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Antiarrhythmic activity of Mexicord-Poland and Mexitil-Böehringer Ingelheim (D) was compared. In three models of experimentally evoked arrhythmia in animals, in used doses, both of examined preparations in the same degree prevented the occurrence of arrhythmia.
Electric stimulation and drug-induced ventricular fibrillation (VF), monophasic action potentials (MAP), and triggered activity were studied before and after administration of tetrahydroberberine (THB) in rabbits, rats or guinea pigs. At doses of 5, 10, and 20 mg.kg-1, i.v. THB increased the ventricular fibrillation threshold, and the BaCl2-induced VF was also prevented or terminated by THB in rabbits. Centrogenic VF induced by icv aconitine in rats was inhibited by pretreatment with THB in a dose-dependent manner, whereas VF induced by iv ouabain in guinea pig was inhibited to a lesser degree. For MAP, the duration at 90% repolarization (MAPD90) was prolonged remarkably, whereas the MAPD20, the MAP amplitude, and the maximal velocity of phase 0 were shortened or decreased slightly. The amplitudes of early afterdepolarization produced by cesium chloride (CsCl) were attenuated, while the cumulative threshold doses of CsCl for sustained ventricular tachycardia were elevated by THB. These results indicated that THB had an potent antifibrillatory effect, which might be attributed to its blockade of potassium, calcium, and sodium currents.
Myocardiocytes of mice were cultured. Action potentials were recorded with microelectrodes inside the cells. Scorpion venom from Buthus martensii Karsch 3.75 or 7.5 micrograms.ml-1 decreased the duration of action potential and all of the depolarization concerned parameters of myocardiocytes. The Vmax, TP, APA behaved apparently in a dosage-dependent way. Restoration happened after washing out. Tetrodotoxin 2.5 micrograms.ml-1 acted in a similar way. Nimodipine 3.0 micrograms.ml-1 led to a decrease in action potential duration. BaCl2 0.1 mmol.L-1 elongated the action potential duration, while decreased the parameters concerned with depolarization. These results indicate that the scorpion venom has Na+ channel blocking action.
I.P. injection (5g crude drug/kg) of water extract of Puhuang (Typha orientalis) to S.D. rats can prevent ventricular fibrillation and sudden death caused by isoproterenol and also arrhythmia induced by the infusion of BaCl2. Water extract of Puhuang can clearly increase the survival rate and also raise the dosage of BaCl2 infusion necessary to cause the death of animals.
Previous studies have reported that enhanced antiarrhythmic effects occur when agents that prolong repolarization are combined with agents that block the sodium channels. The mechanism(s) of this interaction have not been elucidated. In this study, the interactions between the prolongation of action potential duration (APD) by a potassium channel blocker and the reduction in the maximal upstroke velocity of phase 0 of action potential (Vmax) by sodium channel blockers were investigated in guinea pig papillary muscle using conventional microelectrode techniques. Agents that produce selective electrophysiologic effects were chosen, including low concentrations of barium chloride (BaCl2), which selectively blocks the inwardly rectifying potassium current without effects on other repolarizing or depolarizing currents, O-demethyl-encainide (ODME), which blocks the activated sodium channel with slow onset/offset kinetics, and mexiletine, which preferentially blocks the inactivated sodium channel with rapid onset/offset kinetics. Mexiletine (4 x 10(-6) M) decreased Vmax from 195 +/- 29 V/sec at baseline to 180 +/- 26 V/sec (P < .05). Whereas BaCl2 (10(-5) M) prolonged action potential duration, it had no effect on Vmax. However, the addition of BaCl2 to mexiletine synergistically decreased Vmax from 180 +/- 26 V/sec with mexiletine to 166 +/- 18 V/sec (P < .05). ODME (3 x 10(-7) M) decreased Vmax from 179 +/- 17 V/sec at baseline to 133 +/- 15 V/sec (P < .01). However, the addition of BaCl2 to ODME did not produce a further decrease in Vmax as compared with ODME alone. In summary, a synergistic effect on Vmax was observed when BaCl2 and mexiletine were combined.(ABSTRACT TRUNCATED AT 250 WORDS)
AIM: To study the effects of acute restraint stress on ventricular electric stability (VES) and its mechanisms of action. METHODS: VES was evaluated both in vivo and in vitro by the changes of arrhythmogenic responses to icv or ip aconitine in rats and iv BaCl2 or adrenaline in rabbits following restraint stress for different durations. Pretreatments and the assay of heart-specific enzymes were made. RESULTS: The heart sensitivity to these drugs was promoted after stress for 2 h, but obtunded after stress for 8 h (the latency of ventricular arrhythmia to icv aconitine was shortened from 4.1 +/- 0.9 min in control rats to 2.9 +/- 0.9 min after stress for 2 h, P < 0.05; but prolonged to 9.3 +/- 3.8 min after stress for 8 h, P < 0.05). In Langendorff heart, the changes of VES induced by stress were similar to those in vivo, but to lesser degree. Pretreatment with adrenalectomy inhibited the descending phase of VES, while pretreatment with both aminophylline and vagotomy remarkably depressed the ascending phase at 8 h. In addition, the serum activities of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase and their isozymes, LDH1 and CK-MB, were elevated at 2 h, and rose continuously at 8 h. CONCLUSION: Acute restraint stress causes biphasic changes of VES. The initial decrease of VES was related to adrenal catecholamine release, whereas the following increase of VES was ascribed to adaptive decrease of cAMP and vagal activation. The changes of VES did not always parallel the injury of heart.
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Knowing long term total parenteral nutrition (TPN) can bring 12 micrograms/kg/day as barium contamination, we investigated the barium ability to give the same bone toxicity as observed in patients' underlying TPN. A preliminary study carried out on 21 rats allowed us to calculate the bioavailability of barium chloride (50%) with doses fixed at 1 mg/kg for the intravenous route and 10 mg/kg for the oral route. As it is very difficult to feed rats parenterally for more than 30 days, we decided to give barium chloride orally. Twenty rats received 48 micrograms/kg/day barium chloride during 4 months. The barium plasma and bone levels were not statistically different between the control group and the tested group. The femurs and tibias were removed for analysis, carried out by different fixation and coloration techniques. No anomalies could be detected in the treated group concerning main bone parameters that are disturbed in patients' underlying TPN.
Barium hydroxyapatite (Ba10(PO4)6(OH)2, Ba-HAp) was synthesized by a wet method using Ba(OH)2.8H2O and (NH4)2HPO4 as starting materials. The Ba-HAp obtained had a Ba/P atomic ratio of 1.76 and contained CO3 groups. The Ba-HAp was sintered at 1073 K for 12 hours. The sintered Ba-HAp had a three point bending strength of 29 MPa and Young's modulus of 27 GPa. Cytotoxicity of the sintered bodies and particles was tested using L-cells. The sintered Ba-HAp showed no cytotoxicity, and the cells were closely in contact with the surfaces of sintered Ba-HAp. Morphological observation of the cell around the Ba-HAp particles also showed no cytotoxicity. However, cell growth was inhibited by Ca adsorption on the Ba-HAp particles. These results suggested that the Ba-HAp had no cytotoxicity and can be applied as a bioactive X-ray opaque material.
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Human chromogranin B (hCgB), a soluble marker protein of neuroendocrine secretory granules, was fused to green fluorescent protein (GFP). Two GFP-mutants with different folding properties, S65T and EGFP, were used to produce two recombinant proteins, hCgB-GFP(S65T) and hCgB-EGFP, respectively. After transient expression only hCgB-EGFP elicited green fluorescence in the neuroendocrine cell line PC12. Pulse-chase experiments with [35S]sulfate followed by subcellular fractionation showed that hCgB-EGFP was sorted with high efficiency to immature secretory granules (ISG). Confocal microscopy revealed that fluorescent hCgB-EGFP colocalized largely with synaptotagmin, a membrane marker of secretory granules and synaptic-like microvesicles, and significantly with endogenous rat chromogranin B (rCgB), a soluble marker of secretory granules. Upon stimulation of transfected cells with 5 mM Ba2+ or by depolarization with 50 mM K+ hCgB-EGFP underwent regulated exocytosis. The dynamics of green fluorescent secretory granules beneath the plasma membrane (PM) of living PC12 cells were visualized by confocal microscopy. The majority of these vesicles did not move within 8.5 sec as if they were docked. In contrast, in NGF-induced cells most of the secretory granules beneath the somatic PM moved within the same time period whereas only little movement was observed in the neurites. These findings indicate that in differentiated PC12 cells the majority of the docking zones are not in the soma but are distributed along the neurites. In conclusion, the fusion protein hCgB-EGFP provides a powerful tool to study in real time vesicular traffic in the regulated pathway of protein secretion.
Hydroxyapatite (HA) ceramic and piezoelectric biological ceramic, hydroxyapatite and barium titanate (HABT), were implanted in the jawbones of dogs. Histological observation showed that, compared with HA ceramics, HABT promoted the growth and repair of the bone significantly, the tissue growth around the HABT ceramic was direction-dependent, the collagen arranged orderly and the bone grew orderly. The order growth of the bone increased the efficiency of osteogenesis on the surface of the implanted HABT ceramics.
Polymerised adhesive may serve as a temporary sealant on prepared dentine surfaces and may be used as a precursor to the final bonding of a resin restoration. This procedure may, however, have an adverse effect on the strength of the final bond. This study was undertaken on 40 extracted human molar teeth to assess the effect of delayed bonding on the shear bond strength of a composite resin luted with a luting resin to abraded dentine treated with the Scotchbond Multi-Purpose (SMP) Bonding System (3M). No significant difference (p = 0.969) could be demonstrated between shear bond strengths achieved after immediate and delayed bonding to the polymerised Scotchbond Multi-Purpose adhesive.
To evaluate the clinical suitability of a barium silicate-filled composite (TPH) for restoration of posterior teeth, 50 Class II restorations were restored in 36 patients. Restorations included 22 molars and 32 premolars. Cavity preparations were protected with calcium hydroxide or a resin-modified glass ionomer cement, or both. Enamel was etched for 30 seconds with 37 percent H3PO4. All dentin surfaces were treated with a dentin bonding system that was placed, cured, and restored in 2 microns increments. The restorations were finished using diamond burs, polishing points, and paste. Evaluation periods were at zero (50 restorations), 6 months (35 restorations), 1 year (31 restorations), and 2 years (29 restorations), using the USPHS System and M-L indirect scale. At zero time, 50 restorations were scored "a" in all categories by using two independent evaluators. After 6 months, 35 restorations were graded with one "a" in postoperative sensitivity. After 1 year, 31 restorations were evaluated with one additional "b" for marginal integrity. After 2 years, 2 additional "b" for marginal integrity and 1 "b" for surface staining were noted. No "c" was observed in any categories throughout this study. Wear analysis revealed, on average, 2 microns of wear after 6 months, 7.8 microns of wear after one year, and 10.3 microns of wear after 2 years.
The combined antiarrhythmic effect of ethmosin and ethacisin in various dose ratios was studied in conscious dogs with two-stage ligation of the coronary artery (after Harris). A 6:1 ratio was found to be optimal for manifestation of the antiarrhythmic effect. In such a ratio of the doses the antiarrhythmic effect of a combination of ethmosin and ethacisin is essentially higher than the activity of each component. On the grounds of these data a combined antiarrhythmic drug methacisin was developed. It possesses a broad spectrum of antiarrhythmic activity. The drug is effective on models of arrhythmias specific of class I, III, and IV antiarrhythmics. Metacisin does not change hemodynamics and activity of the heart. Study of metacisin pharmacokinetics showed that it possesses bioavailability twice that of ethmosin tablets taken separately and four times that of ethasicin.
The present study was undertaken to investigate the influence of captopril and enalaprilat--two different angiotensin converting enzyme (ACE) inhibitors--on experimental cardiac arrhythmias induced by barium chloride, ouabain or adrenaline. The research was carried out on rabbits. Captopril and enalaprilat were administered only once. Arrhythmias were evoked by three different doses of arrhythmogens: ED50 and two higher ones causing rhythm disturbances in 80-100% rabbits. The patterns of arrhythmias as well as their frequency and duration were evaluated on the basis of ECG examination. The results were subjected to statistic analysis. As a result of our research, we were able to establish that ACE inhibitors, when administered at a single dose, did not influence the patterns but changed the frequency and duration of barium chloride-, adrenaline- or ouabain-induced arrhythmias. Captopril and enalaprilat administered at a single dose decreased the frequency of barium chloride- or ouabain- but not adrenaline-induced arrhythmia. A single administration of captopril and enalaprilat limit the duration of arrhythmias caused by barium chloride, ouabain or adrenaline.
The influence of 21-day administration of captopril and enalaprilat on barium chloride and adrenaline-induced experimental arrhythmias was assessed. The experiments were performed on rabbits. Arrhythmias were evoked by two alternative arrhythmogen doses. The patterns of disturbances, their frequency and duration were evaluated on the basis of ECG examination. Antiarrhythmic properties of angiotensin converting enzyme inhibitors administered for 21 days were also compared with their effects after single administration. The results were subjected to statistic analysis. On the basis of the obtained results we were able to establish that repeated administration of enalaprilat decreases the frequency of barium chloride- and adrenaline-induced arrhythmias. Repeated administration of captopril and enalaprilat shortened the duration of adrenaline- and barium chloride-induced arrhythmias. Long-term enalaprilat administration was much more effective in preventing arrhythmias than its single dose, it also proved to be more efficient than either single or repeated administration of captopril.
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