Johannes Brachmann

Implantable Cardioverter Defibrillator: Possible Hazards of Electromagnetic Interference

We report on three patients with an automatic, implantable Cardioverter defibrillator (AICD, CPI) in whom the device had been deactivated due to electromagnetic interference. In all cases, the source of the electromagnetic disturbances could be identified.

Circus movement atrial flutter in the canine sterile pericarditis model. Relation of characteristics of the surface electrocardiogram and conduction properties of the reentrant pathway.

OBJECTIVES This study was designed to elucidate the basis for the electrocardiographic (ECG) appearance of atrial flutter in the canine sterile pericarditis model. BACKGROUND During atrial flutter, the surface ECG may show typical F waves or isolated P waves of any polarity. METHODS Electrocardiographic leads II, III and aVF and epicardial atrial activation maps constructed from 127 simultaneously recorded bipolar electrograms were compared in 20 dogs with sterile pericarditis and inducible atrial flutter. RESULTS In 10 dogs with F wave atrial flutter, single loop reentry occurred around combined functional/anatomic obstacles that included one or both caval veins and a vertically oriented arc of functional conduction block. In 10 dogs with P wave atrial flutter, a merely functional (n = 4) or combined (n = 6) obstacle involving any atrial vessel and more vertically (n = 5) or more horizontally (n = 5) oriented arcs of block was present. The isoelectric interval between P waves corresponded to the conduction time within the slow zone of the reentrant circuit (96 +/- 27 vs. 100 +/- 24 ms, mean +/- SD). Slow conduction accounted for 65 +/- 8% of the cycle length in P wave atrial flutter, but for only 29 +/- 7% in F wave atrial flutter (p < 0.05). Slow conduction was usually associated with activation of fewer than five epicardial electrodes per 10-ms isochronal interval, reflecting only a small amount of atrial tissue. The polarity of P or F waves was determined by the direction of the major wave front activating the most electrodes per 10-ms isochronal interval, irrespective of whether the right or the left atrium was activated. CONCLUSIONS The F waves result from reentrant activation at a relatively constant speed around a vertically oriented functional/anatomic obstacle involving one or both caval veins. The P waves occur when the circuit contains a marked area of slow conduction.

Differential Rate and Potassium-Dependent Effects of the Class III Agents d-Sotalol and Dofetilide on Guinea Pig Papillary Muscle

The class III agents d-sotalol and dofetilide have been shown to exhibit differential effects in large controlled clinical trials. The aim of this study was to investigate the basic electrophysiological properties of these two antiarrhythmia agents in an in vitro experimental model with regard to potential antiarrhythmic and proarrhythmic action. Using standard microelectrode techniques, we evaluated the electrophysiological effects of d-sotalol and dofetilide on action potential parameters recorded from guinea pig papillary muscle at 2.5 mM, 3.5 mM, and 5.6 mM extracellular potassium concentrations. The following parameters were recorded: resting membrane potential (RMP), action potential amplitude (APA), action potential duration at 90% repolarization (APD 90), and maximum upstroke velocity (Vmax). Under all conditions studied, both d-sotalol and dofetilide exhibited highly selective reverse rate-dependent class III action. In contrast to dofetilide, the class III activity of d-sotalol was markedly influenced by changes in extracellular potassium concentrations, predominantly at low pacing rates. Hypokalemia enhanced the action potential–prolonging effects of d-sotalol, whereas hyperkalemia diminished this effect. In addition, reverse rate dependence associated with dofetilide was significantly more pronounced than reverse rate dependence associated with d-sotalol. Our observations provide a potential electrophysiological basis for differential antiarrhythmic and proarrhythmic mechanisms associated with these two drugs.

Transesophageal echo phase imaging for localizing accessory pathways during adenosine-induced preexcitation in patients with the Wolff-Parkinson-White syndrome

Transesophageal phase images and precordial electrocardiography (ECG) were used to localize accessory pathways during adenosine-induced preexcitation in 30 patients (18 men, mean age +/- SD 33 +/- 14 years) undergoing endocardial mapping for suspected Wolff-Parkinson-White syndrome. Digitized 2-dimensional echocardiographic cine loops were mathematically transformed using a first harmonic Fourier algorithm before and after catheter ablation. Endocardial mapping found single accessory pathways with anterograde conduction in 20 patients, concealed pathways in 7, and atrioventricular reentry circuits in 3 patients. At baseline, precordial ECG correctly localized 8 pathways (40%) with anterograde conduction and predicted 5 adjacent locations (25%), but findings were normal in 7 patients (35%). Phase imaging correctly identified only 3 pathway locations (15%), findings were normal in 15 (75%), and could not be obtained in 2 patients (10%). Adenosine augmented manifest but minimal preexcitation in 9 patients and unmasked latent preexcitation in 7. In 4 patients, preexcitation was already maximal at baseline. During adenosine-augmented preexcitation, ECG correctly identified 13 locations (65%), but still predicted 7 adjacent locations (35%). However, phase imaging correctly identified 15 locations (75%) and predicted only 3 adjacent locations (15%). All midseptal (n = 2) and anteroseptal (n = 2) locations were correctly identified by phase imaging, but none by ECG. On follow-up studies in 16 patients, successful catheter ablation (n = 13) was equally well confirmed by ECG and phase imaging. Therefore, transesophageal echocardiographic phase imaging during adenosine-induced preexcitation is a readily available and safe procedure that appears clinically most useful for identifying septal pathways.

Echocardiographic Fourier phase and amplitude imaging for quantification of ischemic regional wall asynergy: An experimental study using coronary microembolization in dogs

OBJECTIVES This study investigated whether echocardiographic Fourier phase and amplitude imaging can be used to evaluate ischemia-related regional wall asynergy. BACKGROUND Because myocardial ischemia delays the onset and peak of endocardial inward motion and reduces its magnitude, Fourier phase and amplitude analysis of two-dimensional echocardiograms may be used to evaluate regional wall motion abnormalities objectively by analyzing temporal sequence and magnitude of endocardial motion. METHODS Digital cine loops of left ventricular long- and short-axis views were obtained in six anesthetized dogs at baseline and 1 to 30 min after coronary microembolization and were mathematically transformed using a first-harmonic Fourier algorithm to obtain phase angles and amplitudes of endocardial segments. Mean phase angles and amplitudes were compared with visual wall motion analysis based on a scoring system and quantitative analysis based on segmental fractional area shortening derived from planimetry. RESULTS Microembolization delayed segmental phase angles by 47 +/- 44 degrees in mild to moderate hypokinesia (fractional shortening [mean +/- SD] 41 +/- 13%) and by 77 +/- 63 degrees in severe hypokinesia (fractional shortening 13 +/- 5%) and reduced segmental amplitudes from 80 +/- 36 gray level intensity at baseline to 53 +/- 34 in segments developing mild to moderate hypokinesia, and from 93 +/- 36 to 35 +/- 28 gray level intensity in segments developing severe hypokinesia. Shifts in segmental phase angles correlated better with dynamic shifts in segmental fractional area shortening than did changes in wall motion score (r = -0.65 vs. r = 0.52, p < 0.001). CONCLUSIONS Echocardiographic Fourier phase imaging can be used to evaluate ischemia-related regional wall asynergy, displaying contraction sequence and magnitude in a simple, objective format.

Cardiac sympathetic nervous activity during myocardial ischemia, reperfusion and ventricular fibrillation in the dog--effects of intravenous lidocaine.

In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after occlusion of the left anterior descending coronary artery as well as during reperfusion and ventricular fibrillation (VF). In 7 control animals, CSNA did not significantly differ from preocclusion levels when determined 20 min after occlusion (+3.5 +/- 1.5%, mean +/- SEM) and up to 15 min following reperfusion (+1.5 +/- 0.6%). However, VF was associated with a potential increase in CSNA by 106 +/- 15.5% (p less than 0.001). The effect of lidocaine (6 mg/kg) on cardiac sympathetic tone was examined in 5 additional animals. Lidocaine reduced control CSNA by 23 +/- 4.7% (p less than 0.001); subsequent ischemia and reperfusion did not substantially change the level of preocclusion activity. CSNA decreased significantly also during VF (52 +/- 4.2%, p less than 0.001). In conclusion, efferent CSNA was slightly altered in the course of acute myocardial ischemia and reperfusion, but significantly increased during VF. Lidocaine produced marked attenuation of CSNA in anesthetized dogs.

Electrophysiological effects of E 4031, a drug with selective class III properties, in man.

We studied the electrophysiological effects ofE 4037, given in a dose ascending manner (1.5, 3.0, and 6.0 μg/kg over 5 min followed by 0.1, 0.2, and 0.4 μg/kg per min for 60 min, respectively) to 19 volunteers. There were significant, dose related linear increases in QT and QTC intervals, in atrial functional and effective refractory periods (ERPs) at a paced cycle length of 400 ms, and in ventricular functional and ERPs at a paced cycle length of 600 ms. There was no significant change in the AH and HV intervals or QRS duration. No significant proarrhythmic or other side effects were encountered during the administration of the drug. E 4031 prolongs atrial and ventricular refractoriness without significantly affecting AV or intraventricular conduction, consistent with selective Class III properties. At the doses used in the present study, intravenous infusion of E 4031 appears to be safe and well tolerated.

Differential effects of d-sotalol on normal and infarcted myocardium: an experimental study using epicardial mapping

OBJECTIVE The aim of the study was to investigate the differential effects of the class III agent, d-sotalol, on conduction and refractoriness on normal and infarcted areas of the canine ventricle. METHODS Epicardial mapping studies were performed in 6 dogs 5-7 days after ligation of the left descending coronary artery using a specially designed patch electrode which contained 192 bipolar electrodes. Normal and infarcted areas were differentiated with respect to their macroscopic appearance and electrophysiological properties. Activation maps and local effective refractory periods (ERP) were determined before and after the administration of d-sotalol (1.5 mg/kg) at cycle lengths of 250, 300 and 350 ms. RESULTS Conduction and refractoriness were relatively homogeneous in the normal zone (NZ), contrasting with inhomogeneity in the infarct zone (IZ). In 2 dogs d-sotalol produced regional delay and block of conduction, exclusively in the IZ. The relative increase in refractoriness (delta ERP) after d-sotalol was significantly more pronounced in the IZ than in vs the NZ. In the NZ, delta ERP was most prominent at the longest (350 ms) and least prominent at the shortest (250 ms) basic pacing cycle lengths (11.5 +/- 2.8 vs. 7.3 +/- 1.4%; P < 0.05). The effect of d-sotalol in the IZ was independent of the basic pacing cycle length. CONCLUSIONS d-Sotalol preferentially prolonged refractoriness in the IZ of the canine ventricle. This effect and the lack of rate-dependence in the IZ could provide a possible explanation for both the potent antiarrhythmic and potential antiarrhythmic effect of d-sotalol.

Electropharmacology of the bradycardic agents alinidine and zatebradine (UL-FS 49) in a conscious canine ventricular arrhythmia model of permanent coronary artery occlusion

SummaryMyocardial infarction was produced in 27 anesthetized dogs by ligating the left anterior descending (LAD) coronary artery proximal to the septal branch. Nineteen of these animals survived the operation and were studied by programmed stimulation in a random sequence between the third and seventh days after the infarct. Complete electrophysiologic testing was implemented in each animal prior to and after single doses of either alinidine (1 mg/kg IV) or zatebradine (0.5 mg/kg IV). Alinidine prevented reinduction of sustained ventricular tachycardia (SVT) in only 2 of 9 dogs and zatebradine in 1 of 8 dogs. The SVT cycle length was not significantly changed in all cases in which it was still inducible despite drug administration (p>0.05). Alinidine lengthened the effective refractory period (ERP) in the AV node (p<0.01), whereas zatebradine did not induce a statistically significant prolongation. Conversely, zatebradine increased the left ventricular ERP, while alinidine left it almost unchanged. The rate-corrected QT interval (QTc) did not significantly differ from control values after the administration of either agents. Also, the duration and the ERP of infarctzone potentials, defined as late potentials, remained unaltered. The results indicate that the bradycardic agents alinidine and zatebradine do not exert antiarrhythmic efficacy against SVT induced during subacute myocardial infarction in conscious dogs. None of these drugs substantially changed ventricular electrophysiology or showed a drug-specific proarrhythmic effect.

Significance of cardiac innervation on spontaneous ventricular arrhythmias elicited by left stellate ganglion stimulation in dogs 4 days after myocardial infarction: comparison of two experimental models.

SummaryThe effects of cardiac sympathetic overactivity on spontaneous arrhythmias and transmural left ventricular effective refractory period (LVERP) were assessed by left stellate stimulation (LSS) in 16 anesthetized dogs. The experiments were performed 4 days after proximal occlusion of the left anterior descending (LAD) coronary artery produced by either ligation (9 dogs) or embolization with histoacryl (7 dogs). The innervation of left ventricular myocardium was studied by light and electron microscopies. Synaptophysin (SYN)- and neuropeptide Y (NPY)- immunoreactive nerve fibers and terminals were thereby detected. In dogs subjected to ligation, LSS elicited negligible arrhythmias in spite of a decrease in LVERP by 6.9±2.2% (mean±SD, p<0.001). However, dogs with intravascular occlusion were more susceptible to LSS, as indicated by development of sustained ventricular rhythms. In these animals, the LVERP decreased with LSS by 14.6±3.4% (p<0.001). The innervation of the enterior left ventricular wall distal to the place of occlusion revealed a higher reduction of SYN- and NPY-immunoreactive nerves in infarcted myocardium and a more heterogeneous distribution of nerves in undamaged regions after ligation compared to intravascular occlusion. Ultrastructurally, nerve terminals containing small agranular and large dense-core vesicles were found innervating ischemically damaged myocardiocytes. Our findings indicate a higher preservation of nerves in infarcted and noninfarcted myocardium of animals subjected to embolic occlusion of the LAD. Because LSS apparently elicited more arrhythmias in these animals, we suggested a proarrhythmic effect of intact myocardial innervation after infarction.