Gu Nter Breithardt

Sinus node recovery time and calculated sinoatrial conduction time in normal subjects and patients with sinus node dysfunction.

In 61 patients sinus node function was tested by programmed (sinoatrial conduction time, SACT) and overdrive atrial pacing (sinus node recovery time, SRT). In the control group (N = 20), mean sinus cycle length was 773 ± 140.2 msec, mean absolute SRT 1044 ± 215.8 msec [corrected SRT (CSRT) 270 ± 112.5 msec; mean ± SD] and calculated SACT was 82 19.2 msec. The upper limit of normal SACT was defined as 120 msec. In 41 patients with sinus node dysfunction, mean age (55 ± 14.7 years), mean spontaneous cycle length during the study (1094 ± 248.0 msec), the lowest heart rate observed (42 7.5 beats/min), maximal SRT (2110 ± 1269.1 msec), maximal CSRT (1016 1182.8 msec), and calculated SACT (126 ± 47.3 msec) were significantly longer than in the control group. Abnormalities of sinus node function, as evidenced by the degree of spontaneous bradycardia, SRT and calculated SACT were more frequent in patients with bradycardia-tachycardia syndrome or spontaneous sinoatrial block than in those exhibiting isolated sinus bradycardia. We conclude 1) that in patients with sinus node dysfunction both sinus node automaticity and sinoatrial conduction may be abnormal, and 2) that overdrive and programmed premature atrial stimulation can separate patients with sinus node dysfunction according to their clinical presentation.

Comparison of d,l-Sotalol and Implantable Defibrillators for Treatment of Sustained Ventricular Tachycardia or Fibrillation in Patients With Coronary Artery Disease

BACKGROUND Implantable cardioverter-defibrillators (ICDs) and d,l-sotalol are widely used to treat ventricular tachyarrhythmia and ventricular fibrillation (VT/VF). The purpose of this study was to compare the long-term efficacy of d,l-sotalol and ICDs in patients with coronary artery disease. METHODS AND RESULTS In a case-control study, 50 patients treated with oral d,l-sotalol were matched to 50 patients treated with ICDs. Both groups were matched for sex (82 men), age (58 +/- 10 years), ejection fraction (40 +/- 12%), extent of coronary artery disease, presenting arrhythmia, and year that treatment began. In all patients in the sotalol group, VT/VF was inducible in the drug-free electrophysiological study. Induction of sustained VT/VF was suppressed by d,l-sotalol (438 +/- 95 mg/d). In the ICD group, either VT/VF was not inducible (n = 5) or inducible sustained VT/VF was refractory to antiarrhythmic drug treatment (n = 45). Sotalol treatment led to a marked reduction in arrhythmic events. Whereas 83% of the patients in the sotalol group were free of sudden death and nonfatal VT at 3 years, only 33% of the ICD patients did not receive appropriate ICD therapies (P < .005). Actuarial rates for absence of sudden death at 3 years were 85% in the sotalol group and 100% in the ICD group (P < .005). Actuarial rates for overall survival at 3 years were 75% in the sotalol group and 85% in the ICD group (P = .02). CONCLUSIONS In this case-control study, ICD therapy was more effective tha electrophysiologically guided antiar-rhythmic treatment with d,l-sotalol in prevention of sudden death and reduction of total morality in patients with coronary artery disease. Prospective studies are needed to confirm these results.

The role of the autonomic nervous system in the action of verapamil on the sinus node in man

SummaryTo elucidate the role of the autonomic nervous system in modulating the effect of verapamil on sinus node (SN) function, five volunteers were repeatedly studied both with and without prior autonomic blockade.Verapamil alone (0.1 mg/kg i.v.) caused a significant decrease in spontaneous cycle length (SCL) from 1104±111.6 msec to 891±67 msec (mean ±S.D., P<0.01). After pretreatment with propranolol (0.1 mg/kg i.v.) and atropine (0.02 mg/kg i.v.), verapamil had an opposite effect on SCL with an increase from 686±66 msec (pre) to a plateau alternating between 690 msec and 712 msec (post) (P<0.01). Pretreatment with propranolol alone did not prevent the decrease in SCL after injection of verapamil; SCL changed from 1295±85 msec to 1020±87 msec (P<0.01). The extent of this decrease in SCL was similar to the effect of verapamil without any pretreatment. After atropine pretreatment, there was a small but insignificant decrease in SCL during the first five minutes; whereas later SCL increased.Verapamil led to a fall in blood pressure. After pretreatment with propranolol there was no significant change in blood pressure after injection of verapamil; whereas after pretreatment with either atropine alone or with propranolol and atropine there was a significant decrease in blood pressure.The results suggest that the autonomic nervous system plays an important part in modulating the effect of verapamil on SN function in man. The cardio-accelerating effect of verapamil is either provoked by a fall in blood pressure and a consecutive restraint of vagal innervation on the sinus node or a direct vagolytic action of the drug. An increase in sympathetic tone seems to be less important.ZusammenfassungDie Bedeutung des autonomen vegetativen Nervensystems für die Wirkung von Verapamil auf die Sinusknotenfunktion wurde bei 5 freiwilligen Versuchspersonen wiederholt mit und ohne autonome Blockade untersucht.Verapamil (0,1 mg/kg i.v.) bewirkte eine Abnahme der spontanen Zykluslänge von 1104±111,6 ms auf 891±67 ms (X±sx; P<0,01). Nach Vorbehandlung mit Propranolol (0,1 mg/kg i.v.) und Atropin (0,02 mg/kg i.v.) hatte Verapamil einen gegenteiligen Effekt in Form einer Zunahme der Zykluslänge von 686±66 ms auf Werte zwischen 690 ms bis 712 ms (P<0,01). Nach alleiniger Vorbehandlung mit Propranolol führte Verapamil zu einer Abnahme der spontanen Zykluslänge von 1295±85 ms auf 1020±87 ms (P<0,01). Das Ausmaß dieser Abnahme ähnelte der Wirkung von Verapamil ohne Vorbehandlung. Nach alleiniger Vorbehandlung mit Atropin wurde lediglich eine geringe, jedoch nicht signifikante Abnahme der spontanen Zykluslänge während der ersten fünf Minuten beobachtet, während sie später zunahm.Der Blutdruck fiel nach Verapamil ab. Nach Vorbehandlung mit Propranolol änderte sich der Blutdruck nach Verapamil nicht signifikant, während Vorbehandlung entweder mit Atropin allein oder mit Propranolol plus Atropin zu einer signifikanten Abnahme des Blutdruckes führten.Die Befunde lassen erkennen, daß das autonome Nervensystem eine wichtige Rolle bei der Wirkung von Verapamil auf die Sinusknotenfunktion ausübt. Die frequenzsteigernde Wirkung von Verapamil wird entweder durch den Blutdruckabfall und eine nachfolgende Abnahme des Vagotonus verursacht oder Verapamil hat eine direkte vagolytische Wirkung. Eine Zunahme des Sympathikotonus dürfte von untergeordneter Bedeutung für diesen frequenzsteigernden Effekt sein, da er sich durch Betarezeptorenblockade nicht verhindern ließ.