oral treatment with nisoldipine decreases infarct size and lowers the incidence of sudden death in conscious dogs undergoing acute coronary occlusion.     

Complete arterial coronary artery bypass grafting versus conventional revascularization--early results

BACKGROUND: Complete arterial coronary artery bypass grafting (CABG) offers the potential to improve long-term results. However, an increased perioperative risk has been controversially discussed. New operative techniques (skeletonization of the ITA/ T-grafts/utilization of the radial artery (RA)) may decrease perioperative risk. We compared the outcome after conventional with that after complete arterial CABG. MATERIAL AND METHODS: Three consecutive groups of patients were analyzed. In group I (n = 50), CABG was performed using left ITA and vein grafts. The other two groups received complete arterial CABG with either both ITA's (group II; n = 52) or left ITA and RA (group III; n = 52). RESULTS: A mean of 3.9+/-0.8 (I) versus 4.2+/-0.8 (II) and 3.9+/-0.9 (III) anastomoses were performed per patient (ns). Mean operating time was significantly prolonged in group II (II: 252+/-54; p<0.0001; vs. I: 191+/-36; III: 203+/-33). Mean ischemic time was significantly prolonged in group II and III (II:65+/-20; p<0.0001; III: 68+/-16; p<0.0001; vs. I: 51+/-15). Mean bypass time (I: 83+/-23; II: 95+/-41; III: 91+/-21), the rate of postoperative complications and in-hospital mortality (I: n = 0; II: n = 2; III: n = 0; ns) showed no significant differences. Conclusions: Complete arterial CABG using modern surgical techniques is as safe as the conventional surgical approach using left ITA and vein graft.     

Effect of experimental diabetes on the protection by angiotensin blockers on nitric oxide deficient stroke in stroke-prone spontaneously hypertensive rats

Recently, we have shown that chronic administration of N-Nitro-L-Arginine Methyl Ester (L-NAME, an inhibitor of nitric oxide synthase) precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Angiotensin receptor antagonist (L-158,809) was shown to delay the onset of such stroke. In the present study, five groups of 4-week-old SHRSP were used. Three groups of SHRSP were made diabetic using streptozotocin (100 mg/kg i.p.). SHRSP from groups I (non-diabetic) and III (diabetic) chronically received L-NAME(0.5 g/L) and L-158,809 (20 mg/L) in saline to drink. Diabetic SHRSP (group C) received only saline to drink. SHRSP groups I and III developed stroke in 10+/-2 and 11+/-2 days. Average stroke-free period in groups II and IV was 18+/-2 and 29+/-2 days, respectively. Protective effect of streptozotocin-induced diabetes disappeared when SHRSP drinking L-NAME and L-158,809, also received subcutaneous injections of insulin. Present data suggest that experimental diabetes delays the onset of L-NAME-induced stroke in SHRSP and this protection is seen in the absence of renin-angiotensin system.     

Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury

AIM: To investigate the effect of shenfu injection on gastrointestinal microcirculation after myocardial ischemic-reperfusion (IR) injury in rabbits and probe into the mechanism. METHODS: Forty healthy flap-eared white rabbits were randomly divided into 4 groups: IR injury control group (groupⅠ), shenfu injection 5 mL/kg per h group (groupⅡ), shenfu injection 10 ml/kg per h group (groupⅢ) and shenfu injection 20 mL/kg per h group (groupⅣ). The four groups were treated with Lactated Ringer' s solution, shenfu injection 5, 10, and 20 mL/ kg per h were infused intravenously 30 min before experiment respectively. The values of hemodynamics [mean arterial pressure (MAP), heart rate (HR), gastric intramucosal partial pressure of carbon dioxide (PCO2), blood gas analysis and pH] were measured and compared with those before myocardial ischemia, 60 min after myocardial ischemia and 60, 90, and 180 min after reperfusion. RESULTS: The MAP, HR and gastric intramucosal pH were (70.50±4.50) kPa, (165±14) beats per min, 7.032±0.024 in group I 60 min after myocardial ischemia, which were significantly decreased compared with those before myocardial ischemia (88.50±9.75 kPa, 217±18 beats per min, 7.112±0.035, P < 0.05). The MAP, HR and gastric intramucosal pH were significantly decreased in group I 60, 90, and 180 min after reperfusion (61.50±5.25 kPa, 133±31 beats per min, 6.997±0.025) compared with those before reperfusion respectively (P < 0.05), whereas the values were insignificantly different in groupsⅡ,ⅢorⅣafter reperfusion, compared with those before reperfusion, and there were no significant differences between groupsⅡ,Ⅲ, andⅣafter reperfusion. CONCLUSION: Pre-infusion of shenfu injection has a protective effect on gastrointestinal microcirculation after myocardial IR injury in rabbits, in a dose independent manner.     

Inhibition of atherosclerosis by fish oil in cholesterol-fed rabbits

To evaluate the effects of dietary fish oil on cholesterol-induced atherosclerosis, 36 New Zealand rabbits in four groups were fed a 0.3% cholesterol diet for 10 weeks. One group served as control, whereas groups I, II and III received 1, 2 and 3 ml/day, respectively, of fish oil (Protochol, eicosapentaenoic acid, 180 mg, and docosahexaenoic acid [DHA], 120 mg/ml). The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the control group was 59 +/- 22%. The two higher dose fish oil groups showed a significant reduction in aortic lesions: group I (40 +/- 26%, p = NS), group II (18 +/- 11%, p less than 0.01) and group III (36 +/- 22%, p less than 0.05). Area of pulmonary artery lesions was significantly higher in the control group (48 +/- 22%) as compared with group I (15 +/- 13%, p less than 0.01), group II (4 +/- 3%, p less than 0.01) and group III (8 +/- 9%, p less than 0.01). The high cholesterol diet in the control group decreased bleeding time from 82 +/- 17 to 59 +/- 22 s (p less than 0.05). Groups II and III showed an increased bleeding time (62 +/- 15 to 84 +/- 17 s and 66 +/- 22 to 95 +/- 27 s; p less than 0.05, respectively). Fish oil did not significantly alter total serum cholesterol and high density lipoprotein (HDL) cholesterol. In group II triglyceride decreased from 128 +/- 22 to 64 +/- 25 mg/dl (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of intra-oesophageal and intra-gastric pH with proton pump inhibitors in patients with Barrett''s oesophagus

BACKGROUND: A significant percentage of patients with Barrett's oesophagus (BE) will continue to manifest abnormal intra-oesophageal pH profiles regardless of proton pump inhibitor (PPI) therapy. AIMS: We conducted a prospective study in order to determine whether a change in PPI therapy would alter intra-oesophageal and intra-gastric acid suppression in BE patients. PATIENTS: Seventeen Helicobacter pylori-negative BE patients (16 males, 1 female; mean+/-S.D. age, 63.5+/-13.2). METHODS: Twenty-four-hour pH monitoring was performed on omeprazole or lansoprazole, followed by repeat pH monitoring on rabeprazole at a dose titrated for symptom relief. Patients completed validated symptom and health-related quality-of-life (HRQL) surveys while on and off therapy. RESULTS: Ten (59%) of the 17 patients had abnormal baseline intra-oesophageal pH profiles. Oesophageal pH monitoring values on rabeprazole were abnormal in five out of five (100%) of the omeprazole cohort and three out of five (60%) of the lansoprazole cohort that had abnormal pH profiles on initial testing. Intra-gastric pH control was inadequate in BE patients on all PPIs; the mean percentage time with intra-gastric pH below 4.0 was 46% on omeprazole, 71% on lansoprazole and 51% on rabeprazole (p=0.25). All of the patients demonstrated the phenomenon of nocturnal acid breakthrough while undergoing PPI therapy. CONCLUSIONS: Change in PPI therapy did not alter intra-oesophageal or intra-gastric control in patients with BE.     

Effects of histamine H2-receptor antagonists and a proton pump inhibitor on the mucosal hydroxyproline content of ethanol-HCl-induced gastric lesions in rats.

We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion.     

Effect of the increase of the caloric load of a meal on gastric emptying of its solid and liquid phases

Caloric regulation of gastric emptying was mainly assessed with artificial liquid meals. We thus studied the effects of glucidic and lipidic caloric loads on gastric emptying of a solid-liquid meal (400 ml; 480 kcal), measured by an isotopic technique. Sixteen healthy subjects were separated in 3 groups; solutions of identical volume (400 ml) were added to the meal: water in group I (N = 6), glucose polymers (Caloreen; 400 kcal) in group II (N = 5), and triglycerides (Intralipide; 400 kcal) in group III (N = 5). Gastric emptying was dramatically slower in groups II and III than in group I, whatever the parameter considered. The magnitude of this caloric brake was identical for the 2 caloric loads tested and concerned both phases of the meal. Therefore, 3 h after the end of the meal, intragastric percentages of ingested liquids were 50 +/- 4 in group II, 52 +/- 5 in group III, vs 14 +/- 1 p. 100 in group I (p less than 0.001); for solids these percentages were 56 +/- 6 and 68 +/- 2 vs 11 +/- 3 p. 100 (p less than 0.001). In all groups, emptying of solids was slower than that of liquids, but the kinetics of this discrimination was modified by the increase of caloric load. The pyloric output of calories, estimated for the 3 h of the study was close to 2 kcal/min for the 3 groups studied. Thus, the 2 fold increase of the caloric concentration in groups II and III as compared to group I, did not modify the delivery rate of energy to small bowel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Right ventricular performance in patients with coronary artery disease.

While left ventricular (LV) performance in patients with coronary artery disease (CAD) has been extensively investigated, little attention has been given to right ventricular (RV) function in this disease. For this purpose, a new geometric model for RV volume has been developed and RV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI) and ejection fraction (EF) have been determined from biplane RV cineangiograms in 26 patients. Eight patients served as normal (control) subjects (group I). Eighteen patients with obstructive CAD comprised two other groups: six who had no significant disease of the right coronary artery (RCA) (group II) and 12 who had a high grade RCA lesion (group III). The mean values for EDVI, SVI and EF in group I were 76 +/- 11 ml/m2, 50 +/- 6 ml/m2, and 66 +/- 6%. The only significant difference between groups I and II was that SVI was lower in group II than in group I (P less than 0.01). No measurements in groups II and III were statistically different from each other. However, markedly subnormal values were found in group III (EDVI: 61 +/- 16 ml/m2, SVI: 33 +/- ml/m2 and ef: 52 +/- 7%); all values being significantly lower (SVI and EF: P less than 0.001; EDVI: P less than 0.05) than in group I. RV end-diastolic pressure was normal in all patients. These findings may related to 1) reduced RV compliance, 2) distorted LV geometry, 31 possible RV ischemia or 4) reduced Frank-Starling effect.     

Antihypertensive effect of enalapril in essential hypertension: role of prostacyclin

The effects of enalapril alone and in combination with the cyclooxygenase inhibitors sulindac and indomethacin on blood pressure (BP), plasma aldosterone, renin activity and converting enzyme activity were evaluated in 29 patients with mild to moderate essential hypertension, 26 of whom had low plasma renin activity. Patients were randomly assigned to one of three treatment groups. All patients underwent a 4-week placebo phase (phase I), then received enalapril (20 mg BID) for 4 weeks (phase II). In phase III, group I (n = 10) continued on enalapril alone; group II (n = 9) received sulindac 200 mg BID plus enalapril, and group III (n = 10) received indomethacin 50 mg BID plus enalapril, all for 4 weeks. Enalapril lowered BP significantly (mean supine BP 149/100 in phase I vs. 134/90 in phase II, p less than 0.05) without inhibiting aldosterone production. The BP effect was not blunted by concomitant administration of sulindac or indomethacin. Enalapril lowered converting enzyme activity to 25% to 30% of baseline and tended to increase renin activity. In the 10 patients who received indomethacin (group III), the effects of enalapril alone and enalapril plus indomethacin on urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin (PGI2), were examined. Enalapril increased urinary 6-keto PGF1 alpha in group III from 118 +/- 23 to 194 +/- 38 ng/g creatinine (p less than 0.05), while addition of indomethacin reduced 6-keto PGF1 alpha to basal levels (138 +/- 26 ng/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)