Objective Exploring the effect of clodronate liposome depletion of left stellate ganglion macrophages on ventricular ar-rhythmias after acute infarction in Beagle dogs.Methods Twelve adult male Beagles were divided into clod and control groups,with the Control group receiving microinjections of phosphate-buffered saline in the left stellate ganglion(LSG)and the Clod group receiving clo-dronate liposome.After modelling of acute cardiac infarction,electrocardiograms were recorded,neural function and activity were meas-ured,heart rate variability scores were analysed,hematoxylin-eosin staining was used to observe pathological changes in cardiomyocyte tissues.Immunofluorescence staining was used to verify the clearance of macrophages by disodium clodronate liposomes and fluorescence quantitative polymerase chain reaction was used to detect the level of expression of nuclear factor-kappa B(NF-κB)-related genes in LSG.Results Ventricular arrhythmias were significantly reduced in the clod group,with statistically significant differences(P＜0.05),significant inhibition of post-infarction LSG overactivation,improvement of heart rate variability,no significant impairment of hematoxylin-eosin staining,significant reduction in macrophages,and decreased expression of genes related to the NF-κB pathway(P＜0.05).Conclusion Clodronate-liposomes improve post-infarction arrhythmias by depletion of left stellate ganglion macrophages.The thera-peutic effect may be through an inhibitory effect on the NF-κB signalling pathway.

Objective Exploring the effect of clodronate liposome depletion of left stellate ganglion macrophages on ventricular ar-rhythmias after acute infarction in Beagle dogs.Methods Twelve adult male Beagles were divided into clod and control groups,with the Control group receiving microinjections of phosphate-buffered saline in the left stellate ganglion(LSG)and the Clod group receiving clo-dronate liposome.After modelling of acute cardiac infarction,electrocardiograms were recorded,neural function and activity were meas-ured,heart rate variability scores were analysed,hematoxylin-eosin staining was used to observe pathological changes in cardiomyocyte tissues.Immunofluorescence staining was used to verify the clearance of macrophages by disodium clodronate liposomes and fluorescence quantitative polymerase chain reaction was used to detect the level of expression of nuclear factor-kappa B(NF-κB)-related genes in LSG.Results Ventricular arrhythmias were significantly reduced in the clod group,with statistically significant differences(P＜0.05),significant inhibition of post-infarction LSG overactivation,improvement of heart rate variability,no significant impairment of hematoxylin-eosin staining,significant reduction in macrophages,and decreased expression of genes related to the NF-κB pathway(P＜0.05).Conclusion Clodronate-liposomes improve post-infarction arrhythmias by depletion of left stellate ganglion macrophages.The thera-peutic effect may be through an inhibitory effect on the NF-κB signalling pathway.

Objective To investigate the effect of afferent blockade of visceral adipose tissue(VAT)on cardiac function and cardiac neural remodeling in rats after myocardial infarction(MI).Methods After 30 healthy SPF-grade male SD rats were subjected,12 of them were randomly divided into control group(n=6)and activation group(n=6).In the activation group,low-dose capsaicin(1 mmol/L)was used to activate VAT afferent nerves,while in the control group,an equal amount of normal saline was injected,and real-time blood pressure and heart rate were monitored for 30 min.The other 18 rats were randomly assigned into sham group(n=6),MI group(n=6),and high-dose capsaicin blockade group(n=6).The MI model was established by ligating the left anterior descending coronary artery.After MI modeling,the high-dose capsaicin blockade group was give 33 mmol/L capsaicin to block VAT afferent nerve,and the sham opera-tion group and MI group were injected with the same amount of normal saline.After 2 weeks,car-diac function was measured by echocardiography,infarct size was measured by TTC staining,heart rate variability was analyzed,and myocardial tyrosine hydroxylase(TH)was measured.The levels of myocardial superoxide dismutase(SOD)and malondialdehyde(MDA)were measured by biochemical methods.Results More significant changes in blood pressure and heart rate were observed in the activation group than the control group(P＜0.01).The MI group had obviously larger infarct size,higher LVEDD and LVESD,and increased myocardial TH density and MDA level,but lower LVEF and myocardial SOD activity than the sham group(P＜0.05).However,the infarct size,LVEDD(9.15±0.37 mm vs 10.1±0.85 mm),LVESD(6.33±0.40 mm vs 7.87±0.86 mm)were obviously decreased,while LVEF[(67.04±3.34)％vs(47.10±3.89)％]and myocar-dial FS[(33.26±2.50)％vs(20.81±2.14)％]activity were greatly increased in the high dose capsaicin group than the MI group(P＜0.05).Conclusion Activation of VAT afferent nerve can increase blood pressure and heart rate;while its blockade can reduce the infarct size,protect cardiac function and inhibit cardiac nerve remodeling in MI rats,possibly by reducing oxidative stress.

Objective:To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism.Methods:The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining.Results:Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP ( P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower ( P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group ( P all<0.05). Conclusions:TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

Objective To investigate the effect of renal denervation on cardiac function and sympa-thetic nerve remodeling in spontaneously hypertensive rats(SHR).Methods Sixteen SPF male SHRs were randomly and equally divided into renal denervation(RDN)group and sham operation group,and 8 SPF Wistar-Kyoto(WKY)rats served as the normotensive control group.Blood pressure and heart rate of each group were non-invasively recorded every two weeks.In 8 weeks after the RDN procedure,mean arterial pressure was recorded after carotid artery catheterization,and heart rate variability,including low-frequency power(LF),high-frequency power(HF),and LF/HF ratio,was detected with electrocardiography.Cardiac function was assessed using echocar-diography(ECG),with indicators such as left ventricular ejection fraction(LVEF),left ventricu-lar fractional shortening(LVFS),left ventricular end-diastolic diameter(LVEDD),and left ven-tricular end-systolic diameter(LVESD).HE staining was used to assess myocardial injury,while immunohistochemical staining was employed to detect myocardial tyrosine hydroxylase(TH)density.RT-PCR was performed to measure the mRNA expression of IL-1β and TNF-α.Results The SBP before surgery,as well as at 2,4,6,and 8 weeks post-surgery,and the mean arterial pressure(MAP)were significantly higher in the sham operation and RDN groups than the control group,while,the MAP in the RDN group at 2,4,6,and 8 weeks post-surgery was significantly lower than that in the sham operation group(P＜0.05).Compared with the control group,the sham operation group showed significant increases in LVEDD,LVESD,heart weight-to-body weight ratio,myocardial TH,LF and LF/HF ratio,and myocardial IL-1β and TNF-α expression,while HF,LVEF,and LVFS were significantly reduced(P＜0.05,P＜0.01).Compared with the sham operation group,the RDN group showed significant increases in LVEF[(83.32±2.34)％vs(75.33±2.46)％,P＜0.05],LVFS[(45.57±2.42)％vs(38.42±1.64)％,P＜0.05],and HF(66.73±2.33 vs 60.23±1.54,P＜0.01).Meanwhile,LVESD[(3.56±0.34)mm vs(4.33±0.36)mm,P＜0.05],LVEDD[(6.43±0.38)mm vs(7.23±0.42)mm,P＜0.05],heart weight-to-body weight ratio(3.52±0.16 vs 3.82±0.22,P＜0.05),myocardial TH(0.15±0.01 vs 0.19±0.02,P＜0.05),LF[(15.55±1.08)％vs(19.91±1.79)％,P＜0.01]and LF/HF ratio(0.23±0.01 vs 0.33±0.03,P＜0.01),and the mRNA levels of myocardial IL-1β(2.47±0.15 vs 3.12±0.18,P＜0.05)and TNF-a(3.15±0.21 vs 3.79±0.17,P＜0.05)were significantly reduced.Conclusion RDN can reduce blood pressure in SHR,improve cardiac structure and function,and inhibit cardi-ac sympathetic nerve remodeling,which may be through alleviating neuroinflammation.

Objective To investigate the effect of renal denervation on cardiac function and sympa-thetic nerve remodeling in spontaneously hypertensive rats(SHR).Methods Sixteen SPF male SHRs were randomly and equally divided into renal denervation(RDN)group and sham operation group,and 8 SPF Wistar-Kyoto(WKY)rats served as the normotensive control group.Blood pressure and heart rate of each group were non-invasively recorded every two weeks.In 8 weeks after the RDN procedure,mean arterial pressure was recorded after carotid artery catheterization,and heart rate variability,including low-frequency power(LF),high-frequency power(HF),and LF/HF ratio,was detected with electrocardiography.Cardiac function was assessed using echocar-diography(ECG),with indicators such as left ventricular ejection fraction(LVEF),left ventricu-lar fractional shortening(LVFS),left ventricular end-diastolic diameter(LVEDD),and left ven-tricular end-systolic diameter(LVESD).HE staining was used to assess myocardial injury,while immunohistochemical staining was employed to detect myocardial tyrosine hydroxylase(TH)density.RT-PCR was performed to measure the mRNA expression of IL-1β and TNF-α.Results The SBP before surgery,as well as at 2,4,6,and 8 weeks post-surgery,and the mean arterial pressure(MAP)were significantly higher in the sham operation and RDN groups than the control group,while,the MAP in the RDN group at 2,4,6,and 8 weeks post-surgery was significantly lower than that in the sham operation group(P＜0.05).Compared with the control group,the sham operation group showed significant increases in LVEDD,LVESD,heart weight-to-body weight ratio,myocardial TH,LF and LF/HF ratio,and myocardial IL-1β and TNF-α expression,while HF,LVEF,and LVFS were significantly reduced(P＜0.05,P＜0.01).Compared with the sham operation group,the RDN group showed significant increases in LVEF[(83.32±2.34)％vs(75.33±2.46)％,P＜0.05],LVFS[(45.57±2.42)％vs(38.42±1.64)％,P＜0.05],and HF(66.73±2.33 vs 60.23±1.54,P＜0.01).Meanwhile,LVESD[(3.56±0.34)mm vs(4.33±0.36)mm,P＜0.05],LVEDD[(6.43±0.38)mm vs(7.23±0.42)mm,P＜0.05],heart weight-to-body weight ratio(3.52±0.16 vs 3.82±0.22,P＜0.05),myocardial TH(0.15±0.01 vs 0.19±0.02,P＜0.05),LF[(15.55±1.08)％vs(19.91±1.79)％,P＜0.01]and LF/HF ratio(0.23±0.01 vs 0.33±0.03,P＜0.01),and the mRNA levels of myocardial IL-1β(2.47±0.15 vs 3.12±0.18,P＜0.05)and TNF-a(3.15±0.21 vs 3.79±0.17,P＜0.05)were significantly reduced.Conclusion RDN can reduce blood pressure in SHR,improve cardiac structure and function,and inhibit cardi-ac sympathetic nerve remodeling,which may be through alleviating neuroinflammation.