Amiodarone inhibits cardiac ATP-sensitive potassium channels.

INTRODUCTION: ATP-sensitive K+ channels (K(ATP)) are expressed abundantly in cardiovascular tissues. Blocking this channel in experimental models of ischemia can reduce arrhythmias. We investigated the acute effects of amiodarone on the activity of cardiac sarcolemmal K(ATP) channels and their sensitivity to ATP. METHODS AND RESULTS: Single K(ATP) channel activity was recorded using inside-out patches from rat ventricular myocytes (symmetric 140 mM K+ solutions and a pipette potential of +40 mV). Amiodarone inhibited K(ATP) channel activity in a concentration-dependent manner. After 60 seconds of exposure to amiodarone, the fraction of mean patch current relative to baseline current was 1.0 +/- 0.05 (n = 4), 0.8 +/- 0.07 (n = 4), 0.6 +/- 0.07 (n = 5), and 0.2 +/- 0.05 (n = 7) with 0, 0.1, 1.0, or 10 microM amiodarone, respectively (IC50 = 2.3 microM). ATP sensitivity was greater in the presence of amiodarone (EC50 = 13 +/- 0.2 microM in the presence of 10 microM amiodarone vs 43 +/- 0.1 microM in controls, n = 5; P < 0.05). Kinetic analysis showed that open and short closed intervals (bursting activity) were unchanged by 1 microM amiodarone, whereas interburst closed intervals were prolonged. Amiodarone also inhibited whole cell K(ATP) channel current (activated by 100 microM bimakalim). After a 10-minute application of amiodarone (10 microM), relative current was 0.71 +/- 0.03 vs 0.92 +/- 0.09 in control (P < 0.03). CONCLUSION: Amiodarone rapidly inhibited K(ATP) channel activity by both promoting channel closure and increasing ATP sensitivity. These actions may contribute to the antiarrhythmic properties of amiodarone.

Atrial arrhythmia following a biatrial approach to mitral valve surgery.

The biatrial approach to exposing the mitral valve during surgery has the potential for improving visualization of the valve with minimal cardiac manipulation. This procedure, involving a right atriotomy and an extended transseptal incision, may isolate the sinus node from its normal blood supply and autonomic innervation. Thirty-eight consecutive patients undergoing this procedure were examined. Twenty-two of these patients (58%) were admitted in normal sinus rhythm and 15 (40%) were in atrial fibrillation (AF) or atrial flutter. Of the 22 patients admitted in normal sinus rhythm, only 3 patients remained in this rhythm at discharge. Fourteen of the 22 patients were discharged in a slow, low atrial rhythm. All of the patients admitted in AF were discharged in AF. Of the 14 patients discharged in a low atrial rhythm, the rhythm persisted in eleven patients (80%) at a mean of 6-month follow-up. The routine use of this transseptal approach to mitral valve surgery needs further assessment in light of the predictable loss of the sinus mechanism.

Mapping reentry around atriotomy scars using double potentials.

Supraventricular arrhythmias, often seen in patients after cardiac surgery, may be associated with scars produced in the atria at the time of surgery. Double potentials, found in the presence of functional or anatomical block, can define the limits and critical regions of a reentrant circuit associated with the atriotomy scars. We describe six patients with seven distinct atrial tachycardias in whom atriotomy scars were successfully mapped during intraatrial reentry utilizing the presence and interelectrogram relationship of observed double potentials. The reentrant circuit was mapped in all patients by following the relationship between double potentials along the surgical scar, assuming that they would be widely split in the middle of the scar and merge into a single continuous fractionated potential at the apex of the scar. At this site, atrial pacing was performed to entrain the tachycardia and confirm the participation of the atriotomy scar in the clinically relevant atrial tachycardia. Radiofrequency ablation was performed from the site of electrogram fusion to the nearest anatomical obstacle. Five of seven atrial tachycardias were successfully ablated utilizing this technique over a mean follow-up of 10 months. We proposed that these double potentials and their interelectrogram relationship are an effective means of mapping atriotomy scars and guiding successful radiofrequency ablation.

Protruding atheromas of the aortic arch in symptomatic patients with carotid artery disease.

Protruding aortic arch atheromas are associated with otherwise unexplained strokes and transient ischemic attacks. Therefore aortic atheromas also may be important in patients with carotid artery disease. Forty-five patients with > or = 50% carotid stenosis and stroke or transient ischemic attack within 6 weeks underwent transesophageal echocardiographic examination (TEE). They were matched for age, sex, and hypertension with 45 control subjects who had also had a recent cerebral event but in whom significant carotid stenosis was absent. Protruding aortic arch atheromas were present in 17 (38%) of 45 patients with carotid disease and only 7 (16%) of 45 of control subjects (p = 0.02). Mobile atheromas (with the greatest embolic potential) were present almost exclusively in case patients, 6 (13%) of 45, versus 1 (2%) of 45 control subjects (p = 0.05). Case patients with mobile atheromas had the most severe carotid stenosis ( > or = 80%). Cerebral symptoms were discordant with the side of the carotid stenosis in 10 case patients, and 4 had atheromas. In conclusion, protruding atheromas of the aortic arch are present in significant numbers of symptomatic patients with carotid artery disease. These atheromas may represent an additional cause of symptoms in patients with carotid stenosis. TEE to look for protruding aortic atheromas may be considered in patients with neurologic events despite the presence of significant carotid stenosis, especially if the symptoms are discordant with the side of carotid stenosis.

Correlates of spontaneous echo contrast in patients with mitral stenosis and normal sinus rhythm.

The purpose of this study was to evaluate the correlates of spontaneous echo contrast in mitral stenosis and normal sinus rhythm. Spontaneous echo contrast is associated with clot formation and embolic phenomena. It has been noted in conditions involving blood stasis, especially mitral stenosis and atrial fibrillation, but the correlates of spontaneous echo contrast in patients with mitral stenosis and normal sinus rhythm have not been extensively evaluated. The transthoracic and transesophageal echocardiograms and clinical findings of 47 patients with mitral stenosis and normal sinus rhythm were reviewed. Left atrial size, mean transmitral gradient, and valve area were measured, and the presence or absence of spontaneous echo contrast in the left atrium was noted. Spontaneous echo contrast was found in the echocardiograms of 21 (45%, group 1) of 47 patients. There was no contrast in those of the other 26 patients (group 2). Mean transmitral gradient was significantly higher in group 1 (13.6 +/- 5.2 mm Hg) than in group 2 (10.5 +/- 4.9 mm Hg) (p < 0.05). Mitral valve area was significantly smaller in group 1 than in group 2 (1.0 +/- 0.5 vs 1.4 +/- 0.5 cm2; p < 0.02). There was a trend toward a higher prevalence of significant mitral regurgitation in group 2. There was no significant difference with respect to age, left atrial size, history of embolism, or warfarin therapy. We conclude that spontaneous echo contrast in the left atrium of patients with mitral stenosis and normal sinus rhythm is common and is associated with a significantly smaller mitral valve area and higher mitral gradient.(ABSTRACT TRUNCATED AT 250 WORDS)