不同剂量瑞芬太尼对心内传导系统的影响

目的研究不同荆量瑞芬太尼对心内传导系统的影响。方法健康家兔24只,建立离体Langendofff心脏灌注模型,随机分为3组(n=8),A组：灌注正常的Krebs-Hensleit(K-H)液持续45min B组：用正常K-H液平衡灌流15min,再灌注含瑞芬太尼25ng／ml的K-H液20min;C组：含瑞芬太尼40ng／ml的K-H液灌注20min。各组于平衡灌流15min(基础值)、瑞芬太尼灌注20min(实验值)测定HR、SACT、SNRT、CSNRT、2：1B、OTC、p-R间期、QRS问期。结果25ng／ml、40ng／ml的瑞芬太尼均使HR、2：1B缩短,而SACT、SNRT、CSNRT、QTC、P-R间期、QRS间期时程明显延长(P＜O．01)。结论大剂量瑞芬太尼对窦房结自律性及房室传导功能有抑制作用。     

The effects of propofol on normal and hypercholesterolemic isolated rabbit heart.

The aim of the present study was to compare the effects of propofol on cardiac contractile force in normal and hypercholesterolemic isolated rabbit hearts. While one group was fed with standard chow pellets (150 g/day), the other group received cholesterol (1% w/w) in addition to the same amount of rabbit chow pellets during 1 month. Hearts from standard-fed rabbits were given intralipid solvent or 25, 50 and 100 microM propofol by infusion. Hypercholesterolemic rabbit hearts were administered 25, 50 and 100 microM propofol by infusion. All concentrations of propofol did not result in any significant change of the heart rates (HR) in two groups. Propofol (25, 50 and 100 microM) infusion induced a concentration- and time-dependent inhibition in left ventricular pressure (LVP) in standard chow diet group (P<.05,.05 and.05, respectively). In hypercholesterolemic rabbit hearts, 25 and 50 microM propofol infusion developed a significant inhibition in LVP when compared with the standard chow diet group (P<.05 and.05, respectively). Propofol (100 microM) infusion developed a significant increase in LVP after 20 min in hypercholesterolemic rabbit hearts when compared with normal rabbit hearts (P<.05). Supratherapeutic concentration of propofol might have cardioprotective effect on hypercholesterolemic rabbit hearts.     

The non-catecholamine-mediated electrophysiological effects of intravenous bethanidine sulfate on the immature mammalian heart

In a preliminary study, we found that bethanidine sulfate had important electrophysiologic effects on the neonatal canine heart, specifically that bethanidine increased atrial effective and functional refractory periods. Other effects (increase in heart rate blood pressure and enhanced atrioventricular conduction) were thought to be due to a release of endogenous catecholamines. To investigate the non-catecholamine-mediated effects of bethanidine, we administered 10 mg/kg i.v. bethanidine to eight neonatal puppies ages 6-14 days pretreated with 0.6 mg/kg of propranolol and compared them with a control group of six neonates that received propranolol followed by a placebo. In the bethanidine group, the mean atrial effective and functional refractory periods increased significantly from 58 to 109 ms and from 108 to 185 ms, respectively (p less than 0.0001). Bethanidine also caused a decrease in resting heart rate (from 154 beats/min postpropranolol to 144 beats/min postbethanidine, p less than 0.002). These effects were not observed in the placebo group. Wenckebach periodicity during incremental atrial pacing did not change significantly. There was a modest increase in the ventricular refractory periods following bethanidine. Thus, the direct electrophysiologic effects of bethanidine in the neonate include a significant prolongation of atrial refractoriness and a decrease in sinus node automaticity. Ventricular refractory periods, while increased, did not show the dramatic prolongation exhibited by the atrium. The atrial specificity of bethanidine is unique and may prove useful in the treatment of supraventricular arrhythmias in the neonatal period.     

The effects of intravenous anaesthetics on the cardiovascular system of the rabbit.

1 A pithed rabbit preparation is described that allows selective stimulation of the vertebral outflows. 2 The responses to stimulation of sympathetic vasopressor fibres were blocked by hexamethonium and phentolamine but potentiated by cocaine, whereas the responses to stimulation of cardioaccelerator fibres were blocked by propranolol. 3 Ketamine, althesin and pentobarbitone enhanced the effects of noradrenaline and attenuated the effects of sympathetic nerve stimulation. Thiopentone enhanced the effects of both noradrenaline and sympathetic nerve stimulation. 4 In pithed rabbits a transient, dose-related cardiovascular depression was produced by each agent irrespective of whether vasomotor tone was present whereas in decerebrate rabbits the corresponding cardiovascular depression was longer lasting. 5 It is concluded that the cardiovascular depression produced by intravenous anaesthetics in intact rabbits is due to a combination of central and peripheral effects.     

The cardiac electrophysiological effects of nifedipine.

A study was carried out on the electrophysiological effects of a sublingually administered antianginal drug: nifedipine (20 mg). The results show a significant shortening of sinus cycle length from 925 +/- 249 msec to 810 +/- 245 msec, (p less than 0.005) and the disappearance of some interpolation and echo zones. There are no significant effects on the other evaluated parameters of sino-atrial and AV-node function. In one case, during atrial pacing, a second-degree, Wenckebach type, A-V block was present only before nifedipine. The following conclusions were reached: 1. nifedipine has no significant electrophysiological effect on the human heart; 2. the electrophysiological effects observed are probably indirect and related to the vasodilating effect of the drug; 3. the absence of direct cardiac electrophysiological actions may be useful in patients suffering from coronary artery disease and presenting disturbances in the formation and/or conduction of the cardiac impulse.     

Antifibrillatory effects of clofilium in the rabbit isolated heart.

1. This study was designed to determine whether clofilium exhibits antifibrillatory activity in a pinacidil + hypoxia-induced model of ventricular fibrillation (VF) in Langendorff-perfused hearts. 2. Ten minutes after exposure to vehicle or clofilium (0.1, 1.0 and 10.0 microM), hearts were exposed to pinacidil (1.25 microM), then subjected to 12 min of hypoxia and reoxygenated. Onset to VF was recorded. Additional groups of hearts were pretreated with UK-68,798 (1.0, 3.0 and 10.0 microM), a delayed rectifier channel blocker, and 5-hydroxydecanoate (10 microM), a known ATP-dependent K+ channel blocker, and subjected to an identical protocol. 3. Clofilium decreased the incidence of VF in a concentration-dependent manner; 7/9 control hearts developed VF vs 1/9 hearts (P = 0.007, Fisher's Exact) treated with 10.0 microM clofilium. In addition, 5-hydroxydecanoate protected hearts from VF, while UK-68,798 pretreatment did not. 4. In a separate group of hearts, electrically-induced VF was converted to sinus rhythm in 10/11 hearts after clofilium was introduced as a bolus. 5. Clofilium is capable of preventing VF in the rabbit isolated heart in a concentration-dependent manner. We have data to suggest that the ability of clofilium to attenuate the effects of pinacidil+hypoxia in our model may include blockade of metabolically active K+ channels, i.e., KATP (glibenclamide-sensitive) channel.     

Effect of ildamen on the heart conduction system in ischemic heart disease patients

Thirty-four patients with ischemic heart disease (IHD) were studied: 18 IHD patients with latent forms of disturbances of conductivity in the atrioventricular junction and sinus node sickness syndrome revealed at frequency stimulation of the heart; 16 patients with acute myocardial infarction complicated with the atrioventricular junction blockade of II and III degrees. Ildamen solution (4 mg) was slowly intravenously infused to all patients under study. Exerting the beta-stimulating effect, ildamen positively influences restoration of the disordered function of the pacemaker and conduction system of the heart: through immediate action on these systems and an increase of the coronary blood flow contributing to improvement of nutrition of the condition system of the heart.     

Cellular electrophysiological effects of the class III antiarrhythmic agents sematilide and clofilium on rabbit atrial tissues.

Sematilide (N-[2-(diethylamino)ethyl]-4- [(methylsulfonyl)amino]benzamide HCl) is a new class III antiarrhythmic agent that has been shown to be effective in preventing reentrant ventricular arrhythmias in experimental animals and humans. In this study, we examined the in vitro effects of sematilide (1-100 microM) on isolated sinoatrial (SA) node, atrioventricular (AV) node, and atrial muscle. These results were then compared to another class III agent, clofilium (1-30 microM). In SA nodal tissue, sematilide increased the action potential duration (APD) and spontaneous cycle length (SCL) in a concentration-dependent manner (EC20% = 15 +/- 3 and 54 +/- 13 microM, respectively). In addition, there was a slight reduction in maximum diastolic potential at 100 microM. Clofilium had similar class III effects, but was approximately 3 to 18 times more potent (EC20% = 6 +/- 2 and 3 +/- 1 microM for the APD and SCL, respectively). Neither agent had a significant effect on the slope of phase 4 nor on other action potential parameters. Results in AV nodal preparations were similar. Both sematilide and clofilium increased the APD and SCL in a concentration-dependent manner, with clofilium being approximately four to six times more potent than sematilide (EC20% for the APD and SCL for sematilide = 12 +/- 4 and 12 +/- 8 microM, respectively, and for clofilium = 2 +/- 1 and 3 +/- 2 microM, respectively). No significant effects were observed on other action potential parameters. Sematilide and clofilium increased the APD and effective refractory period (ERP) in atrial trabeculae in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)     

丙泊酚及咪唑安定对心内传导系统的影响

目的比较丙泊酚及咪唑安定对人体心内传导系统的影响。方法病人20例,随机均分为两组:A组,丙泊酚2 mg/kg诱导,4 mg.kg-1.h-1持续泵注;B组,咪唑安定0.15 mg/kg,1 min内注入。分别在麻醉前、后测定HR、窦房传导时间(SACT)、最大窦房结恢复时间(SNRTMAX)、矫正窦房结恢复时间(CSNRT)、窦房结恢复时间指数(SNRTI)、文氏型A-V传导频率(WB)、P-R间期、QRS波。结果两组患者均使SACT明显延长(P<0.01和P<0.05),A组,WB明显提前(P<0.05),其他参数无明显改变。结论丙泊酚和咪唑安定对窦房结传导均有抑制作用,丙泊酚2 mg/kg静注后还能抑制房室交界区传导。有窦房传导阻滞疾患的病人,丙泊酚和咪唑安定均应谨慎使用。     

甲基莲心碱对兔心内传导系统的影响

在麻醉兔观察了甲基莲心碱(Nef)对心内传导功能的影响。Nef 4 mg/kg iv明显延长兔SACT和CSNRT,增大SNRTI,表明对窦房结传导功能有显著抑制作用。Nef恒速iv 1～8 mg/kg,剂量依赖性地延长兔HBE A—H和H—V,增宽V波,使ECGP—R延长,这些作用与奎尼丁相似。结果表明Nef对心脏房—室、希氏束—浦肯野纤维—心室肌的传导有显著的抑制作用。     

Electrophysiological effects of diclofurime on rabbit and frog atrial heart muscle.

The effects of diclofurime on the electrical activity of the rabbit sinus node, rabbit atria and frog atrial fibres were studied using microelectrode and the double sucrose gap voltage-clamp techniques respectively. In rabbit sinus node, diclofurime (10(-7) M to 10(-6) M) decreased the action potential (AP) amplitude and maximum rate of depolarization (Vmax), increased the AP duration and slowed the sinus rate. In rabbit atria, the drug reduced the amplitude of the depolarizing phase and Vmax, lengthened the AP duration and decreased the resting membrane potential. In frog atrial fibres, the drug (10(-5) M) depolarized the resting membrane potential, decreased Vmax as well as the plateau amplitude. It inhibited the sodium current (INa) with a dissociation constant of 3.7 X 10(-6) M and a one to one relationship between the drug molecule and the Na channel. Diclofurime did not alter the apparent reversal potential for the fast Na current (ENa) but it inhibited the sodium conductance (GNa) in a frequency-dependent manner. Diclofurime also blocked the slow inward current (Islow) without alteration of Eslow. The block of Islow occurred with a dissociation constant of 2 X 10(-5) M and unity stoichiometry. The data suggest that diclofurime might be effective in the control of cardiac arrythmias since it exhibited both local anaesthetic-like and calcium antagonistic properties.     

The anti-arrhythmia activity and effect on the heart conduction system of the new anti-arrhythmia preparation bonnecor

In 10 patients with frequent ventricular extrasystoles there were studied the antiarrhythmic effectiveness and side effects of a new drug bonnecor at a single intravenous administration in doses from 15 to 60 mg (0.17-0.91 mg/kg). It was found that the drug exerted the antiarrhythmic effect at dosages of over 0.4 mg/kg and side effects and toxic effects occurred at dosages of over 0.7 mg/kg. The optimal dose for a single intravenous administration was regarded to be the dose of 0.6 mg/kg. The mechanisms of action of bonnecor were studied during intracardiac electrophysiological investigation. The drug was shown to suppress the conduction of excitation along the atrioventricular node, the His-Purkinje system, the ventricular myocardium and the abnormal pathways of conduction. Thus, bonnecor may be referred to as an agent of class I according to the classification of Vaughan Williams. When administered intravenously (0.6 mg/kg) bonnecor was found to interrupt and prevent the recurrent development of atrioventricular tachycardia and also supraventricular tachycardias at the presence of the abnormal pathways of conduction.     

Electrophysiological effects of melperone on isolated rabbit heart muscles

1. Electrophysiological effects of melperone on isolated atrial and ventricular muscle preparations of the rabbit were studied by a conventional microelectrode technique. 2. Melperone (3.3 microM) prolonged the action potential duration and effective refractory period of the atrial preparations without affecting the maximum rate of depolarization (Vmax). These effects of melperone on action potential duration and effective refractory period were inhibited by a low potassium perfusate (2.7 mM). 3. A high concentration of melperone (16.6 microM) decreased Vmax of atrial preparations. In ventricular muscles, melperone at either concentration decreased Vmax, although the increase in action potential duration was greater than in the atrium. 4. Depression of Vmax of ventricular muscles by melperone was found to be augmented by an increase of stimulation frequency and drug concentration. 5. The rate of onset of rate-dependent block of Vmax in ventricle was increased with drug concentration and frequency of stimulation. However, the time constant of recovery from rate-dependent block was almost constant. The kinetics of rate-dependent block of Vmax by melperone were approximately similar to those of quinidine and disopyramide. Consequently it is concluded that melperone possesses class 1a antiarrhythmic activity as well as class 3 activity.     

Comparisons of the electrophysiological effects of intravenous sotalol and propranolol on the immature mammalian heart

Sotalol is a beta blocker that has also been reported to exert class III antiarrhythmic effects. To evaluate the effects of sotalol on the immature heart, and specifically to assess the relative importance of its class III action, the electrophysiologic effects of incremental doses of intravenous dl-sotalol (cumulative dose of 8 mg/kg) were studied in 11 intact canines (ages 4-15 days) utilizing intracardiac programmed stimulation and electrogram recording techniques. These results were compared to the electrophysiologic effects obtained in an additional 14 neonatal canines given 0.6 mg/kg of the beta blocker propranolol intravenously. Sotalol caused a greater increase than propranolol in the resting sinus cycle length (45 vs. 4%). Importantly, sotalol resulted in greater increases in atrial and ventricular muscle refractoriness than did propranolol (AERP--77 vs. 4%, AFRP--57 vs. 6%; VERP--53 vs. 4%, VFRP--51 vs. 7%). Thus, the electrophysiologic effects of sotalol include large changes in myocardial refractoriness that are not observed with simple beta blockade induced by propranolol. These results suggest that sotalol exerts a significant class III effect in the immature mammalian heart, and thus may be useful as an antiarrhythmic agent in the neonate.     

Acute energetic effects of daunomycin on rabbit heart muscle

The acute effects of daunomycin on the mechanical and energetic outputs of rabbit papillary muscles have been examined at 27 degrees C using a myothermic technique. Contrary to expectations, daunomycin, in concentrations ranging from 10 to 160 micrograms/ml, acted as a positive inotropic agent in terms of peak stress development and work output. The rate of stress development was, however, slightly depressed, and the major mechanical effect of the drug was to prolong the relaxation phase so that there were large drug-dependent increments in the stress-time integral. Daunomycin at a concentration of 80 micrograms/ml produced a 22% increment in peak stress development and a 74% increment in stress-time integral. The linear relationship between total (active + passive) stress and heat production was altered such that there was a 73% increment in the activation heat component (intercept) and a 37% increase in the energy cost per unit stress development (slope). In afterloaded isotonic contractions, daunomycin increased the mean work output (W; averaged over all load levels) by 49%, but there was an even greater increment in the associated energy expenditure, ET, which rose by 66%. Consequently, the overall mechanical efficiency (W/ET X 100%) fell slightly. It is concluded that, in the rabbit, daunomycin in the acute situation increases total calcium delivery to the myofilaments and decreases the "apparent" transduction efficiency. These acute effects are the opposite of those reported in papillary muscles taken from rabbits in cardiac failure induced by chronic daunomycin administration. The short-term effects of daunomycin in the rabbit differ substantially from those seen in the rat and guinea pig.     

Electrophysiological effects of amiodarone on isolated rabbit heart muscles

We studied the electrophysiological effects of amiodarone on isolated rabbit heart muscles by conventional microelectrode techniques. It significantly suppressed not only sinus node functions (basic cycle length, sinus recovery time, and corrected sinus recovery time) but also atrioventricular node functions (AH interval, effective refractory period, and functional refractory period) by both superfusion (10 micrograms/ml amiodarone in Tyrode solution) and long-term oral administration (50 mg/day for 2 weeks, then 25 mg/day for 4-6 weeks). On the other hand, oral administration significantly lengthened the action potential duration and effective refractory period of the left atrium and the right ventricle, while superfusion did not. The maximum rate of depolarization, action potential amplitude, and diastolic resting potential were not changed by either route of administration. It is thought that the action of amiodarone on the sinus node and on the atrioventricular node is mainly due to its noncompetitive sympathetic inhibition, and that its action on the left atrium and on the right ventricle is mainly due to reduction of serum triiodothyronine, which requires long-term administration of amiodarone.     

Electrophysiological effects of cobra cardiotoxin on rabbit heart cells

Effects on transmembrane potentials of cardiotoxin isolated from Formosan cobra venom were studied on rabbit atrial cells by means of electrophysiological techniques. It was found that cardiotoxin at a concentration of 10⁻⁵ g per ml caused a progressive and irreversible decrease of the resting potential in myocardial cells starting 5 min after addition of the toxin. The decrease in maximum diastolic repolarization of the pacemaker type cells occurred much later and to a much less extent. Associated with the decrease of resting potential, the magnitude and rate of rise of the action potential, the overshoot, the time to 80% repolarization and the spike ionic conductance were also decreased. The effect of the toxin on the membrane potential was not altered by either tetrodotoxin or sodium removal but was inhibited by high calcium. It is suggested that disintegration of the membrane structure is responsible for the membrane depolarization.     

The antiarrhythmic and cardiac electrophysiological effects of buprenorphine.

1. The effects of buprenorphine, given intravenously, on the incidence and severity of early acute coronary artery occlusion-induced arrhythmias were examined in anaesthetised rats. The electrophysiological effects of buprenorphine were also examined in sheep Purkinje fibres and rat papillary muscles, superfused in vitro with either a normal or a hypoxic, hyperkalaemic and acidotic physiological salt solution (PSS). 2. In anaesthetised rats subjected to acute coronary artery occlusion, pretreatment with buprenorphine (1 mg kg-1 i.v.) markedly reduced the incidence of ventricular extra-systoles during the initial 30 min post-occlusion period. The incidence of ventricular fibrillation (VF) was also significantly reduced from 56% to 10%. 3. At the antiarrhythmic dose (1 mg kg -1), buprenorphine also attenuated the sudden fall in systemic arterial blood pressure induced by acute coronary artery ligation. 4. In normal sheep Purkinje fibres and rat papillary muscles, buprenorphine (10(-6)-10(-5) M) significantly reduced the action potential height and maximum rate of depolarisation of phase zero (MRD) and prolonged the duration of the action potential. 5. Superfusion of sheep Purkinje fibres and rat papillary muscles with a hypoxic, hyperkalaemic and acidotic PSS resulted in marked reductions in resting membrane potential, upstroke and duration of the action potential. 6. In the presence of the modified compared with normal PSS, buprenorphine reduced the action potential height and MRD of both sheep Purkinje fibres and rat papillary muscles to a greater extent, although its ability to prolong the action potential duration was attenuated. 7. The antiarrhythmic effects of buprenorphine observed in vivo may be explained by its direct cardiac electrophysiological effects.(ABSTRACT TRUNCATED AT 250 WORDS)