ABSTRACT
OBJECTIVE To compare the effect of four 5-hydroxytryptamine type 4 (5-HT4) receptor agonists:cisapride,zacopride,macopride and 2-[1-(4-piperonyl) piperazinyl]-benzothiazole (BZTZ),on rat cardiac inward rectifier potassium channel (IK1)and heart rhythm.METHODS The whole-cell configuration of patch-clamp technique was used to record effects of 5-HT4 receptor agonists onIk1 in enzymatic dissociated rat ventricular myocytes or Kir2.1 transfected HEK 293 cells.Western blotting was used to observe the expression of Kir2.1 channel exposed 24 h to agents in ventricular myocytes.Langendorff-perfused hearts were perfused with four agents respectively for 30 min.The electrocardiogram was recorded simultaneously.RESULTS BZTZ,cisapride and mosapride 0.1-10 μmol· L-1 decreasedIk1 in a concentrationdependent manner.At the same concentration (1 μmol· L-1),BZTZ showed the most potent inhibition onIκ1 (P＜0.01),followed by cisapride.Mosapride showed slight inhibition efficiency.However,zacopride enhanced Iκ1 (P＜0.01).In Kir2.1 heterologous expression systems,zacopride activated Kir2.1 current (P＜0.01) while mosapride had no effect.In ex vivo Langendorff-perfused hearts,BZTZ and cisapride 1μmol· L-1 elicited singnificant rhythm disturbances,and the total of premature ventricular beats (PVB) were 159±28 and 61±13.50％ (4/8) (P＜0.05) and 25％ (1/8) of the hearts exhibited ventricular tachycardia (VT),while 37.5％ (3/8) and 12.5％ (1/8) of the hearts exhibited ventricular fibrillation (VF),respectively.Mosapride and zacopride had no side effects on heart rhythm.Zacopride also suppressed BZTZ-or cisapride-induced arrhythmias.BZFZ had the strongest proarryhthmic potency among the 5-HT4 agonists,followed by cisapride,mosapride and zacopride.CONCLUSION Iκ1 might be an independent risk factor for arrhythmogenesis and a new target for screening safe 5-HT4 receptor agonists and gastrointestinal prokinetic agents.
ABSTRACT
Objective To analyze the potential factors facilitating post-pyloric placement of spiral naso-jejunum tube in critically ill patients.Methods A retrospective study was carried out in patients requiring enteral nutrition (EN) from Apr 2005 through Dec 2011 in Intensive Care Unit (ICU).Severity of illness was assessed with APACHE Ⅱ score (acute physiology and chronic health evaluation Ⅱ).A selfpropelled spiral naso-jejunum tube was placed and observed for 24 hours.The forward movement and place of the tube tip was checked by bedside X-ray.The APACHE Ⅱ score,therapeutic measures,agents administered within 24 hours after tube insertion were recorded.The patients were divided into the success group and the failure group identified by bedside X-ray whether the tube tip entered into jejunum or not.Univariate analysis and multivariate Logistic regression analysis were used to find out the potential factors impacting on the success or failure in post-pyloric placement of naso-jejunum tube.Results A total of 508 patients composed of 337 male and 171 female,and aged (62.0 ± 19.2) years with APACHE Ⅱ score of (21.9 ± 7.3) were enrolled for study.The placement was successful in 205 (40.4％) of 508 patients.Univariate analysis showed that APACHE Ⅱ score ≥ 20,sedatives and analgesics,catecholamines,prokinetics,artificial airway and mechanical ventilation were potential factors facilitating the post-pyloric placement of naso-jejunum tube.Multivariate logistic regression identified that APACHE Ⅱ score ≥ 20,sedatives and analgesics and prokinetics were independent factors facilitating the post-pyloric placement of naso-jejunum tube.Conclusions The success rate of self-propelled spiral nasojejunal tubes insertion was relatively low.The prokinetics contributed higher success rate of naso-jejunum tube placement than factors of APACHE Ⅱ score ≥ 20,sedative and analgesic,catecholamine drugs,artificial airway and mechanical ventilation.There were no effects of age and gender on the placement of naso-jejunum tube.
ABSTRACT
OBJECTIVE: To calculate the colonic transit time (CTT) and to evaluate the effect of combined therapy of cisapride and lactulose on neurogenic bowel dysfunction in patients with chronic spinal cord injury. METHOD: This study was prospectively designed. Right (rCTT), left (lCTT), rectosigmoid (rsCTT), and total (tCTT) colonic transit times were measured using the radio-opaque marker technique in twenty patients with spinal cord injury (SCI group), of which mean age was 39 years (range: 13~67 years) and median duration after SCI was 15 months (4-252 months). Ten ambulatory stroke patients (mean age 49 years, median duration, 12 months) were also evaluated as control group. All CTTs in both groups were compared by unpaired Student's t-test. In SCI group, the therapeutic effect of combined administration of cisapride (10 mg p.o. t.i.d) and lactulose (134.0 g/100 ml, 30-45 ml per day p.o.) was statistically analyzed by paired Student's t-test. RESULTS: Total (p<0.0001) and segmental CTT (p<0.01) except right colon were significantly delayed in SCI group when compared to the control group. In SCI group, tCTT of non-ambulatory patients (n=13) and rCTT, lCTT, rsCTT and total CTT of ambulatory patients (n=7) were significantly decreased after the combined drug therapy (p<0.05). In ambulatory SCI patients, duration after injury showed negative correlation with tCTT (Pearson's correlation coefficient r = 0.8407, p=0.0178). CONCLUSION: Combined therapy of cisapride and lactulose can improve tCTT in SCI patients with neurogenic bowel dysfunction.