Shuji Kikushima

Triggering mechanism for neurally mediated syncope induced by head-up tilt test: Role of catecholamines and response to propranolol

OBJECTIVES We studied the triggering mechanism for neurally mediated syncope. BACKGROUND Although increased transient sympathetic tone is thought to be necessary for the development of neurally mediated syncope, little is known about the triggering mechanism for neurally mediated syncope. METHODS Plasma epinephrine (EP) and norepinephrine (NE) levels were assessed in 20 syncope patients during tilt test (80 degrees, 15 min) with and without isoproterenol (ISP, 0.01, 0.02 microg/kg/min). If syncope occurred, propranolol (0.1 mg/kg) was injected. RESULTS Eight patients experienced syncope during tilting alone, and 9 patients required ISP for syncope. In the negative response without ISP, NE showed a small statistical 1.7-fold increase at end of tilting and EP did not change during tilting. When syncope occurred during tilting alone, a significant 11.7-fold increase in EP at syncope was registered concomitant with a small 2.5-fold increase in NE. When patients experienced syncope during tilting with ISP, a significant 5.0-fold increase in EP at syncope was registered concomitant with a small 1.7-fold increase in NE. In patients without ISP, propranolol did not interrupt syncope. In patients with ISP, six of eight receiving propranolol responded to tilting negatively. CONCLUSIONS An increase of NE levels may result in inhibition of syncope and an EP surge may be a triggering mechanism for neurally mediated syncope. Comparatively low levels of EP may be enough to induce syncope during tilting with ISP compared with tilting alone. Propranolol is not effective in patients without ISP, but it frequently inhibits syncope in patients with ISP. Propranolol (0.1 mg/kg) may be insufficient to block the actions of high levels of circulating EP.

Sustained Left Ventricular Tachycardia Terminated by Dipyridamole: Cyclic AMPMediated Triggered Activity as a Possible Mechanism

Sustained VT in two patients was terminated by intravenous administration of dipyridamole, an adenosine transport inhibitor. VT was induced by rapid atrial or ventricular pacing, isoproterenol, or dibutyryl cyclic AMP infusion, or exercise. VT also was aborted by adenosine triphosphate or acetylcholine injection, or by vagal stimulation. VT was terminated or prevented by verapamil or propranolol. In addition, arrhythmias were prevented by oral administration of dipyridamole. These results suggest that VT is due to cyclic AMP‐mediated triggered activity and that inhibition by dipyridamole may be due to a reduction in the intracellular concentration of cyclic AMP.

Effects of nicorandil, a potassium channel opener, on idiopathic ventricular tachycardia.

OBJECTIVES We assessed the effects of the adenosine triphosphate (ATP)-sensitive potassium channel opener, nicorandil, on ATP- and verapamil-responsive ventricular tachycardias (VTs). BACKGROUND Adenosine- or ATP-sensitive VTs are thought to be due to a nonreentrant mechanism, presumably delayed afterdepolarization. We suggest that this potassium channel opener may suppress ATP- and verapamil-sensitive VTs. METHOD The subjects included 13 patients with idiopathic VTs, 7 of whom had sustained VT and 6 of whom had nonsustained VT. We evaluated the effects of ATP, nicorandil and verapamil on VTs. RESULTS Sustained VT: Verapamil had preventive effects on seven VTs. Four VTs were terminated by ATP, and of these, nicorandil terminated two and prevented exercise-induced VT in the two others. Three ATP-insensitive VTs, which were determined to be due to a reentry by an electrophysiologic study, were not terminated by nicorandil. Nonsustained VT: All six VTs were inhibited by ATP, and five of these were suppressed by nicorandil. Verapamil inhibited four of the five VTs. QT intervals and the corrected QT intervals were significantly shortened by nicorandil. CONCLUSIONS Nicorandil suppresses ATP- and verapamil-responsive VTs. One of the mechanisms of suppression by nicorandil might be related to a reduction of calcium in the myocardium, because it reduces the action potential duration.