Acute effects of amiodarone upon the canine sinus node and atrioventricular junctional region

Amiodarone was selectively perfused into the sinus node artery and atrioventricular node artery of 51 dogs. Amiodarone had an immediate negative chronotropic and dromotropic effect. Threshold concentration was 2.5 micrograms/ml. 25 and 50 micrograms/ml of amiodarone injected into the sinus node artery slowed the heart by 25.6 +/- 3.1 and 33.7 +/- 2.6 beats/min (mean +/- 1 SEM), respectively. Amiodarone 25 and 50 micrograms/ml injected into the AV node artery during AV junctional rhythm slowed the AV junctional pacemaker by 12.2 +/- 1.8 and 17.4 +/- 1.7 beats/min, respectively. Injections of amiodarone into the AV node artery during sinus rhythm regularly increased AV conduction time sometimes causing 2 degrees AV block at the highest concentration used. Impaired conduction was exclusively measured at the level of the A-H interval in the His electrogram. Neither atropine nor propranolol prevented the negative chronotropic effects of amiodarone. Amiodarone had no significant effect on sinus node response to either stellate stimulation or intranodal administration of norepinephrine. The negative chronotropic action of amiodarone was significantly enhanced when amiodarone was administered in a perfusate containing low (0.6 mM) instead of normal calcium. Taken collectively these observations indicate that amiodarone has immediate depressant electrophysiologic effects on both the sinus node and the AV junction and that these early effects might involve the blockade of the slow channel.     

Adenosine mediates the negative chronotropic action of adenosine 5'-triphosphate in the canine sinus node

ATP exerts pronounced electrophysiologic effects in the mammalian heart. The present study tested the hypothesis that the negative chronotropic action of ATP in the canine sinus node is dependent on its degradation to adenosine. Increasing doses of the following compounds were administered in the sinus nodal artery of 12 open chest dogs (either sex, 30-35 kg) anesthetized with pentobarbital (30 mg/kg i.v.): adenosine, ATP, alpha,beta methylene-ATP (AMPCPP) and beta,gamma methylene-ATP (AMPPCP). Right atrial, His bundle and right ventricular electrograms as well as Lead II ECG and systemic arterial blood pressure were monitored continuously and recorded. The depressant effects of test compounds on the sinus node were assessed from the prolongation of sinus cycle length and the duration of junctional escape rhythm which they induced. Data were used to plot dose-response curves for the four test compounds. The order of potency was adenosine greater than or equal to ATP greater than or equal to AMPPCP much greater than AMPCPP = 0. In 3 of 12 dogs the emergence of junctional escape rhythm was observed after the highest dose of either adenosine, ATP or AMPPCP. In addition, aminophylline, a selective competitive inhibitor of adenosine at P1-purinoceptor site, reduced the effects of maximal doses of adenosine, ATP and AMPPCP by 52 +/- 7, 67 +/- 8 and 72 +/- 6%, respectively (each, P less than .05; AMPPCP vs. adenosine, P less than .05). The present data indicate that the negative chronotropic action of ATP is due to its rapid catabolism to adenosine and the action of adenosine at P1-purinoceptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

The electrophysiological effects of ouabain on sinus node and atrium in man.

Electrophysiological studies were performed in 16 patients before and 30 min after intravenous administration of ouabain (0.1 mg/kg). P-A interval (mean+/-SEM) was 40+/-2.1 ms before and 44+/- 1.5 ms after ouabain (P less than 0.001). Atrial effective and functional refractory periods (ERP and FRP) were measured in all patients during sinus rhythm and during driving at equivalent paced rates in 12 patients. The mean atrial ERP and FRP during sinus rhythm were, respectively, 244+/-10.5 and 307+/-11.0 ms before and 253+/-9.7 and 318+/-11.4 ms after infusion of ouabain (NS). Mean atrial ERP and FRP during driving were, respectively, 231+/-15.3 and 264+/-14.9 ms before and 266+/-18.6 and 296+/-19.7 ms after ouabain (P less than 0.01 and P less than 0.01). Mean sinus cycle length and sinus recovery times were, respectively, 887+/-31.2 and 1,113+/-38.7 ms before and 905+/-38.2 and 1,008+/-30.7 ms after infusion of ouabain (NS and P less than 0.005). Calculated sinoatrial conduction times before and after ouabain were 90+/-6.8 and 110+/-8.5 ms, respectively (P less than 0.005). In summary, ouabain produced depression of intraatrial conduction as manifested by increase in P-A interval and atrial effective and functional refractory periods. Ouabain significantly increased calculated sinoatrial conduction time without significant effect on spontaneous sinus cycle length.     

Determination of the sinus node recovery time

The interrelationship between the sinus node recovery time and the rate of atrial stimulation was investigated in clinical experiments. The sinus node recovery time measured with the aid of atrial stimulation according to the recovery of atrial activity after stimulation was completed did not mirror the genuine sinus node recovery time. An empiric formula is suggested, permitting the determination of the genuine sinus node recovery time on the basis of the initial rhythm rate and maximal value of the sinus node recovery time measured according to the atrial activity recovery.     

消旋去甲乌药碱对窦房结功能电生理的影响

目的:探讨消旋去甲乌药碱治疗病态窦房结综合征的作用机制.方法:40只杂种家兔随机分为窦房结功能正常组和窦房结功能受损(SND)组,每组随机分为用药组和对照组(n=10).采用甲醛溶液湿敷窦房结的方法制备SND模型.用药组5 min内经耳缘静脉注入消旋去甲乌药碱0.04 mg/kg,20 min后测定用药前、后窦房结功能电生理指标--窦房结恢复时间(SNRT)、纠正窦房结恢复时间(CSNRT)、总窦房传导时间(TSACT)和窦性心律周期(SCL)的变化;正常组用生理盐水10 ml作对照用药.结果:①窦房结功能正常组和SND组在给予消旋去甲乌药碱后,SNRT、CSNRT、TSACT和SCL均较对照组明显缩短(P<0.05或P<0.01).②消旋去甲乌药碱对SND组窦房结功能电生理影响明显大于窦房结功能正常组(P均<0.01);对窦房结功能受损引起的心律失常治疗作用有统计学意义(P<0.05).结论:窦房结自律性的提高及窦房、房室传导功能改善是消旋去甲乌药碱治疗病态窦房结综合征主要的电生理机制.     

Antihypertensive effects of clonidine.

The antihypertensive effect of clonidine given either two or three times a day with a diuretic was compared in a double-blind crossover study in 18 hypertensive patients. In 11 patients given clonidine three times a day there was better control of blood pressure, although the differences in most instances were of the order of only a few millimeters Hg. There were no differences in the frequency or severity of side effects. Clonidine twice daily with a diuretic appears to be adequate for most patients.     

Popeye proteins: muscle for the aging sinus node

The electrical impulses that dictate the rhythm of the heartbeat in normal situations and during exercise or stress are initiated by a small number of sinus node pacemaker cells. Senescence and dysfunction of the sinus node affects many people later in life, causing physiologically inappropriate heart rates, but the underlying mechanisms are not well understood. In this issue of the JCI, Froese and colleagues show that deficiency in either Popeye domain containing 1 (Popdc1) or Popdc2 leads to sinus node dysfunction under stressed conditions in aged mice. The mechanism reported to underlie the effects of Popdc1/2 deficiency in mice may cause the stress-induced sinus node dysfunction found in many aged individuals and may point to new strategies for therapeutic intervention.     

Sick sinus syndrome and AV node re-entry.

A 69-year-old man presented with recurrent palpitations since childhood. Electrophysiology studies performed on two separate occasions revealed the combination of sick sinus syndrome and AV node re-entrant tachycardia. The case is reported because it illustrates marked temporal variability in the electrophysiological properties of the dual AV node pathways, and also deleterious effects of verapamil on sinoatrial node function.     

Dual effects of clonidine on micturition reflex in urethane anesthetized rats

The effects of clonidine (CLO) on reflexly activated bladder motility have been examined in urethane-anesthetized rats and compared to its effects on field stimulation-induced contractions of isolated urinary bladder. Intravenous CLO suppressed micturition reflex transiently in a yohimbine-sensitive manner. The suppressive effect of i.v. CLO was greater after surgical sympathectomy (bilateral section of the hypogastric nerves). Intracisternal CLO was more effective than topical (on the bladder dome) or intracerebroventricular CLO in suppressing micturition. When tested in experimental conditions involving activation of both excitatory and inhibitory reflexes to the bladder CLO produced either inhibitory and/or excitatory effects on bladder motility in dependence of factors such as dose, route of administration and integrity of the sympathetic (inhibitory) innervation to the bladder. CLO suppressed bladder contractions produced by dimethylphenilpiperazinium, a ganglionic stimulant, and reduced those produced by postganglionic nerve stimulation. CLO inhibited, in a yohimbine-sensitive manner, amplitude of field stimulation-induced contractions of isolated rat bladder, and its effectiveness was inversely related to the frequency of stimulation. Our findings are suggestive that the inhibitory action of CLO on micturition reflex is counteracted, in normal animals, by a negative feedback on sympathetic inhibitory influences carried out through the hypogastric nerves.     

Psychosomatic ratios and their correction in the autonomic dysfunction of the sinus node

The study was undertaken to examine the ratio of mental to somatic disorders in patients with autonomic sinus nodal dysfunction (ASND) and the capacities of correction of revealed disorders with the atypical benzodiazepine drug clonazepam. Thirty-two patients with ASND were examined. The diagnosis of ASND was verified by 24-hour ECG monitoring and transesophageal atrial pacing, by performing autonomic cardiac block with atropine and obsidan. In addition to physical examination, heart rhythm variability was studied during relaxed and intensive wake; psychological studies using the conventional tests were conducted, and autonomic disorders were explored by means of original scored somatic, hyperventilation) questionnaires. After examination, the patients received a 1.5-to-2-month course of therapy with clonazepam in a daily dose of 1.5-2 mg. The study has revealed that clinical symptomatology in ASND is greatly determined by psychosomatic disorders. ASND was marked by anxious depressions in combination with inadequate peripheral (to a greater extent, sympathetic) neurovegetative exposures with the simultaneous activation of cerebral ergotropic effects. The use of clonazepam in ASND greatly improved its clinical picture, by eliminating, in the overwhelming majority of cases, clinical symptoms, including rhythm and conduction disturbances that are characteristic of ASND.