Case report: SARS-CoV-2 specific T-cells are associated with myocarditis after COVID-19 vaccination with mRNA-1273.

Vaccination of SARS-CoV-2 with BNT162b2 or mRNA-1273 both have a low incidence of induction of myocarditis. Here we report on utilizing adaptive immune receptor repertoire sequencing (AIRR-Seq) as a way to assess the specificity of tissue infiltrating immune cells.

A Retrograde Transaortic/Transmitral Approach for Radiofrequency Ablation of Adenosine-Sensitive Atrial Tachycardia Arising Near the Apex of Koch's Triangle: A Case Study Approach and Review of the Literature.

Atrial tachycardias (ATs) are relatively uncommon and their mechanisms include reentry or may be focal. The characteristics and radiofrequency (RF) ablation of adenosine-sensitive AT arising near the apex of Koch's triangle have been reported. We report a case of successful RF ablation of this tachycardia by using a retrograde transaortic/transmitral approach. An electrophysiological study performed during sinus rhythm showed continuous anterograde atrioventricular nodal and no ventriculoatrial conduction. The tachycardia could be induced and terminated by atrial extrastimulation and rapid atrial pacing. Although inverse resetting response pattern was observed, tachycardia termination by intravenous low-dose adenosine was rather suggestive of triggered activity as the mechanism. The earliest atrial activation was recorded in the His-bundle region. After ineffective right-sided attempts and failure to find earlier atrial activity during mapping the noncoronary sinus of Valsalva, this tachycardia was successfully ablated from the left atrial septum by using a retrograde transaortic/transmitral approach. This report demonstrates the feasibility of a novel retrograde left atrial approach for RF ablation of adenosine-sensitive AT originating from the apex of Koch's triangle.

Adenosine-sensitive decremental conduction over short non-decremental atrioventricular accessory pathways after radiofrequency ablation: case series.

INTRODUCTION: Decremental conduction in short anterograde atrioventricular accessory pathways (AV-APs) is rare. CASE PRESENTATION: We report on two cases with radiofrequency (RF) ablation of anterograde fast non-decremental AV-AP conduction. In Case 1, electrophysiological testing revealed fast non-decremental conduction over an anterograde short right posteroseptal AV-AP. During ablation, latent pre-excitation due to anterograde adenosine-sensitive slow decremental conduction over the same AV-AP manifested after eliminating its non-decremental conduction. Complete abolition of AP conduction was achieved by additional ablation. In Case 2, overt pre-excitation disappeared after the first ablation session for an anterograde short non-decremental right mid-septal AV-AP. However, latent pre-excitation due to markedly decremental conduction over the same AV-AP unmasked by intravenous adenosine and atrial pacing manoeuvers could be eliminated in a second session. DISCUSSION: This report describes unusual anterograde short non-decremental AV-APs, developing markedly slow adenosine-sensitive decremental conduction during ablation. Such AV-AP conduction properties due to RF injury may be overlooked and mask incomplete ablation and point-out careful testing including stimulation techniques and low and higher dose adenosine administration post-ablation.

Cardiac arrest teams and time of day: effects on surviving in-hospital resuscitation.

OBJECTIVES: Little is known about the factors that influence survival following in-hospital resuscitation, but previous investigations have suggested that in-hospital resuscitations outside of regular working hours are associated with worse survival rates. MATERIAL AND METHODS: In-hospital cardiac arrest teams at our hospital were instructed to complete a questionnaire following every emergency call between July 2011 and June 2013. Data on all resuscitation attempts were collected and analyzed. RESULTS: A total of 65 in-hospital resuscitations were recorded in 42 males (64.6%) and 23 females (35.4%) (mean age 72.0±14.3 years). A total of 54 (83.1%) cardiac arrests were witnessed; seven (10.8%) showed a shockable rhythm at the time of the first ECG. Resuscitation attempts lasted 29.3±41.3 minutes, and 4.1±3.1 mg epinephrine was given. Return of spontaneous circulation could be achieved in 38 patients (58.5%); 29 (44.6%) survived the first day, 23 (35.4%) the seventh day, and 15 patients (23.1%) were discharged alive. Significantly more in-hospital resuscitations were obtained for those performed during non-regular working hours (P<0.001), with higher neuron-specific enolase levels at 72 hours after resuscitation during nonregular working hours (P=0.04). Patients who were discharged alive were significantly younger (P=0.01), presented more often with an initial shockable rhythm (P=0.04), and had a shorter duration of resuscitation (P<0.001) with the need of a lower dose of epinephrine (P<0.001). DISCUSSION: Survival rates following in-hospital resuscitation were poor at any time, but appear to depend less on time-dependent effects of the quality of resuscitation and more on time-dependent effects of recognition of cardiac arrests.

Segment-orientated analysis of two-dimensional strain and strain rate as assessed by velocity vector imaging in patients with acute myocardial infarction.

AIMS: Strain rate imaging techniques have been proposed for the detection of ischemic or viable myocardium in coronary artery disease, which is still a challenge in clinical cardiology. This retrospective comparative study analyzed regional left ventricular function and scaring with two-dimensional strain (2DS) in the first 4 to 10 days after acute anterior myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 32 AMI patients with an LAD occlusion and successful reperfusion. The assessment of peak systolic 2DS and peak systolic strain rate (SR) was performed segment-oriented with the angle-independent speckle tracking algorithm Velocity Vector Imaging (VVI). The infarcted, adjacent and non-infarcted segments were revealed by late enhancement MRI (LE-MRI), which was used as reference for the comparison with 2DS. The infarcted segments showed a significant decrease of tissue velocities, 2DS and SR in comparison to the non-affected segments. CONCLUSION: 2DS and SR as assessed by VVI seem to be a suitable approach for echocardiographic quantification of global and regional myocardial function as well as a promising tool for multimodal risk stratification after anterior AMI.

Eighteen months follow-up of the clinical efficacy of the high density mesh ablator (HDMA) in patients with atrial fibrillation after pulmonary vein isolation.

PURPOSE: The high density mesh ablator (HDMA), a mesh electrode catheter using radiofrequency delivery for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), has been shown to have a high acute ablation success rate. The primary endpoint of our study was the efficacy of HDMA to maintain sinus rhythm (SR), and the secondary endpoint is its efficacy to reduce AF burden in an 18-month follow-up. METHODS: Forty-two patients with AF [25 patients with paroxysmal AF (PAF, 59.5%), 17 patients with persistent AF (persAF, 40.5%)], were followed up with 7-day Holter monitoring and anamnestic survey at 6 and 12 months after PVI. To evaluate symptomatic AF episodes after 12 months, we used data from further hospital stays or information given by phone. RESULTS: In 42 patients at intervals of 6 and 12 months, stable SR was documented in 7-day Holter monitoring in 18 patients (42.9%, 10/25 and 9/25 for PAF and 8/17 and 9/17 for persAF, respectively). Symptomatic episodes of AF were reported in 31 patients (73.8%, 18/25 for PAF and 13/17 for persAF). Re-ablation was performed in seven patients (3/25 for PAF and 4/17 for persAF) not yielding to stable SR. At an 18-month follow-up (12-29 months), AF recurrence persisted in all 42 patients; in four patients, a permanent pacemaker was implanted (9.5%). No complications attributable to the HDMA occurred in this series. CONCLUSIONS: Our findings suggest that the PVI using the HDMA is a safe method but yields to a high AF recurrence rate at long-term follow-up even after a second procedure with the same tool.

Contrast medium induced nephropathy in patients undergoing percutaneous coronary intervention for acute coronary syndrome: differences in STEMI and NSTEMI.

UNLABELLED: The aim of this study was to assess the incidence, clinical predictors, and outcome of patients developing contrast medium induced nephropathy (CIN) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). BACKGROUND: CIN is associated with significant higher morbidity and mortality after coronary intervention. Recently it was shown, that patients undergoing percutaneous coronary intervention for acute myocardial infarction have a significant higher risk of developing CIN. Non-ST-elevating myocardial infarction (NSTEMI) patients (pts) might be at an even higher risk developing CIN than patients with ST-elevating myocardial infarction (STEMI), because of presenting older and more often with diabetes. METHODS: In 392 consecutive ACS patients developing myocardial infarction and therefore undergoing emergent coronary angiography between October 2004 and March 2007, we measured serum creatinine concentration (Cr) at baseline and each day of the following 3 days. Contrast medium induced nephropathy was defined as an increase in Cr > 0.5 mg/dl. ACS was defined according to the guidelines of the German Society of Cardiology. RESULTS: Overall, 392 pts were included: 203 (51.8%) with STEMI and 189 (48.2%) with NSTEMI. Patients with STEMI developed more often a cardiogenic shock (18 vs. 6%; P < 0.001) whereas patients with NSTEMI were older (67 vs. 61 years; P < 0.001) and presenting with a higher co-morbidity. Forty-five (11.5%) pts developed CIN; 22 (10.8%) in the STEMI group and 23(12.2%) in the NSTEMI group (P = 0.75). Patients developing CIN presented a more complicated clinical course and a significantly longer hospital stay (14 vs. 10 days; P < 0.001). The mortality rate was also significantly higher (16 vs. 6%; P < 0.05). CONCLUSION: This prospective study showed no differences in the incidence of developing CIN in patients undergoing PCI for STEMI or NSTEMI, but the predisposing factors, however, differed significantly. Although STEMI patients needed significantly more contrast medium for revascularisation, they did not develop CIN more often. CIN was associated with higher in-hospital complication rate and mortality. Thus, better preventive strategies according to the different predisposing factors leading to CIN are needed to reduce morbidity and mortality, especially in high risk patients.

Segmental pulmonary vein isolation in atrial fibrillation: new insights from the high density mesh mapper technique in an electrophysiologically guided approach.

OBJECTIVE: As opposed to fundamental investigations into the nature of atrial fibrillation (AF) current clinical studies of AF ablation techniques sometimes only contain sparse information about the underlying electrophysiological properties. The purpose of this prospective, pilot study was to evaluate acute therapeutic success and clinical outcome after 6 month of segmental ostial ablation (SOA) using the High Density Mesh Mapper catheter (HDMM, BARD Electrophysiology, Lowell, MA, USA) for an electrophysiological guided approach. The HDMM is a novel, single expandable basket electrode catheter for high resolution recordings at the left atrium/pulmonary vein (PV) junction. METHODS: SOA was performed by irrigated radiofrequency (RF) application around the HDMM. Entry- and exit conduction block, as well as decreased local electrode amplitude, were endpoints for short-term successful ablation. RESULTS: Seventy-two patients with highly symptomatic paroxysmal AF (PAF; 47, 65.2%), persistent AF (12, 16.7%) and permanent AF (13, 18.1%) were studied. Entrance conduction block was obtained in 93%, exit conduction block in 81% of all PV. After 6 month no PV stenosis was observed, 62 patients (86.1%) improved clinically, whereas 52 patients (72.2%) were free from arrhythmias and sinus rhythm was present favoring patients with PAF. CONCLUSIONS: In this first prospective study of PV isolation using the HDMM, our findings suggest, that this method is safe and yields good primary success rates and favourable clinical outcome at 6 month. The new technology based on high resolution recordings, offers beside good anatomical orientation a direct electrophysiological control for monitoring of bidirectional conduction block.

Prevalence of ventricular discordance and its relation to functional capacity in idiopathic dilated cardiomyopathy.

INTRODUCTION: Although left ventricular (LV) dilatation is the most distinguishing morphologic feature of idiopathic dilated cardiomyopathy (IDC), right ventricular (RV) dilatation may variably contribute to total cardiac enlargement. The prevalence and functional importance of the relative degree of left and right ventricular dilatation has not been comprehensively studied using cardiac magnetic resonance imaging (MRI). METHODS: Our prospective study included 58 consecutive IDC patients with a LV ejection fraction <40% and NYHA functional class > or =2. MRI was performed with a 1.5 Tesla scanner for RV and LV dimensional and functional analysis. Cardiopulmonary exercise testing was used for evaluation of exercise capacity. Patients were grouped into tertiles based on the distribution of LV end-diastolic volume. RESULTS: Compared to control subjects a considerable heterogeneity in the relative degree of left and right ventricular dilatation was noted in IDC patients. Within the entire patient group, a strong correlation between the degree of ventricular volume discordance and the extent of LV enlargement was observed (r = 0.8; P < 0.001). Tertile analysis revealed that the LV/RV volume ratio significantly differed in the three subgroups of patients (1.0 +/- 0.3 vs. 1.5 +/- 0.4 vs. 2.1 +/- 0.9; P < 0.001). Only weak correlations between MRI data and patients' functional capacity were found. LV ejection fraction was identified as the only independent predictor of maximum oxygen consumption in our setting. CONCLUSION: In IDC patients the degree of ventricular volume discordance is strongly related to the extent of left ventricular enlargement. However, comprehensive biventricular assessment of cardiac function by MRI adds little to our understanding of the cardiac mechanisms limiting exercise tolerance when compared to exclusive left ventricular measurements.

Massive pericarditis constrictiva calcarea with compression of the right ventricle and consecutive pulmonary embolism.

A 40-year-old man was admitted with a massive pericarditis constrictiva calcarea. Transthoracic and transoesophageal echocardiography demonstrated a double-layered pericardial calcification with interspacial effusion, a massive compression of the right ventricle, and a thrombus formation in the ventricle. In addition, severe pulmonary embolism due to this right ventricular thrombus formation was diagnosed by CT. This case demonstrates the importance of a multimodal imaging approach (echocardiography, TDI, MRI, CT) in the diagnosis of constrictive pericarditis and pericardial masses. In respect to the severe pericardial calcification with the massive interspacial mass, and the compression of the right ventricle with thrombus formation and consecutive pulmonary embolism, this case appears to be a very rare and uncommon clinical finding.

First experiences for pulmonary vein isolation with the high-density mesh ablator (HDMA): a novel mesh electrode catheter for both mapping and radiofrequency delivery in a single unit.

BACKGROUND: Interventional therapy of atrial fibrillation (AF) is often associated with long examination and fluoroscopy times. The use of mapping catheters in addition to the ablation catheter requires multiple transseptal sheaths for left atrial access. OBJECTIVES: The purpose of this prospective study was to evaluate feasibility and safety of pulmonary vein (PV) isolation using the high-density mesh ablator (HDMA), a novel single, expandable electrode catheter for both mapping and radiofrequency (RF) delivery at the left atrium/PV junctions. METHODS: Twenty-six patients with highly symptomatic paroxysmal AF (14, 53.8%) and persistent AF (12, 46.2%) were studied. Segmental PV isolation via the HDMA was performed using a customized pulsed RF energy delivery program (target temperature 55-60 degrees C, power 70-100 W, 600-900 seconds RF application time/PV). RESULTS: All 104 PVs in 26 patients could be ablated by the HDMA. Segmental PV isolation was achieved with a mean of 3.25 +/- 1.4 RF applications for a mean of 603 +/- 185 seconds. Entrance conduction block was obtained in 94.2% of all PV. The mean total procedure and fluoroscopy time was 159.0 +/- 32 minutes and 33.5 +/- 8.6 minutes, respectively. None of the patients experienced severe acute complications. After 3 months no PV stenosis was observed, and 85.6% and 41.6% of the patients with PAF and persistent AF, respectively, did not report symptomatic AF. CONCLUSIONS: In this first study of PV isolation using the HDMA, our findings suggest that this method is safe and yields good primary success rates. The HDMA simplifies AF ablation, favorably impacting procedure and fluoroscopy times.

Impact of irrigated energy application on the right coronary artery hemodynamics: FFR measurement in patients who underwent ablation of common type atrial flutter.

OBJECTIVE: The purpose of this first in vivo study was to assess the incidence of thermal influence to the right coronary artery (RCA) during ablation of common type atrial flutter (Aflu) by measuring the fractional flow reserve (FFR) in the vessel before, under and after ablation. METHODS: In thirty three patients ablated we performed coronary angiography (CA) before and at the end of the procedure. The FFR wire was positioned in the distal, the isthmus underlying, part of the RCA. Before and after the procedure FFR measurement was done at baseline and during adenosine administration. During the whole ablation procedure FFR measurement was continuously carried on, to monitor a transient thermal impact to the RCA. RESULTS: Of the 33 patients observed, 25 males, 8 females, mean age 58 +/- 9.5 years, none with CAD, all patients, except one with unidirectional block, were successfully ablated. The FFR at rest and under medication with adenosine before and after ablation was 0.985/0.949 and 0.981/0.942, respectively (p = ns). The CA of the RCA did not reveal any morphological change. The mean FFR while ablation declined from 0.94 to 0.904 (p = ns). Twenty-six patients (78.8%) had no or moderate decrease in FFR, seven patients (21.2%) demonstrated a substantial decrease [five patients (15.2%), FFR < 0.9 and >0.75] or significant change [two patients (6.1%)], FFR < 0.75 consistent with a remarkable or significant reduction of coronary flow. CONCLUSION: Ablation of AFlu did not alter RCA morphology; simultaneous FFR measurement showed severe depression of the FFR in a few patients, consistent with impairment in myocardial perfusion.

Quality of life and occurrence of atrial fibrillation in long-term follow-up of common type atrial flutter ablation: ablation with irrigated 5 mm tip and conventional 8 mm tip electrodes.

OBJECTIVES: The ablation of common type atrial flutter is mainly performed by two approved techniques, whose efficacy and outcome in terms of quality of life have not been evaluated so far in a long-term follow-up study over years. A high proportion of patients suffer from coexistent atrial fibrillation, which may worsen the ablation result. The question arises whether one technique is more effective than the other when immediate ablation results, the occurrence of atrial fibrillation and the quality of life are compared. Considering these facts, it is reasonable to think about new ablation strategies for common type atrial flutter in the era of new concepts in catheter ablation of atrial fibrillation. METHODS: In a retrospective study we evaluated a detailed questionnaire in 132 patients who underwent ablation of common type between 1999 and 2004. Radiofrequency ablation was performed irrespective of coexistent atrial fibrillation either with an irrigated tip or the 8 mm tip electrode. Acute and long-term ablation outcome, and the associated quality of life, pre-, under- and post-ablation was compared in the two different ablation groups. Recurrent tachycardia were re-evaluated by 12 lead ECG analysis and assessed for both ablation groups. RESULTS: 88 (67%) of the 132 patients contacted answered the questionnaire polling the perceived benefits of the procedure. Of the other 44 patients (33%); 4 (3%) had died, 7 (5.3%) had moved, 33 patients (25%) could not be included due to missing or incoherent answers. Independent of the ablation technique there was a high acute and long-term ablation success rate at about 95%. After a mean of 3 years of follow-up this benefit persists in spite of a high proportion of recurrent tachycardia, mainly atrial fibrillation (55/88 patients, 59.1%). Despite the occurrence of secondary tachycardia, there was a high significant long-term symptomatic benefit in the state of healthy and daily practice work, evaluated with a p-value of < 0.0005. The frequency of episodes and the symptom "tachycardia" were significantly reduced after effective ablation of common type atrial flutter, p-values of 0.003 and 0.002, respectively. Therefore the need for hospitalization was significant reduced (p = 0.001). Comparison of both approaches revealed that there was no significant difference related to the incidence and occurrence of atrial fibrillation. CONCLUSIONS: The two mainly accepted and applied techniques for the ablation of common type atrial flutter show an excellent outcome under the aspect of ablation efficacy and quality of life in longterm follow-up. Three years after the ablation procedure the majority of patients consider the intervention beneficial. Despite the relatively high appearance of atrial fibrillation in the long-term follow-up this effect is still traceable.

From atherosclerotic coronary ectasia to aneurysm: a case report and literature review.

In contrast to Kawasaki syndrome the formation of coronary aneurysms caused by atherosclerosis has hardly been demonstrated. We report on a 56-year old patient, admitted to our hospital for cardiovascular evaluation before carotid surgery. He had no anginal pain, but a history of coronary artery disease with previous anterior myocardial infarction. Angiography revealed a collateralized LAD occlusion. Myocardial scintigraphy only demonstrated fixed perfusion defects. Surprisingly, MR imaging revealed large coronary aneurysms of the RCX and RCA. Angiographic follow up showed a rapid progression of ectatic towards aneurysmatic coronary lesions within 3 years. General pathophysiological mechanisms promoting ectatic coronary artery disease as a structural failure of the atherosclerotic remodelling process itself and chronic dilatatory stimuli due to endogenous and exogenous factors are discussed.

[Inhibition of the muscarinic potassium current by KB130015, a new antiarrhythmic agent to treat atrial fibrillation]. / Inhibition des muskarinergen Kaliumionenstroms durch das neue Klasse-III-Antiarrhythmikum KB130015 im Vergleich zu Ibutilide.

BACKGROUND AND PURPOSE: Vagus-induced atrial fibrillation is of particular clinical interest. The muscarinic potassium current I(K(ACh)) mediates the induction of vagus-induced atrial fibrillation. Selective inhibition of I(K(ACh)) seems to be an option to treat atrial fibrillation. The application of amiodarone, presently one of the most important antiarrhythmic agents in the parmacological treatment of atrial fibrillation, is limited by its adverse effects. KB130015, a new amiodarone derivative, and ibutilide are new class III antiarrhythmic agents. METHODS: In guinea-pig atrial myocytes the muscarinic potassium current (I(K(ACh))) was activated by acetylcholine and adenosine. The effect of KB130015 on I(K(ACh)) was measured using the whole-cell voltage-clamp method. RESULTS: KB130015 and ibutilide in a concentration of 50 microM effectively inhibited the muscarinic potassium current. The effect was concentrationdependent and reversible. The half-maximum effective concentration was 0.8 microM (KB130015) and 2.8 microM (ibutilide). The inhibition of I(K(ACh)) was independent of the mode of its activation. The adenosine-induced ion current was as well inhibited by both drugs as the acetylcholine-induced ion current. Via GTP-gamma-S irreversibly activated I(K(ACh)) was also inhibited by KB130015 and ibutilide, whereas intracellular application showed no effect on I(K(ACh)). CONCLUSION: KB130015 and ibutilide are potent inhibitors of IK(ACh). Their effect is most likely mediated by direct interaction with the extracellular part of the ion channel. Acute effects of KB130015 on ventricular myocardium are not known so far. Ibutilide on the other hand is known to inhibit I(kr). KB130015 is a promising antiarrhythmic agent for the pharmacotherapy of vagus-induced atrial fibrillation.

How reliable is electrocardiography in differentiating transmural from non-transmural myocardial infarction? A study with contrast magnetic resonance imaging as gold standard.

Cardiovascular magnetic resonance (CMR) using contrast enhancement allows exact determination of the site and transmural extent of myocardial infarction (MI). We evaluated whether 12-lead electrocardiography can differentiate transmural from non-transmural MI or determine the site of MI by comparing the findings with those of contrast-enhanced CMR. A total of 27 patients (59.5+/-12.9 years) with a history of MI (6.4+/-2.9 months) underwent CMR (Magnetom, Siemens, Erlangen, Germany). Cine images were acquired in the horizontal and vertical long axes and short axis by TrueFISP. Contrast-enhanced CMR images were acquired in the same axes by segmented FLASH 15 min after administration of gadolinium-DTPA (0.15 mmol/kg). This showed the MI to be transmural in 11 patients and non-transmural in 16. An electrocardiogram (ECG) was recorded in all patients before CMR. T-wave alterations, descending ST-depression, pathological Q-waves and absent R waves were more frequent in non-transmural MI than transmural MI, as defined by contrast-enhanced CMR (p> or =0.618). However, none of the differences were statistically significant. R-wave reduction, q waves and horizontal ST-depression were more frequent in transmural than in non-transmural MI (p> or =0.157). Again, the differences were not significant. The sensitivity of the ECG for MI localization was highest in inferior infarctions (85.71%), the specificity was highest in anterior infarctions (100%), the best positive predictive value (80%) was achieved for anterolateral infarctions, and the best negative predictive value for lateral infarctions (95.83%). Transmural and non-transmural MI cannot be differentiated by ECG. The ECG is most accurate in detecting anterolateral MI.

[Perspectives and limitations in the treatment of vagus-induced atrial fibrillation. Insights from cellular pharmacology]. / Effektivität und Proarrhythmie bei der pharmakologischen Behandlung des vagal induzierten Vorhofflimmerns. Erkenntnisse aus der zellulären Pharmakodynamik.

BACKGROUND AND PURPOSE: Pharmacological treatment of atrial fibrillation (AF) is limited by induction of malignant ventricular arrhythmias. Developing new drugs, a promising strategy is a more specific treatment of the atria. Muscarinic potassium current (IK[ACh]) is predominantly expressed in supraventricular tissue and mediates the induction of vagus-induced AF. The authors investigated the profile of representative class III drugs in respect to their effect on IK(ACh). METHODS: In rat atrial myocytes, IK(ACh) was activated by acetylcholine (ACh) measured with the whole-cell voltage clamp method. Drugs used: selective IKs blocker chromanole 293B (Cro); IKr blockers sotalol (Sot), dofetilide (Dof), ibutilide (Ibu), and terikalant (Ter). Data are expressed as mean values +/- standard deviation (SD). RESULTS: ACh-induced IK(ACh) density was 73 +/- 9 pA/pF (n= 9). IK(ACh) was almost completely desensitized in the presence of 50 micro M Ter, Ibu, or Dof. IC(50) of IK(ACh) inhibition by the three drugs was 0.9, 2.8, and 4.2 micro M (Dof, Ibu, and Ter, respectively). Receptor-independent GTP-gamma-S-induced IK(ACh) was sensitive to Ter, Ibu, and Dof as well. Sot is known to be a weak inhibitor of IKr. Inhibition of IK(ACh) by Sot was much less potent (IC(50) = 35.5 micro M) than inhibition by the high-affinity IKr blockers Ter, Ibu, and Dof. Superfusion of the cells with the IKs blocker Cro showed no desensitization of IK(ACh). Applied via the patch pipette (< 40 min) none of the class III drugs were effective. CONCLUSION: The results indicate inhibition of IK(ACh) and IKr but not IKs to be of similar mechanism (direct ion channel inhibition from the external side of the membrane). Potent desensitization of muscarinic potassium current could be of clinical relevance especially in patients with vagus-induced AF.