Magnus Wilhelm Prull

Diadenosine-5-phosphate exerts A1-receptor-mediated proarrhythmic effects in rabbit atrial myocardium.

Diadenosine polyphosphates have been described to be present in the myocardium and exert purinergic‐ and nonreceptor‐mediated effects. Since the electrophysiological properties of atrial myocardium are effectively regulated by A1 receptors, we investigated the effect of diadenosine pentaphosphate (Ap5A) in rabbit myocardium. Parameters of supraventricular electrophysiology and atrial vulnerability were measured in Langendorff‐perfused rabbit hearts. Muscarinic potassium current (IK(ACh/Ado)) and ATP‐sensitive potassium current (IK(ATP)) were measured by using the whole‐cell voltage clamp method. Ap5A prolonged the cycle length of spontaneously beating Langendorff perfused hearts from 225±14 (control) to 1823±400 ms (Ap5A 50 μM; n=6; P<0.05). This effect was paralleled by higher degree of atrio‐ventricular block. Atrial effective refractory period (AERP) in control hearts was 84±14 ms (n=6). Ap5A1 μM reduced AERP (100 μM, 58±11 ms; n=6). Extrastimuli delivered to hearts perfused with Ap5A‐ or adenosine ( μM)‐induced atrial fibrillation, the incidence of which correlated to the concentration added to the perfusate. The selective A1‐receptor antagonist CPX (20 μM) inhibited the Ap5A‐ and adenosine‐induced decrease of AERP. Atrial fibrillation was no longer observed in the presence of CPX. The described Ap5A‐induced effects in the multicellular preparation were enhanced by dipyridamole (10 μM), which is a cellular adenosine uptake inhibitor. Dipyridamole‐induced enhancement was inhibited by CPX. Ap5A (1 mM) did neither induce IK(Ado) nor IK(ATP). No effect on activated IK(Ado/ATP) was observed in myocytes superfused with Ap5A. However, effluents from Langendorff hearts perfused with Ap5A 100 μM activated IK(Ado) by using A1 receptors. Ap5A did not activate A1 receptors in rabbit atrial myocytes. The Ap5A induced A1‐receptor‐mediated effects on supraventricular electrophysiology and vulnerability suggest that in the multicellular preparation Ap5A is hydrolyzed to yield adenosine, which acts via A1 receptors. An influence on atrial electrophysiology or a facilitation of atrial fibrillation under conditions resulting in increased interstitial Ap5A concentrations might be of physiological/pathophysiological relevance.

Propranolol inhibits IK(Ado) by competetive A1-receptor interaction

Propranolol ist einer der am meisten verwendete β-Blocker in der Klinik und wird experimentell als Antiadrenergikum genutzt. In der Literatur wurde berichtet, dass in bestimmten Patientenkollektiven die Inzidenz von Vorhofflimmern unter Propranolol abnimmt. Seine antiischämischen Eigenschaften sollen antiarrhythmisch wirken. Da die Aktivierung des muskarinergen Kaliumstroms (IK(ACh)) und des ATP abhängigen Kaliumstroms (IK(ATP)) Vorhofflimmern begünstigt, untersuchten wir die Wirkung von Propranolol auf den IK(ACh) und den IK(ATP). Der IK(ACh) wurde mittels Adenosin (Ado) oder Azetylcholin (ACh) aktiviert. Wir nutzten das „whole-cell voltage clamp“ Verfahren zur Erfassung der Ionenströme an isolierten Vorhofmyozyten von Ratten. Angaben erfolgen als Mittelwerte ±SD. Propranolol 50 μM sowie (+)-Propranolol (ein Isomer ohne β-blockierende Eigenschaften) hemmte den IK(Ado) vollständig (n = 6), hingegen war Esmolol signifikant schwächer wirksam. Der IC50 betrug 7 μM (n = 7). Die Strom-Spannungsbeziehung des gehemmten Stromes zeigte eine streng einwärts gleichrichtende Eigenschaft, die typisch für den muskarinergen Kaliumstrom ist. Die Inhibition war innerhalb von wenigen Sekunden reversibel. Der Effekt auf den Azetylcholin und GTP-γ-S induzierten muskarinergen Kaliumstrom war geringer (EC50 29 bzw. 31 μM), die intrazelluläre Applikation von Propranolol zeigte keinerlei Wirkung. Der IK(ATP) war kaum Propranolol sensitiv. Propranolol hemmt den IK(Ado) unabhängig von der Aktivität der G-Protein gekoppelten Rezeptoren. Die Inhibition ist nicht an die β-blockierende Eigenschaft der Substanz gebunden und daher unabhängig von der Anwesenheit von β-Mimetika. Der Adenosin induzierte IK(Ado) ist besonders empfindlich; es erscheint eine direkte Hemmung auf A1-Rezeptorebene wahrscheinlich. Als eine Ursache einer Propranolol bedingten Reduktion der Inzidenz von Vorhofflimmern ist die Hemmung des IK(ACh) denkbar. Bei der Anwendung von Propranolol in experimentellen kardiologischen Studien sollte eine mögliche Hemmung des IK(ACh) bei der Interpretation der Resultate berücksichtigt werden. Betablocking agents are known to exert anti-arrhythmic effects in ischemic myocardium due to blockade of myocardial beta-1-receptors. Since adenosine (Ado) induced muscarinic potassium current (IK(Ado)) and ATP sensitive potassium current (IK(ATP)) are discussed to be activated during ischemia we studied the effect of propranolol on IK(Ado) and IK(ATP). The effect of propranolol on muscarinic potassium current and IK(ATP) was studied in isolated rat atrial myocytes by means of the whole-cell voltage clamp tech- nique. Propranolol (50 μM) completely inhibited IK(Ado). IC50 was 7 μM. Inhibition of acetylcholine induced current (IK(ACh)) and GTP-γ-S induced muscarinic potassium current was less potent (IC50 29 μM and 31 μM respectively). Propranolol was active from the outside only. Intracellular application did not significantly affect muscarinic potassium current. (+)-propranolol, an isomer without beta-blocking properties, was as effective as (±)-propranolol. The inwardly rectifying potassium current IK(ATP) showed minor sensitivity to the compound (10% current reduction, propranolol 50 μM). Propranolol inhibits IK(Ado). Inhibition is not due to beta-receptor blockade. Predominantly an interaction with A1-receptors seems to be involved. The observations in part might explain the anti-arrhythmic properties of the drug in ischemic/fibrillating myocardium based on the prolongation of refractoriness.

Radiofrequency ablation of a left lateral atrioventricular accessory pathway in a 13-year-old boy with a criss-cross heart guided by nonfluoroscopic imaging

We present the first description of successful radiofrequency (RF) ablation of a bidirectional atrioventricular accessory pathway (AP) guided by nonfluoroscopic mapping with use of three-dimensional magnetic resonance imaging integrated into the Nav-X system (MRI/Nav-X fusion) in a 13-year-old boy with remote surgical palliation for cyanotic criss-cross heart with atrioventricular discordance, double-outlet right ventricle, and a large ventricular septal defect. Due to complex anatomy, a unique finding was that the eliminated left lateral AP electrically connected the left atrium to the antero-superior morphologic right ventricle prior to ablation.

Inhibition des muskarinergen Kaliumionenstroms durch das neue Klasse-III-Antiarrhythmikum KB130015 im Vergleich zu Ibutilide

ZusammenfassungHintergrund und Ziel:Bei Erwachsenen ist das vagale Vorhofflimmern von besonderer klinischer Relevanz. Pathophysiologisch ist der muskarinerge Kaliumionenstrom IK(ACh) ursächlich an der Entstehung des vagal induzierten Vorhofflimmerns beteiligt. Die selektive Inhibition des IK(ACh) erscheint therapeutisch vielversprechend. Die Anwendung von Amiodaron, dem derzeit wichtigsten Wirkstoff in der Therapie des Vorhofflimmerns, wird durch ein komplexes Nebenwirkungsprofil limitiert. KB130015, ein neues Amiodaronderivat, und Ibutilide sind neue Klasse-III-Antiarrhythmika.Methodik:Mittels der “whole-cell voltage-clamp”-Technik wurde die Wirkung von KB130015 und Ibutilide auf den muskarinergen Kaliumionenstrom an isolierten atrialen Myozyten von Meerschweinen untersucht.Ergebnisse:50 µM KB130015 und 50 µM Ibutilide inhibierten den IK(ACh) vollständig und reversibel. Die benötigte Konzentration für eine halbmaximale Inhibition des IK(ACh) betrug für KB130015 0,8 µM und für Ibutilide 2,8 µM. Die Hemmung des IK(ACh) war unabhängig vom Modus seiner Aktivierung. Sowohl der adenosin- als auch der acetylcholininduzierte Ionenstrom waren durch beide Wirkstoffe supprimierbar. Ebenso inhibierten beide Substanzen auch den durch GTP-γ-S irreversibel induzierten Ionenstrom. Intrazelluläre Applikation zeigte dagegen keinen Effekt auf den IK(ACh).Schlussfolgerung:KB130015 und Ibutilide sind potente Inhibitoren des IK(ACh). Eine direkte Hemmung des IK(ACh) durch Interaktion mit dem extrazellulär gelegenen Anteil des Ionenkanals ist wahrscheinlich. Akute Effekte von KB130015 auf das Ventrikelmyokard konnten bislang nicht nachgewiesen werden, Ibutilide dagegen inhibiert zusätzlich den IKr. KB130015 scheint daher das vielversprechendere der beiden Pharmaka zur Therapie des vagal induzierten Vorhofflimmerns zu sein. Eine signifikante Proarrhythmie ist im Vergleich zu Ibutilide nicht zu erwarten.AbstractBackground and Purpose:Vagus-induced atrial fibrillation is of particular clinical interest. The muscarinic potassium current IK(ACh) mediates the induction of vagus-induced atrial fibrillation. Selective inhibition of IK(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 (IK(ACh)) was activated by acetylcholine and adenosine. The effect of KB130015 on IK(ACh) was measured using the whole-cell voltage-clamp method.Results:KB130015 and ibutilide in a concentration of 50 µM effectively inhibited the muscarinic potassium current. The effect was concentrationdependent and reversible. The half-maximum effective concentration was 0.8 µM (KB130015) and 2.8 µM (ibutilide). The inhibition of IK(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-γ-S irreversibly activated IK(ACh) was also inhibited by KB130015 and ibutilide, whereas intracellular application showed no effect on IK(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 Ikr. KB130015 is a promising antiarrhythmic agent for the pharmacotherapy of vagus-induced atrial fibrillation.

Earliest Bedside Assessment of Hemodynamic Parameters and Cardiac Biomarkers: Their Role as Predictors of Adverse Outcome in Patients with Septic Shock.

Background: Early assessment and aggressive hemodynamic treatment have been shown to increase the survival of patients in septic shock. Current and past sepsis guidelines recommend a resuscitation protocol including central venous pressure (CVP), mean arterial blood pressure (MAP), urine output and central venous oxygen saturation (ScvO2) for resuscitation within the first six hours. Currently, the established severity score systems like APACHE II score, SOFA score or SAPS II score predict the outcome of critically ill patients on the bases of variables obtained only after the first 24 hours. The present study aims to evaluate the risk of short-term mortality for patients with septic shock by the earliest possible assessment of hemodynamic parameters and cardiac biomarkers as well as their role for the prediction of the adverse outcome. Methods: 52 consecutive patients treated for septic shock in the intensive care unit of one centre (Marien Hospital Herne, Ruhr University Bochum, Germany) were prospectively enrolled in this study. Hemodynamic parameters (MAP, CVP, ScvO2, left ventricular ejection fraction, Hematocrit) and cardiac biomarkers (Troponin I) at the ICU admission were evaluated in regard to their influence on mortality. The primary endpoint was all-cause mortality within 28 days after the admission. Results: A total of 52 patients (31 male, 21 female) with a mean age of 71.4±8.5 years and a mean APACHE II score of 37.0±7.6 were enrolled in the study. 28 patients reached the primary endpoint (mortality 54%). Patients presenting with hypotension (MAP <65 mmHg) at ICU admission had significantly higher rates of 28-day mortality as compared with the group of patients without hypotension (28-day mortality rate 74 % vs. 32 %, p<0.01). Furthermore, the patients in the hypotension present group had significantly higher lactate concentration (p=0.002), higher serum creatinin (p=0.04), higher NTproBNP (p=0.03) and after the first 24 hours higher APACHE II scores (p=0.04). A MAP <65 mmHg was the only hemodynamic parameter significantly predicting the primary endpoint (OR: 4.1, CI: 1.1 - 14.8, p=0.008), whereas the remaining hemodynamic variables CVP, ScvO2, Hematocrit, Troponin I and left ventricular ejection fraction (LVEF) seemed to have no influence on survival. Besides, non-survivors had a significantly higher age (74.1±9.0 vs. 68.4±6.9, p=0.01). If hypotension coincided with an age ≥72 years, the 28-day mortality rate escalated to 88%. Conclusions: In our study, we identified a risk group with an exceedingly high mortality rate: the patients with an age ≥72 years and presenting with hypotension (MAP <65 mmHg). These data can be easily obtained at the time of the very first patient contact. As a result, an aggressive and a more effective treatment can be initiated within the first minutes of the primary care, possibly reducing organ failure and short-term mortality in this risk group.

Dünndarm-Perforation durch einen verschluckten Tabletten-Blister nach postinterventioneller Koronarperforation

HISTORY AND ADMISSION FINDINGS A 70-year-old woman was admitted to hospital with progressive chest pain. Coronary angiography demonstrated a significant stenosis of the left descending artery (LAD), which was treated by percutaneous coronary intervention (PCI) and stent implantation. During this intervention, a coronary perforation occurred which was remedied immediately. Five days after the intervention, the patient complained about severe atypical chest and abdominal pain with nausea and vomitting, but no fever. Physical examination revealed an acute abdomen of uncertain origin. INVESTIGATIONS Laboratory tests revealed leukocytosis and elevated levels of C-reactive protein while cardiac enzymes were in normal range. The electrocardiogram showed no signs of acute myocardial ischemia. Abdominal x-ray was performed without any pathological findings. Further diagnostic tests, especially computed tomography of the abdomen, revealed an ingestion of a blister-wrapped tablet which had caused small bowel perforation and peritonitis. DIAGNOSIS, TREATMENT AND COURSE An acute abdomen due to ingestion of a foreign body was diagnosed and an emergency laparotomy was performed immediately. The blister pack was removed by ileostomy. The further course was uneventful. CONCLUSION The clinical presentation of abdominal pain is a frequent medical condition in hospital. Determining the cause requires precise assessment and examination and implicates a variety of differential diagnosis including non-cardiac and cardiac pain. Iatrogenic causes must be considered in differential diagnosis.

Vascular complications of percutaneous transradial coronary angiography and coronary intervention

ZusammenfassungHintergrund und Ziel:Vaskuläre Komplikationen nach transradialer Koronarangiographie und Koronarintervention können dramatische Folgen für die Durchblutung der Hand haben. Schwerwiegende Folgen (Handischämie mit Verschluss der Fingerarterien) nach Kanülierung der A. radialis sind bisher nur kasuistisch beschrieben. Die vorliegende Untersuchung soll klären, ob die perkutane transradiale Koronarangiographie/-intervention zu vaskulären Komplikationen führt.Patienten und Methodik:93 Patienten wurden in einem Zeitraum von 4 Monaten konsekutiv in die vorliegende Studie eingeschlossen und sowohl vor als auch nach der Herzkatheteruntersuchung/-intervention untersucht. Gefäßweite, Blutfluss, Flussgeschwindigkeiten und Verschlussdruckwerte wurden mittels Duplexsonographie und Verschlussdruckplethysmographie registriert. Die Stenosegraduierung erfolgte mit der „peak velocity ratio“-Methode.Ergebnisse:Bei 93 Patienten (75 Männer, mittleres Alter 62,5 Jahre) wurde bei unauffälligem Allen-Test eine transradiale Koronarangiographie oder -intervention durchgeführt. Die prozedurale Erfolgsrate lag bei 97,2%. Bei drei Patienten (2,8%) konnte die Untersuchung nicht erfolgreich durchgeführt werden. Der mittlere Gefäßdurchmesser nahm von 2,46 ± 1,7 mm (Standardabweichung [SD]) vor der Intervention auf 2,78 ± 0,69 mm (SD) nach der Intervention statistisch signifikant (p = 0,002) zu. Nicht signifikante Änderungen wurden bei Blutfluss, Flussgeschwindigkeiten und Verschlussdruckwerten registriert. Neun von 93 Patienten (10%) wiesen duplexsonographisch vaskuläre Komplikationen nach der transradialen Herzkatheteruntersuchung/-intervention auf. Kein Patient beklagte Beschwerden. Trotz vaskulärer Komplikationen traten bei keinem Patienten Perfusionsausfälle der Digitalarterien auf.Schlussfolgerung:Die transradiale Koronarangiographie und Koronarintervention ist für die Patienten eine sichere Methode mit einer hohen prozeduralen Erfolgsrate.AbstractBackground and Purpose:Vascular complications following transradial coronary angiography and coronary intervention could severely compromise perfusion of the hand. Drastic complications after cannulation of the radial artery (ischemia of the hand with occlusion of the digital arteries) are published only in brief reports. This study investigates whether percutaneous transradial artery coronary angiography/intervention results in vascular complications.Patients and Methods:93 patients were consecutively studied over a 4-month period. The following data were recorded before and after coronary angiography and/or intervention: diameter of the radial artery, blood volume, flow velocity, and occlusion pressure. Graduation of the stenosis after intervention was done according to the principle of the peak velocity ratio.Results:A transradial coronary angiography/intervention was performed in 93 patients (75 men, mean age 62.5 years) in case of an unremarkable Allen test. Procedural success rate was 97.2%. The intervention could not be completed successfully in three patients (2.8%). Mean vessel diameter increased from 2.46 ± 1.7 mm (standard deviation [SD]) before intervention to 2.78 ± 0.69 mm (SD) after intervention; this increase was statistically significant (p = 0.002). Changes in blood flow, flow velocity and occlusion pressure did not reach significance. Vascular complications were seen in nine of 93 patients (10%) after the procedure. No patient mentioned discomfort. No perfusion deficit of the digital arteries was seen.Conclusion:The transradial coronary angiography and intervention is a safe method with a high procedural success rate.

Breitkomplextachykardie bei einem jungen Mann

ZusammenfassungAnamneseWir berichten den Fall eines 24-jährigen Patienten mit Tachykardie und Dyspnoe. Der halbautomatische Defibrillator erkannte einen schockbaren Rhythmus: Kammerflimmern oder Kammertachykardie. Obwohl diese Diagnose falsch war, war die Therapie korrekt.DiagnoseVorhofflimmern beim Wolff-Parkinson-White Syndrom kann zu schnellen und unregelmäßigen Kammererregungen führen. Die typischen EKG-Veränderungen (tachykard, breiter QRS-Komplex, unregelmäßiges RR-Intervall), im englischen „fast, broad and irregular“, haben dieser Tachykardie den Namen FBI-Tachykardie eingebracht. Oft ist es eine Blickdiagnose. Aufgrund des Risikos, in Kammerflimmern zu degenerieren handelt es sich um eine potenziell lebensbedrohliche Situation.AbstractAnamnesisWe report a case of a 24-year-old man suffering from tachycardia and dyspnea. A semi-automatic defibrillator assessed him to have a shockable rhythm: ventricular fibrillation or ventricular tachycardia. Although the diagnosis was wrong the patient was treated correctly.DiagnosisAtrial fibrillation in Wolff-Parkinson-White syndrome can result in a rapid and irregular ventricular response. Because of its characteristic electrocardiograph (ECG) features (fast, broad and irregular) this tachyarrhythmia has been named FBI tachycardia. It can often be diagnosed at the first glance. As it carries the risk to deteriorate into ventricular fibrillation it is a potentially life-threatening clinical condition.

Angeborenes linksventrikuläres Aneurysma bei einem 17-jährigen Leistungssportler@@@Congenital left ventricular aneurysm in a 17-year-old competitive athlete

We present the case of a 17-year-old competitive athlete with an asymptomatic left ventricular aneurysm (LVA). Echocardiography demonstrated hypoplasia of the septum and a large apical LVA. Magnetic resonance imaging (MRI) detected a very thin and fibrotic wall of the LVA. Due to the potential risk of rupture the LVA was surgically resected and the apex of the left ventricle was covered with a patch plasty. The patient had an event-free postoperative course. Because of the potential risk of arrhythmia, the patient was recommended not to participate further in competitive sport.ZusammenfassungWir berichten über einen 17-jährigen Leistungssportler mit einem asymptomatischen, kongenitalen linksventrikulären Aneurysma (LVA). Die Echokardiographie wies eine Hypoplasie des apikalen Septums und ein ausgedehntes, zipfelförmiges LVA im Bereich der Apex nach. Das MRT zeigte eine sehr dünne und fibröse Wand des LVA. Aufgrund dieses Befunds wurde bei mutmaßlich erhöhtem Risiko einer Ruptur des LVA eine chirurgische Resektion des Aneurysmas mit anschließender Patch-Plastik durchgeführt. Der postoperative Verlauf verlief komplikationslos, trotzdem wurde dem Patienten zunächst von einer Fortsetzung seines Wettkampfsports abgeraten.AbstractWe present the case of a 17-year-old competitive athlete with an asymptomatic left ventricular aneurysm (LVA). Echocardiography demonstrated hypoplasia of the septum and a large apical LVA. Magnetic resonance imaging (MRI) detected a very thin and fibrotic wall of the LVA. Due to the potential risk of rupture the LVA was surgically resected and the apex of the left ventricle was covered with a patch plasty. The patient had an event-free postoperative course. Because of the potential risk of arrhythmia, the patient was recommended not to participate further in competitive sport.

Angeborenes linksventrikuläres Aneurysma bei einem 17-jährigen Leistungssportler

We present the case of a 17-year-old competitive athlete with an asymptomatic left ventricular aneurysm (LVA). Echocardiography demonstrated hypoplasia of the septum and a large apical LVA. Magnetic resonance imaging (MRI) detected a very thin and fibrotic wall of the LVA. Due to the potential risk of rupture the LVA was surgically resected and the apex of the left ventricle was covered with a patch plasty. The patient had an event-free postoperative course. Because of the potential risk of arrhythmia, the patient was recommended not to participate further in competitive sport.ZusammenfassungWir berichten über einen 17-jährigen Leistungssportler mit einem asymptomatischen, kongenitalen linksventrikulären Aneurysma (LVA). Die Echokardiographie wies eine Hypoplasie des apikalen Septums und ein ausgedehntes, zipfelförmiges LVA im Bereich der Apex nach. Das MRT zeigte eine sehr dünne und fibröse Wand des LVA. Aufgrund dieses Befunds wurde bei mutmaßlich erhöhtem Risiko einer Ruptur des LVA eine chirurgische Resektion des Aneurysmas mit anschließender Patch-Plastik durchgeführt. Der postoperative Verlauf verlief komplikationslos, trotzdem wurde dem Patienten zunächst von einer Fortsetzung seines Wettkampfsports abgeraten.AbstractWe present the case of a 17-year-old competitive athlete with an asymptomatic left ventricular aneurysm (LVA). Echocardiography demonstrated hypoplasia of the septum and a large apical LVA. Magnetic resonance imaging (MRI) detected a very thin and fibrotic wall of the LVA. Due to the potential risk of rupture the LVA was surgically resected and the apex of the left ventricle was covered with a patch plasty. The patient had an event-free postoperative course. Because of the potential risk of arrhythmia, the patient was recommended not to participate further in competitive sport.