Resveratrol reduces electrical remodeling in atrial fibrillation by down-regulating microRNA-21 in neonatal rat atrial myocytes

AIM: To detect the effects of resveratrol (RSV) on the expression of microRNA-21 (miR-21) in primarily cultured neonatal rat atrial myocytes with electric remodeling induced by rapid electrical stimulation (RES). Furthermore, to find out the possible mechanism of miR-21 regulating electrical remodeling. METHODS: The neonatal rat atrial myocytes were isolated by double-enzyme (trypsin and collagenase I) digestion and differential adhesion method. The atrial fibrillation (AF) model was induced by RES. Atrial myocytes were randomly divided into 4 groups:control group, RSV group, RES group, and RSV+RES group. To further detect whether RSV regulated electric remodeling by miR-21, except the 4 groups, we add miR-21 over-expression group and miR-21 inhibitor group:RES+negative control (NC) group, RES+miR-21 mimics group, RES+miR-21 mimics+RSV group, RES+miR-21 inhibitor group, and RES+miR-21 inhibitor+RSV group. The optimal concentration and pretreatment time of resveratrol were determined by CCK-8 assay. The expression of miR-21 and the mRNA expression of L-type calcium channels CACNA1C and CACNB2 in atrial myocytes were detected by qPCR. The protein expression of L-type calcium channels Cav1.2 and Cavβ₂ in the atrial myocytes was analyzed by Western blot. RESULTS: The expression of miR-21 in RES group was significantly increased compared with control group, while preconditioning with RSV decreased the expression of miR-21. Compared with RES+miR-21 mimics group, the expression of miR-21 in RES+miR-21 mimics+RSV group was significantly decreased. Meanwhile, the mRNA expression of CACNA1C and CACNB2, and the protein levels of Cav1.2 and Cavβ₂ were increased (P<0.05). Compared with RES group, the expression of miR-21 in RES+miR-21 inhibitor group and RES+miR-21 inhibitor+RSV group was decreased, while the mRNA expression of CACNA1C and CACNB2, and the protein levels of Cav1.2 and Cavβ₂ were increased. However, no difference of the expression of miR-21, the mRNA expression of CACNA1C and CACNB2, and the protein levels of Cav1.2 and Cavβ₂ among RSV+RES, RES+miR-21 inhibitor and RES+miR-21 inhibitor+RSV groups was observed (P<0.05).CONCLUSION: In AF model induced by RES, RSV may reduce electric remodeling by inhibiting the expression of miR-21 and regulating the downstream target genes.     

Mitochondrial reactive oxygen species and atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Mitochondrial oxidative stress is supposed to contribute to development, progression and self-perpetuation of AF. Reactive oxygen species (ROS) is the major molecule mediating mitochondrial oxidative stress damage. ROS can alter the redox status of various molecular targets, which quite specifically leads to functional alterations of ion channel activity or activation of a variety of redox sensitive signal transduction pathways. Eventually, it leads to atrial electrical remodeling and promotes the development of AF. Therefore, mitochondrial oxidative stress pathways may be a new target for the therapy of atrial fibrillation.     

Prevalence and factors associated with initial and subsequent shockable cardiac arrest rhythms and their association with patient outcomes in dogs and cats undergoing cardiopulmonary resuscitation: A RECOVER registry study

Objective

To report the prevalence of initial shockable cardiac arrest rhythms (I-SHKR), incidence of subsequent shockable cardiac arrest rhythms (S-SHKR), and factors associated with I-SHKRs and S-SHKRs and explore their association with return of spontaneous circulation (ROSC) rates in dogs and cats undergoing CPR.

Design

Multi-institutional prospective case series from 2016 to 2021, retrospectively analyzed.

Setting

Eight university and eight private practice veterinary hospitals.

Animals

A total of 457 dogs and 170 cats with recorded cardiac arrest rhythm and event outcome reported in the Reassessment Campaign on Veterinary Resuscitation CPR registry.

Measurements and Main Results

Logistic regression was used to evaluate association of animal, hospital, and arrest variables with I-SHKRs and S-SHKRs and with patient outcomes. Odds ratios (ORs) were generated, and significance was set at P < 0.05. Of 627 animals included, 28 (4%) had I-SHKRs. Odds for I-SHKRs were significantly higher in animals with a metabolic cause of arrest (OR 7.61) and that received lidocaine (OR 17.50) or amiodarone (OR 21.22) and significantly lower in animals experiencing arrest during daytime hours (OR 0.22), in the ICU (OR 0.27), in the emergency room (OR 0.13), and out of hospital (OR 0.18) and that received epinephrine (OR 0.19). Of 599 initial nonshockable rhythms, 74 (12%) developed S-SHKRs. Odds for S-SHKRs were significantly higher in animals with higher body weight (OR 1.03), hemorrhage (OR 2.85), or intracranial cause of arrest (OR 3.73) and that received epinephrine (OR 11.36) or lidocaine (OR 18.72) and significantly decreased in those arresting in ICU (OR 0.27), emergency room (OR 0.29), and out of hospital (OR 0.38). Overall, 171 (27%) animals achieved ROSC, 81 (13%) achieved sustained ROSC, and 15 (2%) survived. Neither I-SHKRs nor S-SHKRs were significantly associated with ROSC.

Conclusions

I-SHKRs and S-SHKRs occur infrequently in dogs and cats undergoing CPR and are not associated with increased ROSC rates.     

Effect of spironolactone on hyperthyroxine-induced atrial fibrillation and atrial remodeling in rabbits

AIM: To detect the effect of spironolactone on hyperthyroxine-induced atrial remodeling. METHODS: New Zealand rabbits were divided into control group (C), hyperthyroxine group (H) and spironolactone group (S). Thyroxin was given to the rabbits in group H and group S by intraperitoneal injection for 4 weeks, and then spironolactone was given in group S by gavage for 2 weeks. Atrial fibrillation (AF) was induced by "burst" stimulation after administration. The inducing rate of AF and atrial effective refractory period (AERP) were tested by intra-cardiac electrophysiologic instrument. The expression of AF-related Ca²⁺ channel (Cav1.2), K⁺ channels (Kv1.5 and Kv4.3) and connexins (Cx40 and Cx43) at mRNA and protein levels was detected by real-time PCR, immunohistochemistry and Western blot. RESULTS: Spironolactone reduced the inducing rate of AF. No significant difference of AERP between group H and group S was observed (CONCLUSION: Spironolactone attenuates the hyperthyroxine-induced atrial remodeling in rabbits, and reduces the susceptibility of the myocardium to AF.     

Expression of MPO,MMP-2 and MMP-9 in atrial myocardium of rabbit atrial fibrillation model

ATM: To investigate the expression of myeloperoxidase (MPO), matrix metalloproteinase (MMP)-2 and MMP-9 in the atrial myocardium, and their potential effects on atrial structural remodeling in a rabbit atrial fibrillation (AF) model. METHODS: The sternotomy was performed and the pacing electrode was fixed to the left atria of 20 New Zealand white rabbits. The animals were randomly divided into 2 groups:rapid atrial pacing (RAP) group and sham group. The rabbits in RAP group were subjected to RAP for 3 weeks. The structure and function of the atria and ventricle were analyzed by echocardiography. Atrial burst stimulation was performed to test AF inducibility. The atrial fibrosis was evaluated by Masson trichrome-staining. The mRNA and protein levels of MPO, MMP-2 and MMP-9 were detected by RT-qPCR and Western blot. RESULTS: After 3 weeks of RAP, obvious left atrial enlargement and dysfunction were observed, but almost no change of left ventricular diameter and function was found in RAP group compared with sham group. AF inducibility, atrial interstitial fibrosis and the mRNA and protein levels of MPO, MMP-2 and MMP-9 were all significantly increased in RAP group compared with sham group. CONCLUSION: Obvious atrial structural remodeling is found in the rabbit AF model induced by sustained RAP, and the up-regulation of MPO, MMP-2 and MMP-9 may be the potential molecular mechanism of atrial structural remodeling.     

Persistent atrial standstill in a cat

A domestic shorthaired cat was presented with a 1-month history of cardiomegaly and recurrent chylothorax. The heart rate was 130 beats/min and no P waves were present on a surface electrocardiogram. Thoracic radiographs and an echocardiogram demonstrated severe biatrial dilatation, pleural effusion and restrictive pleural disease. Permanent atrial standstill was suspected. Pleurocentesis was performed and therapy was started with enalapril, frusemide and aspirin. Intracardiac electrograms revealed no atrial activity, and atrial pacing failed to elicit atrial or ventricular depolarisations. The patient was euthanased. Necropsy showed severe atrial wall thinning with marked cardiocyte loss. Persistent atrial standstill is a rare disease in the cat. Clinical signs may have been due to loss of atrial function, ventricular diastolic dysfunction, bradycardia, neurohormonal activation and reduced atrial natriuretic peptide plasma concentrations.     

珍珠宁心汤联合胺碘酮治疗心房颤动的近期疗效观察

目的 观察中药珍珠宁心汤联合胺碘酮治疗心房颤动的疗效.方法 60例心房颤动患者随机分为胺碘酮组(30例)和珍珠宁心汤联合胺碘酮组(简称宁心汤组,30例),1个月后复查动态心电图、心率变异性和心脏电生理检查.结果 胺碘酮组、宁心汤组的有效率差异无统计学意义(P＞0.05).宁心汤组的心率变异性参数比胺碘酮组明显缩短(P＜...     

糖尿病患者治疗前后血浆心钠素的检测及其临床意义

本文对65例糖尿病(DM)患者的血浆心钠素(ANF)含量作了检测,结果表明治疗前ANF含量为81.7±31.0pg/L,显著低于正常人95.7±18.1pg/L(P<0.05)。治疗前后ANF与胰岛素(INS)水平变化呈正相关(r=0.4131.P<0.0005),与血糖(FBG)水平变化呈负相关(r=-0.3781,P<0.0005),与C-肽(C-P)水平变化无相关(r=0.0610,P>0.50),提示测定ANF水平对DM的疗效观察有一定的临床价值。24例在胰高血糖素负荷后各时相中的ANF水平与相应INS、C-P、FBG水平无相关性。提示它们对调节ANF变化不起主要作用,推测ANF分泌可能同胰岛β-细胞功能和体内其它因素参与有关。