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1.
China Pharmacy ; (12): 1215-1219, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1030847

RESUMO

OBJECTIVE To explore in vitro dissolution and in vivo pharmacokinetics of Luteolin solid dispersion in Beagle dogs. METHODS The dissolution of Luteolin solid dispersion was investigated according to the second method (paddle method) of the “dissolution determination method” in the 2020 edition of Chinese Pharmacopoeia (Part Ⅳ). UPLC-MS/MS method was established to determine the concentration of luteolin in the plasma of Beagle dogs. Twelve Beagle dogs were randomly divided into luteolin group and Luteolin solid dispersion group, with 6 dogs in each group. They were given relevant medicine orally at the dose of 10 mg/kg luteolin. Blood was collected before medication (0 h), at 5, 10, 15, 30, 45 min and 1, 2, 4, 6, 8, 10, 12, 24, 48 h after administration. After protein precipitation with acetonitrile, the blood concentration of luteolin in Beagle dogs was determined by UPLC-MS/MS and the major pharmacokinetic parameters were calculated with non-compartmental models by using DAS 3.2.8 pharmacokinetic software. RESULTS The dissolutions of Luteolin solid dispersion in purified water and 0.1% sodium dodecyl sulfate solution was significantly higher than those of luteolin; the dissolution rate reached 95% in 0.1% sodium dodecyl sulfate solution for 120 minutes. The peak concentration (cmax) of luteolin in the Luteolin solid dispersion group of Beagle dogs was 5.62 times higher than the luteolin group, and the relative bioavailability was 348%. Compared with luteolin group, cmax and the area under the drug time curve of luteolin in the Luteolin solid dispersion group of Beagle dogs were significantly increased, while the apparent distribution volume was significantly reduced (P<0.05). CONCLUSIONS Luteolin solid dispersion can improve in vitro dissolution and bioavailability of luteolin in Beagle dogs.

2.
China Pharmacy ; (12): 925-930, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016713

RESUMO

OBJECTIVE To prepare tetrandrine (TET)-loaded chitosan(CS)-stearic acid (SA) nano micelles modified with folic acid (FA)( FA-CS-SA/TET nano micelles), characterize them and study the anti-inflammatory effect in vitro. METHODS FA- CS-SA/TET nano micelles were prepared by ultrasonic method; the preparation technology was optimized by orthogonal test and validation test was also performed with the mass ratio of FA-CS-SA to TET, ultrasound power and ultrasound times as the factors, using the comprehensive score of entrapment efficiency (EE), drug loading (DL) and particle size as evaluation index. FA-CS-SA/ TET nano micelles prepared by the optimal technology were characterized, and their release performance in vitro was investigated. RAW264.7 cells were used as subjects to investigate their anti-inflammatory activity in vitro. RESULTS The optimal preparation technology included that the mass ratio of FA-CS-SA to TET was 2∶1, ultrasonic power was 200 W, and the ultrasonic frequency was 200 times. The parameters of FA-CS-SA/TET nano micelles prepared by optimized technology included that EE was (98.86± 0.30)%, DL was (28.57±0.34)%, the average particle size was (227.0±9.4) nm, polydispersity index was 0.42±0.04, and the Zeta potential was(12.6±2.3)mV, respectively. The nano micelles were uniform in appearance and round in shape. The nano micelles were released quickly in 0.5% sodium dodecyl sulfate solution, with a cumulative release rate of (79.49±3.43)% within 72 hours, and its anti-inflammatory effect was stronger than that of TET raw materials. CONCLUSIONS FA-CS-SA/TET nano micelles are prepared successfully in the study, with good drug loading performance, uniform particle size, and good in vitro anti-inflammatory activity.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1029055

RESUMO

Heart failure is the end stage of many cardiovascular diseases and has a high morbidity and mortality. With the improvements of treatment, the survival of heart failure patients has been prolonged, but still some patients are repeatedly hospitalized due to deterioration of conditions and have poor prognosis, thus seeking new therapeutic options is required. Vericiguat is a novel oral soluble guanylate cyclase stimulator that enhances the cyclic guanosine monophosphate pathway by directly stimulating soluble guanylate cyclase through a nitric oxide-independent binding site and sensitizes soluble guanylate cyclase to endogenous nitric oxide by stabilizing the binding site. Large clinical trials have shown that vericiguat reduces the risk of readmission for heart failure, improves prognosis, and has been approved for use in patients with heart failure with chronically reduced ejection fraction. This article reviews the mechanism and related clinical studies of vericiguat in the treatment of heart failure.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993125

RESUMO

Objective:To identify the method to reduce X-ray exposure during ablation of atrial fibrillation (AF) by comparing the cryoballoon (CRYO) ablation and remote magnetic navigation (RMN) ablation.Methods:A retrospective analysis was conducted on 144 patients undergoing CRYO ablation (CRYO group) and 121 patients undergoing RMN ablation (RMN group) in our hospital. Entrance surface doses at reference points online, exposure time during procedure and outcomes were analyzed for different types of patients.Results:Compared with the RMN group, the procedure time for the CRYO group significantly decreased [(165.0±23.6), (97.8±18.4) min, t=26.05, P<0.001]. However, the entrance surface dose value [(232.3±130.7), (669.0±387.5) mGy, Z=-12.29, P<0.001] and X-ray exposure time [(8.1±3.1), (23.4±6.2) min, t=-24.57, P<0.001] increased significantly for the CRYO group. No significant difference was found between the two groups in the proportion of maintaining sinus rhythm during follow-up of patients (71.9%, 75.7%, P=0.618). Multiple regression analysis showed that obese patients, patients with non-paroxysmal AF and patients with variant pulmonary veins were associated with an increase in entrance surface dose values in the CRYO group ( t=5.47, 2.23, 3.39, P<0.05). The X-ray exposure time for the three types patients above in the CRYO group also increased ( t=2.87, 3.86, 3.25, P<0.05) in the CRYO group. However, only obese patients in the RMN group had an increase in entrance surface dose value ( Z=-4.15, P<0.001) and no increase in exposure time. For the three types of patients above, there was no significant difference in proportion of maintaining sinus rhythm between the CRYO group and the RMN group during follow-up ( P>0.05). Conclusions:Compared with RMN ablation, the radiation exposure of CRYO AF ablation significantly increased, especially in obese patients, patients with non-paroxysmal AF and patients with pulmonary veins variation. The use of RMN for these types of patients may reduce the radiation exposure without affecting the procedure outcomes.

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-868535

RESUMO

Objective:To compare the differences of fluoroscopy time and dose between HIS bundle pacing and right ventricle apex pacing.Methods:This study includes thirty patients undergoing HIS bundle pacing (HIS group) and 32 patients undergoing right ventricular apex pacing (RVA group). The fluoroscopy time and cumulative dose (CD) to patients during surgery were recorded and analyzed.Results:The operation time for patients in HIS group and RVA group were (76.8±13.1) and (66.0±10.8) min ( t=3.386, P<0.001), respectively. The fluoroscopy time was (698.2±113.7) and (293.3±63.9) s ( t=14.709, P<0.001) and the CD were (391.3±70.0) and (162.3±40.5) mGy ( t=13.694, P<0.001) in HBP group and RVA group, respectively. In comparison, the fluoroscopy time and CD for HIS bundle electrode implantation were (501.2±112.3) s and (279.9±65.0) mGy, respectively, significantly higher than in the case of RVA, where the values were (103.4±30.6) s and (57.3±13.8) mGy ( t=15.864, Z=-6.524, P<0.001). Conclusions:Compared with right ventricular apical pacing, the HIS bundle pacing takes longer operation time, leading to higher radiation dose, which should be prudently selected.

6.
Chinese Journal of Cardiology ; (12): 640-646, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-805712

RESUMO

Objective@#To investigate the impact of n-3 polyunsaturated fatty acid (n-3 PUFA) on function and expression of store-operated calcium channels (SOCC) in coronary artery smooth muscle cells (SMC) derived from diabetic rat.@*Methods@#A total of 180 healthy male Sprague-Dawley (SD) rats were randomly divided into normal group (N, n=45), placebo-treated diabetic group (D, n=45), lose dose n-3 PUFA treated diabetic group (DL, n=45) and high dose n-3 PUFAs treated diabetic group (DH, n=45). Streptozotocin-induced diabetic rat animal model was established by two consecutive intraperitoneal injections. After modeling, rats in group DL and DH were treated with 10 mg·kg-1·d-1 and 50 mg·kg-1·d-1 n-3 PUFAs respectively per gavage for eight weeks. After eight weeks, rat coronary artery SMC was isolated by enzyme digestion. Changes of cytosolic calcium concentration in coronary artery SMC were examined by calcium fluorescence imaging technique, coronary artery tension was detected by myograph system, and protein expressions of SOCC on coronary artery SMC were measured by Western blot.@*Results@#SOCC induced ΔF340/F380 of group N, D, DL and DH were 0.425±0.023, 0.838±0.037, 0.342±0.052 and 0.364±0.045 respectively, which was significantly lower in group N, DL, DH than in group D (P<0.05). SOCC induced changes of tensions were 0.94±0.09, 1.95±0.18, 1.35±0.24 and 1.01±0.18 in the group N, D, DL and DH, respectively, which was significantly lower in group N and DH than in group D (P<0.05). Protein expressions of STIM1, Orai1 and TRPC1 were significantly higher in diabetic rat coronary SMC than in group N (P<0.05). STIM1 protein expressions were significantly lower in group DL and DH than in group D, and Orai1 and TRPC1 protein expressions were similar among group.@*Conclusions@#Coronary artery tension, cytosolic calcium concentration and protein expressions of SOCC are higher in diabetic rat coronary artery SMC when compared with normal rats. n-3 PUFA intervention could downregulate the protein expression of SOCC, reduce cytosolic calcium concentration and coronary artery tension, and is protective to the diabetic injury in coronary artery.

7.
China Pharmacy ; (12): 2926-2931, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-817470

RESUMO

OBJECTIVE: To prepare insoluble anti-tumor drug-loading polymer micelles, and to increase inhibitive effect of insoluble anti-tumor drug. METHODS: Chitosan (CSO) and stearic acid (SA) were used to prepare blank micelles (CSO-SA), then modified with mPEG and folic acid (FA) to prepare PEG-CSO-SA and FA-PEG-CSO-SA. Characteristic functional groups of CSO-SA, PEG-CSO-SA and FA-PEG-CSO-SA were detected by infrared spectroscopy. The morphology of micelles was observed by transmission electron microscopy. The particle size and Zeta potential of micelles were measured by laser particle size analyzer. Osthole (OST) was used as the model drug and drug-loading micelles (FA-PEG-CSO-SA/OST) were prepared by dialysis. MTT assay was used to detect the inhibitory rate of FA-PEG-CSO-SA, OST solution and FA-PEG-CSO-SA/OST to human liver cancer cell HepG2. Half inhibitory concentration (IC50) was calculated. RESULTS: FA-PEG-CSO-SA was successfully prepared. CSO-SA, PEG-CSO-SA, FA-PEG-CSO-SA were oval in shape; particle sizes were (96.01±5.99), (112.93±1.06), (216.01±4.76) nm (n=3) and Zeta potentials were (39.30±1.75), (38.03±2.91), (15.17±2.10) mV (n=3), respectively. Encapsulation efficiency and drug-loading amount of OST in FA-PEG-CSO-SA were (84.47±2.07)% and (16.01±0.90)% (n=3), respectively. The inhibition rates of FA-PEG-CSO-SA to HepG2 cells were<20%. IC50 of OST solution and FA-PEG-CSO-SA/OST to HepG2 cells were (62.08±5.21), (27.49±0.50) μg/mL (n=3), respectively. CONCLUSIONS: Prepared FA-PEG-CSO-SA can significantly increase inhibitive effect of insoluble drug OST to HepG2 cells, and it is expected to become a new anti-tumor drug carrier.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-614582

RESUMO

Objective To investigate the effects ofdocosahexenoic acid (DHA) on large conductance Ca2+-activated K+ (BK) channels in normal retinal artery smooth muscle cells (RASMCs).Methods Cultured human RASMCs (6 th-8 th generations) were used to patch clamp experiment.The open probabihties (NP0) in BK channels with different concentrations (0.0,1.0,3.0,5.0,7.5,10.0 μmol/L) of DHA were recorded by patch clamp technique in single channel configuration.RASMCs were intervened by different concentrations (0.0,1.0,5.0 μmol/L) of DHA as control group,low and high doses of DHA groups,respectively.The protein expressions of β subunit of BK channels in RASMCs from three groups were measured by Western blot.Results The NP0 of BK channels were 0.044 4±0.001 2,0.081 2±0.004 2,0.209 0±0.006 1,0.310 5±0.005 3,0.465 0±0.007 8 and 0.497 7±0.014 5 with perfusate of 0.0,1.0,3.0,5.0,7.5,10.0 μtmol/L DHA.DHA activated BK channels in a dose-dependent manner (F=2.621,P<0.05).There was no significant difference in the protein expression of control group,low and high doses of DHA groups (F=1 1.657,P>0.05).Conclusion DHA can directly activate BK channels,no increasing in subunit expression of BK channels.

9.
China Pharmacy ; (12): 107-110, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-507833

RESUMO

OBJECTIVE:To prepare Baicalin monolithic osmotic pump tablets and investigate its in vitro drug release behavior. METHODS:Using accumulative release rate as evaluation index,baicalin solid dispersion was prepared to improve solubility,sin-gle factor test and orthogonal test were used to optimize preparation technology(the amount of penetrating agent and pore-forming agent,weight gaining of coating film) of monolithic osmotic pump tablets using baicalin solid dispersion as intermediate. Release rate and mechanism of samples prepared by optimized technology were investigated in 3 kinds of release medium (water,0.1 mol/L HCl,simulated gastric fluid). RESULTS:The optimal preparation technology was that penetrating agent sodium chloride was 30 mg;pore-forming agent polyethylene glycol 400 was 20% amount of excipient cellulose acetate;weight gaining of coating film was 2%. RSD of 12 h accumulative release rate was 1.06%(n=3)for 3 batches of Baicalin monolithic osmotic pump tablets pre-pared by optimized technology. 12 h accumulative release rate of them in 3 kinds of medium were similar to each other,being all more than 80%. Release equation was in line with zero-order drug release model (r=0.9985). CONCLUSIONS:Prepared Ba-icalin monolithic osmotic pump tablets after optimization can release drug at controlled rate.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-637666

RESUMO

Background Diabetic retinopathy (DR) is a common microvascular complications of the retina,retinal vascular smooth muscle cells of large conductance calcium-activated potassium channels (BK) is a major factor in regulating vasomotor and hemodynamic.Currently,functional changes of BK channel in retinal artery smooth muscle cells (RASMCs) and its role in DR were rarely reported.Objective This study was to investigate the early vascular damage mechanisms in DR by detecting the changes of BK channels current,calcium concentration and open probability (NP0) of BK channel with different calcium concentration in RASMCs of normal and diabetic rats.Method Fifty SPF SD 8-12 weeks old rats were randomly divided into normal control group and diabetic model group.Forty diabetic rats was intraperitoneally injected with 60 mg/kg streptozotocin to form type 1 diabetic model,10 rats (the normal control group) were injected sodium citrate solution with the same manner.Fluorescent probe was applied to detect calcium concentration in rat RASMCs;RASMCs were isolated by using enzyme digestion,and BK-channel electric currents and calcium concentrations in the RASMCs were measured by whole-cell patch clamp technique and fluorescence assay,respectively.The NP0 of BK channel was measured by single patch clamp technique.Results Diabetic models were successfully established in 36 rats with the success rate 90%.When stimulation voltage is greater than 60 mV,the current density of BK channel in RASMCs of diabetic model group decreased;when stimulating voltage was 100 mV,the BK channel currents of RASMCs in the normal control group and diabetic model group were (100±23) PA/PF and (50 ± 7) PA/PF,the difference was statistically significant (t =19.80,P < 0.05).After adding specific BK channel blocker African scorpion toxin 100 nmol,the BK channel current in the normal control group significantly reduced,and that in the diabetes model group was not significantly changed;the calcium ion concentrations in RASMCs were (123±11)nmol/L and (255± 10)nmol/L in the normal control group and diabetic model group,the difference was statistically significant (t =32.50,P<0.05).When stimulation voltage was 60 mV,with increasing calcium ion concentration,the NP0 of BK channel increased (F =15.28,P<0.05).Conclusions The electric current and NP0 of BK-channel are obviously reduced and the calcium concentration is evidently elevated in RASMCs of diabetic rats,suggesting that the abnormal of BK-channel is probably one of the important causes of retinal artery abnormal contraction in diabetic rats.

11.
Zhonghua Yi Xue Za Zhi ; 95(13): 1024-8, 2015 Apr 07.
Artigo em Chinês | MEDLINE | ID: mdl-26506716

RESUMO

OBJECTIVE: To explore the effects and activation mechanism of adenosine triphosphate (ATP) on large conductance calcium-activated potassium channel ( BK channel) in coronary artery smooth muscle cells. METHODS: Coronary smooth muscle cells were isolated by enzyme digestion from Sprague-Dawley rats. And BK currents were recorded by patch clamp technique in whole cell configuration. The effects of ATP on cytosolic calcium concentrations were examined by recording the changes of fluorescence intensity ratios. RESULTS: BK current densities were (137 ± 13) pA/pF and (179 ± 15) pA/pF before and after a perfusion of 1 mmol/L ATP (P < 0.05). The fluorescence ratios were 2.46 ± 0.08 and 4.04 ± 0.21 (P < 0.05) before and after 0.5 mmol/L perfusion. After incubating with purine receptor (P2Y1) blocker MRS2179, phospholipase C (PLC) blocker U73122 and inositol triphosphate (IP3) blocker 2-APB, the fluorescence ratios were 2.7 ± 0.06, 2.65 ± 0.12 and 2.69 ± 0.13 respectively. Compared with control group, all fluorescence ratios decreased after incubating with three blockers (P < 0.05). CONCLUSION: ATP may elevate intracellular calcium concentration via P2Y1-PLC-IP3 pathway consequently activating BK channel.


Assuntos
Músculo Liso Vascular , Trifosfato de Adenosina , Animais , Cálcio , Vasos Coronários , Coração , Canais de Potássio Ativados por Cálcio de Condutância Alta , Miócitos de Músculo Liso , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-466259

RESUMO

Objective To compare the X-ray radiation dose from atrial fibrillation (AF) ablation guided by magnetic navigation system (MNS) and manual procedure (CON).Methods 94 AF patients were randomly divided into MNS group (34 cases) and CON group(60 cases).The dose area product (DAP),cumulative radiation dose (CD),fluoroscopy time of patients,the X-ray exposure time and dose of operators were recorded and analyzed.Results The results from the patients in MNS group and CON group were CD values (0.54 ±0.45) and (1.61 ±0.89) Gy (t =2.44,P <0.05),DAP values (46.86 ±27.09) and (139.71 ±76.69) Gy·cm2(t =3.89,P <0.05) and fluoroscopy time (15.60 ±7.52) and (39.50 ± 8.82) min (t =1.96,P < 0.05),respectively.The X-ray exposure dose in both groups were (22.68 ± 6.87) and (62.74 ± 20.92) μSv (t =2.02,P < 0.05) for operation doctor (19.38 ± 5.64) and (49.42 ± 10.67) μ Sv (t =3.58,P < 0.05) for operation assistant and (18.98 ± 4.99) and (47.77 ± 13.65) μ Sv (t =3.17,P < 0.05) for nurse,respectively.The X-ray exposure time experienced in both groups were (11.48 ±7.59) and (30.50 ±14.82) min (t =2.75,P <0.05) for operation doctor,(8.96 ±5.88) and (24.49 ±9.09) min (t =4.20,P <0.05) for operation assistant and (8.33 ±6.35) and (22.99 ± 13.36) min(t =2.76,P < 0.05) for nurse,respectively.Conclusions Compared with manual procedure,the MNS applied in AF ablation has the potential to decrease X-ray exposure dose.

13.
Herald of Medicine ; (12): 1637-1639, 2015.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-484608

RESUMO

Objective To investigate the optimal condition for transforming alkanna tinctoria pigment into shikonin. Methods Transformation rate of shikonin served as index. Transformation temperature, time, ratio of 2% NaOH to alkanna tinctoria pigment (v/w) was optimized. Results With ratio of 2% NaOH to alkanna tinctoria pigment being 4.5 mL·mg-1, temperature 35℃ and the reaction time 4 h, the transformation rate reached the highest, and the average transformation rate was 64.86%. Conclusion This method is easy and simple, and suitable for industrialized production.

14.
Chinese Medical Journal ; (24): 1775-1781, 2014.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-248113

RESUMO

<p><b>OBJECTIVE</b>This review focuses on the role of the large conductance calcium-activated potassium (BKCa) channels in diabetic vascular complications.</p><p><b>DATA SOURCES</b>Relevant articles published in English or Chinese from 1981 to present were selected from PubMed. The search terms were "BKCa channels" and "diabetes". Important references from selected articles were also retrieved.</p><p><b>STUDY SELECTION</b>Articles regarding the role of BKCa channels in diabetic vascular complications and relevant mechanisms were selected.</p><p><b>RESULTS</b>The BKCa channels are abundantly expressed in vascular smooth cells and play an important role in regulation of vascular tone. Multiple studies indicated that the expression and function of BKCa channels are altered by different mechanisms in diabetic vascular diseases such as coronary arterial disease, cerebral arterial disease, and diabetic retinopathy.</p><p><b>CONCLUSION</b>BKCa channels may play an important role in diabetic vascular complications and may be an effective therapeutic target for relieving and reducing the burden of diabetic vascular complications.</p>


Assuntos
Humanos , Doenças Arteriais Cerebrais , Metabolismo , Doença da Artéria Coronariana , Angiopatias Diabéticas , Metabolismo , Retinopatia Diabética , Metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta , Metabolismo
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-450841

RESUMO

miRNAs (microRNAs) are small RNA which regulate gene expressions at the post-transcriptional level.Recently studies have suggested that miRNA is associated with the development of diabetes mellitus and its complications.This artcle reviews the regulation of miRNA in diabetes mellitus and its cardiovascular complications,and the biomarkers' value and application of miRNA in the treatment of diabetes mellitus,aiming to develop new insight for the diagnosis and treatment of diabetes mellitus.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-418581

RESUMO

Objective To evaluate the role of real-time three-dimensional transesophageal echocardiography(RT3D-TEE) in non-valvular atrial fibrillation with left atrial appendage(LAA) stunning after catheter ablation.Methods Clinical and echocardiographic variables were analyzed by univariate regression in order to investigate the relationship between the group of LAA stunning and others in 28 patients after catheter ablation.Results Univariate analysis revealed difference in persisting time of atrial fibrillation[(16.4 ± 11.6)weeks vs (21.3 ± 18.6) weeks,P <0.05],left atrial diameter[(43.4 ± 8.3) mm vs (47.6 ± 5.9) mm,P <0.05 ],left atrial emptying fraction (0.38 ± 0.04 vs 0.30 ± 0.09,P <0.05).LAA emptying fraction based on three-dimensional volume measurements had significant difference (0.20 ± 0.03 vs 0.12 ± 0.02,P < 0.001) between the group of LAA stunning and other cases.Conclusions LAA ejection fraction calculation by RT3D-TEE is feasible and more accurate than by clinical and other echocardiographic in LAA stunning after ablaton of atrial fibrillation.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-385716

RESUMO

Objective To investigate the effects of docosahexaenoic acid (DHA) on action potential (AP)and transient outward potassium channel (Ito) in rat ventricular myocytes in order to evaluate the anti-arrhythmia mechanism of DHA. Method The rat ventricular myocytes were isolated by using enzyme digestion method. AP and Ito of individual ventricular myocyte were recorded by using patch-clamp technique in whole-cell configuration at room temperature. The effects of DHA on AP and Ito were observed when it was applied in 0 μmol/L, 20 μmol/L, 40 μmol/L, 60 μmol/L, 80 μmol/L, 100 μmol/L and 120μmol/L separaterly. Results The 25%,50% and 90% of action potential duration (APD25, APD50 and APD90) were gradually prolonged with the escalation of concentration of DHA ( P < 0.05, n= 20). The effects of DHA of different concentrations on AP maximal velocity (Vmax), AP amplitude (APA) and AP overshoot (OS) did not produce significantly different results (P > 0.05, n= 20). The degree of blockade of Ito was concentration-dependent as different concentrations of DHA were applied, and as the concentration of DHA was escalated, the I-V curves went downwards, the stably inactivated curves shifted to the lift, and the time taken for recovery from inactivation prolonged ( P < 0.05, n =20). However, the different concentrations of DHA did not produce different effects on stably activated curves ( P> 0.05). The Itos were blocked to (2.61 ± 0.26)%, (21.79±4.85)%, (63.11 ± 6.57)%, 75.52±7.26 ) %, (81.82 ± 7.63) % and (84.33 ± 8.25) % by the above given concentrations of DHA respectively under given potential equaling to + 70 mV( P < 0.05, n = 20), and the half-effect concentration (EC50) of DHA on Ito was(49.11±2.68) umol/L. Conclusions The effects of DHA on APD and Ito may be one of the anti-arrhythmia mechanism of DHA.

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