The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

VALUE AND LIMITATIONS OF SINUS NODE FUNCTION TE.ST BY ATRIAL PACING IN SICK SINUS SYNDROME DIAGNOSIS

In order to evaluate the significance of the sinus node function test by transvenous atrial pacing in the diagno,sis of sick sinus syndrome (SSS), sinus node recovery time (SRT), co]rrected sinus node recovery time (CSRT) and total atrio- sinus and sino-atrial conduction time (SACT) are observed in 69 patients including non-SSS group 39 cases and SSS group 30 cases. According to our data, we suggest criteria for sinus node dysfunction as follows. SRT>1,400 ms and/or A-V junctional esca.pe before sinus recovery and;or secondary pause, CSRT>560 ms. total SACT>300 ms. With l item abnormal, the false positive rat.e in the non-SSS group is 7.7c7。 and the false negative rate in the S.SS group 3.30i" with 2 items abnormal, the false positive rate in the non-SSS group Oi and the false negative rate in the SSS grOiup 6.7'70. Atropine test results are compared with that of atrial pacing, 95.8To and 84.2% are compatible with each other in these 2 groups. In order to cut the use of invasive technic to the minimum, we propose performing the atropine test first. Only in those with unexplainable test results should the trial pacing test. be resorted to..     

Experimental Study on Gufusheng in Treatment of Steroid-Induced Ischemic Necrosis of Femoral Head in Rabbits

Objective： To explore.the mechanisim of compound Gufusheng in treatment of steroid-induced ischemic necrosis of femoral head （SINFH）. Thirty-two rabbits were randomly divided into a blank control group （n=12） and a model group （n=20）. The rabbits of the model group were established by intramuscular injection of prednisone acetate （0.32mg/kg/d） for 8 weeks, and 2 rabbits in each group were killed at the 6th and the 8th week respectively to investigate whether the model was successfully prepared. Then remainder in the model group was again randomly divided into group A （Gufusheng group, n=8） and group B （model group, n=8）, while the rest of rabbits in the blank group constituted group C （n=8）. The rabbits in group A were given Gufusheng Decoction （骨复生煎液） by intragastric perfusion, and the rabbits in group B and C were fed with normal saline. After treatment for 4 weeks, the serum insulin-like growth factor-1 （IGF-1） and tumor necrosis factor-~ （TNF-α） levels in the rabbits of the 3 groups were determined by radioimmunoassay （RIA）. The serum TNF-α decreased significantly and the IGF-1 level increased significantly in the Gufusheng group as compared with the model group （both P〈0.01）. Compound Gufusheng can prevent SINFH and promote repair of the tissue of necrosis of femoral head possibly via decreasing the TNF-α and increasing IGF-1 level.     

牛磺酸对兔心肌缺血再灌注后血液流变学的影响

Aim To investigate the protective effect of taurine on hemorheologic feature,we reproduced the ischemic reperfused myocardium in rabbits. Methods Twenty rabbits were divided into 2 groups. Group 1(control group) no treatment was given during the 45 min ischemia and 180 min reperfusion. Group 2 (Taurine group) 5 min before reperfusion, taurine was given to rabbits in the bolus of 140 g/kg body-weight. The blood samples were taken before ischemia and at the time of reperfusion for 180 min to be insected the fallowing parameters. Rusults Whole blood viscosity at the high or low sheer was deteriorited significantly(P＜0. 05) at the point of reperfusion for 180 min as compared with those before ischemia in control group, but those parameters were ameliorated in Taurin group as compared with those in control group at time of 180 min reperfusion.Condusion Tourin can improve the hemorheologic condition to protect ischemic reperfusion myocardium．     

Sinoatrial Node Electrogram Studies in Patients with Sick Sinus Syndrome

Sinoatrial node electrogram (SNE) was recorded successfully in recent years, using transvenous electrode catheter. Via SNE and intratrialelectrogram (IEG), one could measure sinoatrial conduction time(SACT) directly, observe sinoatrial node (SN) potential changes in cadiac cycles, diagnose some sinus arrhythmias which couldn't be confirmed by surface ECG. All these could offer accurate evidence for differential diagnosis of sick sinus syndrome (SSS). The authors recommend a modified method for the location of the electrode catheter, by which one can increase success rate of obtaining stable SNE. Using this method, the authors recorded SNE in 10 cases with SSS successfully.     

Dynamics of Interstitial Calcium in Rat Myocardial Ischemia Reperfusion Injury In Vivo简

Intracellular calcium overload is a key factor for myocardial ischemia reperfusion injury（IR）. However, there was no report for interstitial calcium concentration dynamics. We investigated the interstitial calcium dynamics in rat myocardial IR model in vivo. A microdialysis system was involved, and the time delay of the system and recovery time was introduced and tested with a fluids switching method. Twelve SD rats were divided into IR or control group. Myocardial IR was induced by ligating（20 min） then releasing（60 min） the suture underlying left anterior descending branch. Mycrodialyisis probe was implanted into the left ventricular myocardium perfusion area for occlusion. Dialysate samples were collected every 10 min. Dialysate calcium concentration was detected with an atomic absorption spectrophotometer. Recovery time for the microdialysis system was 20 min, and recovery rate was 16%. Dialysate calcium concentration showed no changes during ischemia, descended immediately after reperfusion, reached the lowest level（67% of baseline value） 20 min after reperfusion, then escalated slowly. Recovery time was an important parameter for mycrodialysis technique, and it should not be neglected and needed to be tested. Our data suggest that interstitial calcium concentration in rats with myocardial IR in vivo kept steady in ischemia, descended rapidly at the initial reperfusion, then rebounded slowly. In conclusion, we introduced the concept of recovery time for microdialysis and provided a simple testing method.     

Long-term efficacy and safety of very-low-dose amiodarone treatment for the maintenance of sinus rhythm in patients with chronic atrial fibrillation after successful direct-current cardioversion

Background Long-term maintenance of sinus rhythm after successful conversion of chronic atrial fibrillation （CAF）, often ameliorates patients＇ symptoms, reduces the risk of ischemic stroke and improves cardiovascular hemodynamics. This prospective study aims to evaluate the long-term efficacy and safety of very low-dose amiodarone （100 mg daily） for the maintenance of sinus rhythm after successful direct-current （DC） cardioversion in patients with CAF and rheumatic heart disease （RHD） post intervention. Methods This study was a randomized prospective trial. One day after successful DC cardioversion （remained normal sinus rhythm） in patients with CAF and RHD post intervention for more than six months and adequate anticoagulation, all were randomly administered either amiodarone 200 mg daily in group A or amiodarone 100 mg dally in group B. Results A total of 76 patients （40 men and 36 women） were examined from February 1998 to December 1999. The mean age of the patients was （664- 10） years, and the mean follow-up was （674-8） months （range 61 to 84 months）. Actuarial rates of the maintenance of sinus rhythm were similar in the two groups after 5 years of follow-up. Four patients （11%） in group A but none in group B experienced significant adverse effects that necessitated withdrawal of amiodarone. No death occurred during the study period. Conclusion A very low dose of amiodarone results in adequate long-term efficacy and is safe for maintaining sinus rhythm in patients with CAF and RHD post intervention after successful DC cardioversion.     

Electrophysiological effects of Chinese medicine Shen song Yang xin （SSYX） on Chinese miniature swine heart and isolated guinea pig ventricular myocytes

Background Shen song Yang xin （SSYX） is a compound of Chinese medicine with the effect of increasing heart rate （HR）. This study aimed to evaluate its electrophysiological properties at heart and cellular levels. Methods The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks （n=8 per group）. Cardiac electrophysiological study （EPS） was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential （AP）. Results SSYX treatment accelerated the HR from （141.8±36.0） beats per minute to （163.0±38.0） beats per minute （P=0.013） without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR （IHR）, but decreased corrected sinus node recovery time （CSNRT） and sinus atrium conducting time （SACT）. Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial （A）, atrioventricular node （AVN） and ventricular （V） effective refractory period （ERP）. In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration （APD） without change in shape of action potential. The shortening rates of APD30, APD50 and APD9o were 19.5%, 17.8% and 15.3%, respectively. The resting potential （Em） and the interval between the end of APD30 and APD90 did not significantly change. Conclusions The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.     

The changes of nitric oxide and hemorheology in steroid-induced avascular necrosis of femoral head

Objective： To explore the pathogenesis of avascular necrosis of femoral head （ANFH）, the early diagnosis index and the treatment effective index of ANFH in clinical practice. Methods： Twenty-four Japanese rabbits were divided into 2 groups： model group and control group. ANFH models were produced by intramuscular injection of large dosage of steroid to rabbits for 8 weeks. On the 4 th, 8 th week after the injection, two rabbits each time from each group were taken to observe the structure of femoral head by light microscope and scanning electron microscope. Four other stomach-empty rabbits from each group were also used to test the contents of Nitric Oxide （NO）, contents of the hemorheology indexes. Results： Compared with the control group, the rabbits in the model group exhibited osteoporosis of femoral head and more bone lacuna and more fat cells through light microscope. Through scanning electron microscope observation bone trabecula were broken and sunk, and collagen fibers on the surface of bone matrix became loosen and broken, more osteocyte had pyknosis, adipocyte in the medullary cavity were enlarged and subchondral arterioles and capillaries of the femoral head were pressed by adipocyte. Compared with the control group, the model rabbits contained less NO and obvious increase of the plasma viscosity （PV）, low blood viscosity （LBV）, erythrocyte hematocrit （HCT）, indices of erythrocyte rigidity （TK） and indices of erythrocyte aggregation （AI）, plasma fibrin level （PFL） （P〈0. 01） and an increase of erythrocyte electrophoresis rate （ERT） （P〈 0. 05）. High blood viscosity （HBV）, and erythrocyte sedimentation rate （ESR） were unchanged. Conclusion： The steroid-induced ANFH might be related to less NO and the abnormal hemorheology; and NO and hemorheology should be considered as an early diagnosis index for ANFH in clinical practice.     

Reliability of pressure cuff induced transient limb ischemia in conscious rabbits

Background The protective effects of transient limb ischemia （TLI） induced by several cycles of intermittent pressure cuff inflation and deflation for a period have been widely investigated,however the reliability of this protocol has not been clearly verified.Our study aimed to investigate the reliability of pressure cuff induced TLI in conscious rabbits.Methods Eight New Zealand rabbits were subjected to TLI without anesthesia.TLI consisted of 3 cycles of ischemia and reperfusion induced by inflating the cuff placed on the left lower limb to 200 mmHg for 5 minutes followed by deflating the cuff for 5 minutes.Skin color,pulse oxygen saturation （SpO2）,pulse rate （PR）,plethysmogram waveform （Pleth）,and ultrasound detection of the blood flow in the extremity distal to the ischemic segment were observed to confirm ischemia and reperfusion during TLI.The frequency of severe limb movement during TLI was also recorded to assess the amenability of this protocol in conscious rabbits.Results The skin color of the extremity distal to the ischemic segment changed from bright red to dark purple after inflating the cuff to 200 mmHg,and returned to normal after cuff deflation.Pleth,PR and SpO2 disappeared during ischemia and restored during reperfusion in the monitor.Blood flow of the left posterior tibial artery was completely blocked by a pressure of 200 mmHg during ischemia,and recovered immediately after cuff deflation.The frequency of severe limb movement in supine position was higher than that in prone position （P〈0.05）,but there was no severe limb movement that could result in disturbance to ischemia when the rabbits were placed in prone position.Conclusion Pressure cuff inflating to 200 mmHg for 5 minutes and deflating for 5 minutes is a reliable regimen to induce TLI in conscious rabbits.     

缺血后处理对家兔右冠状动脉缺血再灌注窦房结功能的影响

目的：观察缺血后处理对家兔右冠状动脉缺血再灌注窦房结传导时间及恢复时间的影响。方法：在体成年家兔右冠状动脉缺血再灌注模型动物随机分4组：正常对照组（cT）、缺血／再灌注（IR）组、缺血预处理（IprC）组、缺血后处理（IpoC）组。在不同时间测定各组心房快速起搏或程序电刺激后的窦房结传导时间（SACT）、恢复时间（SNRT）。结果：与CT组比较，各组各时间点SACT、SNRT值均增高；IprC组各时间点SACT、SNRT值较IR组均明显下降，IpoC组缺血期各时间点sNRT值较IR组无显著差异，而再灌注期各时间点SACT、SNRT值较IR组明显下降；IprC组较IpoC组缺血期各时间点SACT、SNRT值明显下降，而再灌注期各时间点SACT、SNRT值无明显差异。结论：IpoC与IprC可能具有类似的窦房结保护功能。     

升陷汤加味方对急性病态窦房结综合征兔心肌电生理的影响

目的观察升陷汤加味方对急性病态窦房结综合征(SSS)兔心肌电生理指标的影响。方法将30只实验兔随机分为升陷汤加味方高、中、低剂量组、心宝丸组及对照组和模型组,每组各5只。给以相应药物1周后,通过甲醛湿敷窦房结制作兔急性损伤SSS模型,观测兔心率(HR)、窦房结恢复时间(SNRT)、校正窦房结恢复时间(CSNRT)及窦房传导时间(SACT)。结果升陷汤加味方高、中、低剂量和心宝丸均能升高急性损伤SSS兔HR,其中升陷汤加味方高剂量组与心宝丸组作用相当,差异无统计学意义(P0.05);而升陷汤加味方中、低剂量组与心宝丸组比较,作用较弱(P0.05)。升陷汤加味方高、中、低剂量和心宝丸均能有效缩短SNRT、CSNRT、SACT指标,其中升陷汤加味方高剂量组与心宝丸组作用相当,差异无统计学意义(P0.05);而升陷汤加味方中、低剂量组与心宝丸组比较,作用较弱(P0.05)。结论升陷汤加味方对兔急性损伤SSS有预防与改善的作用,提示大气下陷、心阳不振可能是病态窦房结综合征的主要病机。     

益阳活血方对损伤兔窦房结组织保护的形态学研究

目的探讨中药复方益阳活血方对甲醛引起的兔窦房结组织损伤的保护作用。方法取60只大耳白兔,随机分为正常组,模型组,阿托品组,益阳活血方高、中、低剂量组,每组10只,除正常组不造模外,余各组采用甲醛加压注射渗透法建立兔窦房结组织损伤模型,模型稳定后开始给药,疗程(7 d)结束后取材,光镜、电镜下观察窦房结组织病理形态学变化。结果除正常组外,各实验组均有不同程度的窦房结细胞损伤。光镜下主要表现为细胞肿胀,炎性细胞浸润以及细胞坏死等病变,电镜下主要表现为线粒体肿胀,嵴断裂、减少,核膜不规则,核仁裂解,染色质边集等。对比各治疗组窦房结组织病理形态学改变可以看出,益阳活血方高剂量组优于中、低剂量组及阿托品组。结论益阳活血方对窦房结组织病理性损伤有明显的保护作用,可能是治疗病态窦房结综合征的机制之一。     

病窦康口服液对家兔窦房结急性损伤模型的影响

目的：研究病窦康口服液对家兔窦房结急性损伤的影响。方法：选用家兔50只，分为5组，即模型对照组、阿托品组、心宝组、病窦康低剂量组和高剂量组。实验组给予病窦康口服液，对照组给予阿托品、心宝、心得安等。结果表明：病窦康口服液对家兔可提高心率，改善窦房结功能，使起搏频率增快，从异位心律变为窦性心律。增强窦房结的传导性。结论：病窦康口服液可改善窦房的自律性。     

L-精氨酸对兔右冠状动脉缺血再灌注时窦房结功能及房室结传导有效不应期的干预作用

OBJECTIVE: To study the effect of L-arginine (L-Arg) on sinoatrial conduction time (SACT) and sinus node recovery time (SNRT) and atrioventricular nodal effective refractory period (AVERP) in the course of ischemia- reperfusion (IR) of the right coronary artery in rabbits. METHODS: Thirty-two rabbit models of ischemia-reperfusion of the right coronary artery were randomly divided into control group, IR+saline group, IR+L-Arg group and IR+ L-arginine-methyl ester (IR+L-NAME group, 8 rabits in each group. At different time points after ligation or loosening of the artery, SACT, SNRT and AVERP were measured respectively by fast pacing of the right atrium and programmed electrical stimulations. RESULTS: Compared with the control group, SACT, SNRT and AVERP of the other groups were all prolonged significantly P<0.01 . In comparison with IR+NS group, at each time point, SACT, SNRT and AVERP of IR+L-Arg group were decreased during ischemia and in the early phases of reperfusion, followed by elevation during the latter stages of the reperfusion, as were contrary to the changes in IR+L-NAME group. CONCLUSIONS: The longer duration of ischemia persists, the severer are the functional damages of the sinoatrial node. Adequate supply of L-Arg to the tissues during ischemia and the early stages of the reperfusion may alleviate the damages, but its administration in the latter stages of reperfusion might contribute to the contrary result.     

冠心病患者窦房结功能的初步报告

应用非侵入性经食管心房起搏法,测量了50例冠心病(CAD)、11例病态窦房结综合征(SSS)和54例正常人的窦房结恢复时间(SNRT),校正窦房结恢复时间(SNRTc),窦房结恢复时间指数(SNRTI)和窦房传导时间(SACT).结果显示冠心组或(和)27例右状动脉受累者与对照组之间差异无统计学意义.本文并讨论了CAD与SSS间的关系.     

L-精氨酸对兔右冠状动脉缺血再灌注时窦房结功能及房室结传导有效不应期的干预作用

目的 观察L-精氨酸(L-Arg)对兔右冠状动脉缺血再灌注(IR)窦房结(SAN)传导时间(SACT)和恢复时间(SNRT)及房室结(AVN)传导有效不应期(AVERP)的影响。方法 在体成年兔右冠状动脉缺血再灌注模型分4组正常对照组,IR(缺血90min,再灌注90min)+生理盐水组,IR+L-Arg组和IR+左型精氨酸甲酯(L-NAME)组。在不同时相分别测定各组心房快速起搏或程序电刺激后的SACT、SNRT和AVERP。结果 IR+L-Arg组缺血期及再灌注早期3项指标均有不同程度的下降,而再灌注后期升高;IR+L-NAME组结果却基本相反(P<0.01)。3组组内比,IR+L-Arg组和L-NAME组于缺血期与再灌早期3项指标均升高;再灌注后期,IR+L-Arg组无治疗意义甚至加重SAN和AVN损伤,而IR+L-NAME组3项指标下降。结论 随着缺血时间延长SAN功能损伤加重;早期再灌注损伤敏感;组织内适当补充L-Arg,于缺血期和再灌早期对SAN电生理功能和AVERP恢复是有益的,于再灌注后期可能加重损伤。     

甲醛致家兔窦房结损伤模型的建立

目的 建立甲醛诱导的兔窦房结损伤模型。方法 采用40%甲醛溶液损伤兔窦房结,检测心率、窦房传导时间、窦房结恢复时间和校正窦房结恢复时间等指标,比较不同损伤方法、损伤程度、损伤持续时间等,并采用阳性药对模型进行验证。结果(1)损伤方法:湿敷法可通过时间及面积大小控制损伤程度;滴注法创伤小,可通过甲醛量来控制损伤程度,但易造成窦房结周围组织损伤;(2)损伤程度和维持时间:心率下降百分率小于基础心率的30%时,模型维持时间小于7 d;下降至基础心率的30%~60%时,模型维持时间可达70 d;下降大于60%基础心率的模型动物死亡率较高;(3)阳性药物的验证:阿托品和心宝丸均增加窦房结损伤模型心率,改善窦房结功能的作用。结论 甲醛湿敷法建立兔窦房结损伤模型较滴注法可靠性更高,损伤程度宜将心率下降百分率控制在基础心率30%至60%之间,模型维持时间长且动物死亡率低。     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function,atrio-ventricular node function and hemodynamics

ObjectiveTo investigate the influences of urapidil and nicardipine on rabbit sinus function, atrio-ventricular node function and hemodynamics.MethodsThirty-two Angora's rabbits were selected and randomly divided into four groups. U1 group:urapidil 0.25 mg/kg; U2 group:urapidil 0.5 mg/kg; N1 group:nicardipine 10 μg/kg; N2 group: nicardipine 20 μg/kg. All these medicine were administrated within 30 seconds. Measurements were taken before and after the administration of urapidil or nicardipine for the following data: mean blood pressure(MAP), heart rate(HR), sino-atrial conduction time(SACT), maximal sinoatrial recovery time(SNRTmax) corrected sinus node recovery time(CSNRT), index of sinus node recovery time(SNRTI), Wenckebach A-V conduction frequency (WB), and P-R interval.ResultsSignificant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine. No significant changes could be found in the rest of the parameters. Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P < 0.01); the MAP decreased(P < 0.01) and the HR increased drastically(P < 0.01).ConclusionsNeither urapidil(0.25 mg/kg, 0.5 mg/kg) nor nicardipine(10 μg/kg, 20 μg/kg) has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function. Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.