OBJECTIVETo investigate the vasodilating effects of pethidine, particularly in association with intracellular calcium.

METHODSAorta rings of Sprague-Dawley rats, with or without endothelium, were prepared in organ bath to measure the vascular tone. Pre-contractions by KCl (80 mmol/L) and phenylephrine (PhE) (10(-6)mol/L) were induced.

RESULTSPethidine did not alter the resting tension of aorta rings, but produced dose-dependent relaxation in KCl and PhE pre-treated aorta rings with or without endothelium. Pethidine did not change the caffeine-stimulated contraction, and still had similar inhibition in KCl pre-contracted aorta rings after pretreatment with ruthenium red. Pethidine decreased the contractile responses induced by PhE in Ca(2+)-free solution or by adding calcium into Ca(2+)-free solution.

CONCLUSIONPethidine could produce an endothelium-independent vasodilatation in KCl and PhE pre-contracted aorta rings, which is related to inhibition of Ca(2+)entry and IP3-sensitive Ca(2+) release in vascular smooth muscle.

Animals ; Caffeine ; pharmacology ; Calcium ; metabolism ; Male ; Meperidine ; pharmacology ; Potassium Chloride ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasodilator Agents ; pharmacology

Sedation allows patients to tolerate unpleasant endoscopic procedures by relieving anxiety, discomfort, or pain. It also reduces a patient's risk of physical injury during endoscopic procedures, while providing the endoscopist with an adequate setting for a detailed examination. Sedation is therefore considered by many endoscopists to be an essential component of gastrointestinal endoscopy. Endoscopic sedation by nonanesthesiologists is a worldwide practice and has been proven effective and safe. Moderate sedation/analgesia is generally accepted as an appropriate target for sedation by nonanesthesiologists. This focused review describes the general principles of endoscopic sedation, the detailed pharmacology of sedatives and analgesics (focused on midazolam, propofol, meperidine, and fentanyl), and the multiple regimens available for use in actual practice.
Analgesia ; Analgesics ; Anxiety ; Endoscopy ; Endoscopy, Gastrointestinal* ; Humans ; Hypnotics and Sedatives ; Meperidine ; Midazolam ; Pharmacology ; Propofol

Histological studies were carried out on the degranulation of mesenteric mast cells of albino rats in which excised pieces of rat mesentery were incubated in media containing morphine and meperidine hydrochloride. The following conclusions were obtained. 1. The experimental dose of 0.04mg./ml. of morphine hydrochloride in Tyrode solution for the incubated mesenteric pieces brought about the degranulation of mast cells. 2. The experimental dose of 0.04mg./ml. of meperidine hydrochloride in Tyrode solution for the incubation of the mesenteric pieces did not effect the cytological changes of the mast cells. 3. By the addition of metabolic inhibitor such as iodoacetic acid to the incubating medium the degranulation of the mast cells was remarkably inhibited for the group in which the incubation was carried out for 20 minutes. However, the inhibition of the degranulation of the mast cells due to the metabolic inhibitor was abolished after 30 minutes of incubation. Consequently the authors have demonstrated the effect of morphine hydrochloride in its ability to induce a degranulation of mesenteric mast cells in vitro.
Animal ; In Vitro ; Male ; Mast Cells/cytology ; Mast Cells/drug effects* ; Meperidine/pharmacology* ; Mesentery/cytology ; Mesentery/drug effects* ; Morphine/pharmacology* ; Rabbits

Animals ; Intestines ; cytology ; drug effects ; physiology ; Meperidine ; pharmacology ; Mice ; Mice, Inbred Strains ; Muscle, Smooth ; drug effects ; physiology ; Rabbits

OBJECTIVETo study the protective effect of early application of lytic cocktail on small intestine of severely scalded rats.

METHODSSixty-six male SD rats were divided into sham injury group (SI, n=6), scald group (S, n=30) and scald+lytic cocktail group (SL, n=30) according to the random number table. After anesthesia, rats in the latter 2 groups were inflicted with 30% full-thickness scald, while rats in S group were sham scalded with 37 degrees C water. Resuscitation was carried out by intraperitoneal injection with 2 mLxkg(-1)x%TBSA(-1) lactated Ringer's solution in all rats; meanwhile 12 mL/kg lytic cocktail [1 mL pethidine (50 mg/mL)+1 mL chlorpromazine (25 mg/mL)+1 mL promethazine (25 mg/mL)+125 mL saline] was hypodermically injected to rats in SL group, while 12 mL/kg saline was injected into rats in the other 2 groups. Samples of blood and small intestine were harvested from S and SL groups at post scald hour (PSH) 3, 6, 12, 24, 48 and from SI group at PSH 3, with 6 rats in each group at each time point. Pathological changes in intestine were observed, and the expression of intercellular adhesion molecule 1 (ICAM-1) and CD68 were determined with immunohistochemistry at PSH 24 for S and SL groups and at PSH 3 for SI group. Plasma levels of D-lactate, diamine oxidase (DAO), IL-1beta, TNF-alpha, IL-10 were determined with ELISA. Data were processed with one-way analysis of variance.

RESULTS(1) At PSH 24, mild hemorrhage, inflammatory cell infiltration and epithelial cell shedding were observed in small intestinal mucosa of rats in S group. Compared with S group, the intestinal villi of SL group were arranged regularly without obvious hyperemia and edema. (2) Expression levels of ICAM-1 and CD68 [(1.69+/-0.27)%, (0.80+/-0.09)%] in S group were significantly higher than those in SI group [(0.77+/-0.10)%, (0.30+/-0.05)%, with F value respectively 77.303 and 66.933, P<0.05 or P < 0.01] and SL group [(0.53+/-0.09)%, (0.32+/-0.06)%, with F value respectively 77.303 and 66.933, P values all below 0.01]. (3) D-lactate levels of rats in SL group were significantly lower than those of rats in S group at PSH 12, 24 (with F value respectively 20.936 and 19.854, P values all below 0.01), while DAO levels of rats in SL group were significantly lower than those of rats in S group at PSH 3, 12 (with F value respectively 21.930 and 11.342, P values all below 0.05). (4) The levels of IL-1beta and TNF-alpha in S group were significantly higher than those of SI group at each time point (P values all below 0.01). The levels of IL-1beta and TNF-alpha in SL group were significantly higher than those of S group at PSH 6, 12 and 24 (with F value respectively 96.517, 17.365, 79.715 and 21.328, 17.682, 28.424, P<0.05 or P<0.01). IL-10 level in SL group was higher than that in S group at each time point, and the differences were statistically significant at PSH 6 and 24 (with F value respectively 8.668, 19.634, P < 0.05 or P<0.01).

CONCLUSIONSEarly administration of lytic cocktail can attenuate edema and injury of intestinal mucosa in severely scalded rats. The mechanism may lie in that it can reduce the expression of ICAM-1 in intestinal mucosa, decrease the number of intestinal inflammatory cells and regulate the levels of inflammatory cytokines.

Animals ; Burns ; therapy ; Chlorpromazine ; pharmacology ; Drug Combinations ; Intestinal Mucosa ; metabolism ; pathology ; Intestine, Small ; metabolism ; pathology ; Male ; Meperidine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo observe the effects of morphine and pethidine on P-glycoprotein (P-gp) expression in mouse brain microvascular endothelial cells and investigate the role of nuclear factor-kappaB (NF-kappaB) signaling pathway in morphine-induced up-expression of P-gp.

METHODSThe mouse brain microvascular endothelial cell line (b.END3) was subjected to pre-incubation with NF-kappaB inhibitor PDTC (5 micromol/L) for 1 h followed by stimulation with morphine (1 microg/ml) or pethidine (1 microg/ml) for 24 h. The bEnd.3 cells were then collected for Western blotting for P-gp expression.

RESULTSA 24-h morphine stimulation induced an up-expression of P-gp in bEnd.3 cells by almost 200%. Pethidine in similar conditions did not affect P-gp expression in the cells. PDTC, the specific inhibitor of NF-kappaB, inhibited morphine-induced up-expression of P-gp in the cells.

CONCLUSIONMorphine can induce up-expression of endogenous P-gp in mouse brain microvascular endothelial cells. NF-kappaB signaling pathway is involved in the morphine-induced up-expression of P-gp.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain ; blood supply ; Cell Line ; Endothelial Cells ; drug effects ; metabolism ; Meperidine ; pharmacology ; Mice ; Morphine ; pharmacology ; NF-kappa B ; metabolism ; Signal Transduction ; drug effects

OBJECTIVETo investigate the effects of pethidine on electrophysiological properties of the isolated ventricular myocytes and the underlying mechanism.

METHODSLangendorff was applied to perfuse rat heart model and whole-cell current clamp and voltage clamp techniques were used.

RESULTSPethidine decreased heart rate (HR) in a concentration dependent manner and caused severe atrioventricular block (AVB) at >or=250 micromol/L. Pethidine reduced action potential amplitude and maximal rate of depolarization, prolonged action potential duration. Pethidine at 100 micromol/L decreased sodium currents (I(Na)), transient outward potassium currents (I(to)), delayed rectifier potassium currents (I(k)) and L-type calcium currents (I(Ca.L)) to (60.7+/-6.9)%, (55.4+/-5.6)%, (65.1+/-8.0)% and (67.4+/-10.1)% of control levels,respectively. These effects could be recovered by washout. Naloxone, an opioid receptor antagonist, could not abolish the effects of pethidine on ionic currents.

CONCLUSIONPethidine decreased HR and induced AVB, which may be related to the inhibition of I(Na), I(to), I(k) and I(Ca-L) of heart. The depression of cardiac currents is not mediated by opioid receptor.

Action Potentials ; drug effects ; Animals ; Heart ; drug effects ; physiology ; Heart Block ; chemically induced ; Heart Rate ; drug effects ; In Vitro Techniques ; Ion Channels ; antagonists & inhibitors ; Male ; Meperidine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid ; physiology

The purpose of the present study was to investigate the effect of meperidine on rat ventricular muscle. Cardiac function was assessed in Langendorff-perfused rat hearts and intracellular calcium level was recorded in enzymatically isolated rat ventricular myocytes using spectrofluorometric techniques. To explore the underlying mechanism, whole-cell configuration of patch-clamp technique was used to record L-type Ca(2+) current. The results showed that meperidine decreased the product of heart rate and left ventricular developed pressure (LVDP HR), maximal rate of the left ventricular pressure increase (LV +dP/dt(max)) and decrease (LV -dP/dt(max)), but increased left ventricular end-diastolic pressure in a dose-dependent manner (0-1000 micromol/L). Meperidine also produced a dose-dependent reduction in electrically induced [Ca(2+)](i) transient amplitude and an increase in diastolic [Ca(2+)](i) baseline level, but did not alter the caffeine (20 mmol/L) induced Ca(2+) release from intracellular ryanodine-sensitive Ca(2+) stores. Meperidine at 100 micromol/L inhibited L-type Ca(2+) current to 67.4 10.1% of control but did not affect the voltage dependency of activation and inactivation. The inhibitory effect of meperidine on Ca(2+) current could not be prevented by pretreatment with the opioid receptor antagonist naloxone. These data suggest that meperidine exerts a negative inotropic effect by inhibiting L-type Ca(2+) current. The lack of effect of naloxone implies that the action is independent of the opioid receptor.
Animals ; Calcium Channels, L-Type ; drug effects ; Depression, Chemical ; Dose-Response Relationship, Drug ; Heart Rate ; drug effects ; Male ; Meperidine ; pharmacology ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Ventricular Function, Left ; drug effects