OBJECTIVES: Anisotropic properties of cardiac tissue play an important role in initiation and perpetuation of ventricular tachycardia. However, anisotropic conduction properties in different morphologic types of chronic myocardial infarctions as well as frequency dependency still need to be elucidated. In the present study, the characteristics of anisotropic conduction were investigated in situ in the setting of ischemia-reperfusion induced chronic myocardial infarction. METHODS: Myocardial infarction was induced in 12 dogs by a percutaneous transcatheter left anterior descending coronary artery occlusion-reperfusion technique. Four additional dogs served as normal controls. After 14 to 20 days, epicardial mapping was performed using simultaneous unipolar recordings from 240 electrodes of a plaque electrode array placed on the epicardial border zone overlying the infarctions. Constant rate pacing with five cycle lengths (CL) ranging from 500 to 200 ms as well as programmed electrical stimulation (PES) with four basic cycle lengths (BCL) ranging from 430 to 300 ms and single extrastimuli (S2) were performed. RESULTS: Two anatomically different patterns of epicardial surface morphology were analyzed, designated as type I and type II. In seven animals, there was a continuous thin layer of surviving epicardial muscle fibers overlying the infarction (type I). During pacing with CL of 500 vs 200 ms, conduction velocity longitudinal to fiber orientation (theta L) decreased significantly in the infarcted animals compared to control group (10.9% vs 5.2%, p < 0.05) whereas conduction velocity transverse to fiber axis (theta T) decreased to a similar degree in control and infarcted animals (6.9 vs 7.4%, n.s.). After premature stimulation, there was considerably greater reduction in theta L in infarcted animals than in controls (39.8% vs 31.5%, p < 0.05) whereas theta T decreased to a similar extend in infarcted and control animals (22.2% vs 21.4%, n.s.). During constant rate pacing and premature stimulation, no functional conduction block was induced in type I infarctions. In five animals, the transmural infarctions clearly extended to the epicardial surface, but continuous strands of surviving epicardial muscle fibers traversed the area of necrosis (type II). During PES with S2, functional conduction block and areas of very slow conduction were observed in each case. CONCLUSIONS: In ischemia-reperfusion induced chronic myocardial infarctions, different epicardial patterns of morphology were observed. Anisotropic conduction was frequency dependent in the longitudinal but not in the transverse direction. In type I infarctions, functional conduction block was not inducible during PES whereas in type II infarctions, prerequisites for reentrant arrhythmias like functional conduction block and very slow conduction were induced in each case by single extrastimuli.

Animals↗

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The role of autonomic nervous system in the action of verapamil on the sinus node in man.

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Adult↗

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Influence of drugs on the relationship between sinus node recovery time and calculated sinoatrial conduction time in man.

Sinus node recovery time (SRT), the pacing rate with the maximal SRT, and calculated sinoatrial conduction time (SACT) were studied by overdrive atrial pacing and programmed premature atrial stimulation in 78 patients before and after the application of several antiarrhythmic drugs or of atropine. The maximum SRT was usually observed at lower rates of atrial pacing after application of a drug that prolonged SACT, whereas the opposite behaviour was observed in the majority of cases in whom the drug tested shortened calculated SACT. However, this relationship was not observed in all cases which may be due to random changes of sinus node automaticity or sinoatrial conduction, or to the inability of programmed premature atrial stimulation to detect changes of SACT. The results of this study further substantiate the importance of the properties of sinoat;ial conduction for achieving a maximal depression sinus node activity during high rate atrial pacing.

Anti-Arrhythmia Agents↗

PubMedDate not supplied

Simultaneous in utero assessment of AV nodal and ventricular electrophysiologic parameters in the fetal sheep heart.

BACKGROUND: Fetal tachyarrhythmias are usually of supraventricular origin. To investigate whether specific electrophysiologic properties of the fetal heart contribute to this preponderance by either favoring supraventricular tachycardias or by rendering ventricular tachycardias unlikely, we measured fetal electrophysiologic parameters in utero using transuterine fetal transesophageal electrocardiograms in fetal sheep. Since overdrive pacing may help to establish the mechanism of an arrhythmia and may be used to treat fetal tachycardias, different modes of transesophageal pacing in utero were also assessed. METHODS AND RESULTS: Decapolar electrophysiology catheters were fetoscopically inserted into the esophagus of 9 fetal sheep (pregnancy duration 94- 105 days, term = 145 days). Electrocardiograms were recorded simultaneously from all adjacent bipoles and from two pacing wires sutured onto the fetal shoulders. Pacing was attempted either via two adjacent electrodes of the intraesophageal catheter or via the most distal and most proximal electrode. Fetal cycle length, PQ, and QT intervals were close to (approx. 75 %), but fetal QRS duration was < 20 % of maternal values, thus shifting the relation between activation and repolarization towards longer excitation wave lengths. Fetal QT dispersion was small (< or = 10 ms). Atrial pacing was achieved in all fetuses using distant electrodes, and with lower thresholds when compared to closely spaced bipolar electrodes (p < 0.05). CONCLUSIONS: (I) An altered relation between ventricular activation and repolarization and a low dispersion of ventricular repolarization may protect the fetal heart against ventricular reentrant tachycardias. (II) Relatively normal fetal AV nodal conduction delay already provides one of the prerequisites for supraventricular reentrant tachycardias involving the AV node at this stage of fetal development. (III) High-rate esophageal pacing of the fetal atria is best achieved using widely spaced bipolar pacing electrodes.

Animals↗

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Lovastatin controls signal transduction in vascular smooth muscle cells by modulating phosphorylation levels of mevalonate-independent pathways.

Lovastatin has been proven to effectively lower circulating LDL cholesterol and to exert antiproliferative effects on various cell lines, the latter effect being only incompletely understood. We found that lovastatin modulates the signal transducing phosphorylation cascade in vascular smooth muscle cells in a mevalonate-independent manner. Lovastatin was found to distinctively increase total phosphotyrosine levels in smooth muscle cells, an effect which could not be restored by mevalonate. At a concentration of 5 micromol/L lovastatin had a highly specific effect on the mitogen-activated protein kinase pathway. The expression of p42/44 mitogen-activated protein kinase (MAPK) was clearly reduced, but could be restored by addition of mevalonate, while the phosphorylation of p44 was mildly suppressed and the phosphorylation of p42 MAPK was reduced to non-detectable levels. While the phosphorylation of p44 MAPK could partially be restored by addition of mevalonate, the reduced phosphorylation of p42 MAPK could not be restored by addition of excessive doses of mevalonate or stimulation of the cells with basic fibroblast growth factor. Concurrently the expression of the GTP-binding Ras protein was significantly elevated at 5 and 20 micromol/L lovastatin, this effect being attenuated by addition of mevalonate to cell cultures. The data indicate that lovastatin is capable of modulating cellular signaling independently of the cholesterol synthesis pathway.

Animals↗

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Nonpharmacological therapy for malignant ventricular arrhythmias: implantable defibrillator trials.

Implantable cardioverter-defibrillators (ICDs) are an important nonpharmacological option in the treatment of malignant ventricular arrhythmias. Technological advances in current devices permit nonthoracotomy implantation with transvenous lead systems using biphasic shocks. Decreasing device size has resulted in pectoral implantation. Battery longevity is still short in comparison with that of pacemakers. Lead failure rates as well as pacing thresholds are significantly higher than those for cardiac pacing lead systems. Other complications of ICD systems include infection, perforation, and thrombosis. The long-term performance of nonthoracotomy lead systems for ICD devices has now been extensively studied. Sudden death recurrence rates for these systems are less than 2% in 3 years and less than 5% at 5 years. Clinical trials with both monophasic and biphasic systems show a high degree of prevention of sudden death. Comparison of ICD outcome with that of drug therapy in three large retrospective studies and two small prospective randomized trials favors improved survival and sudden death prevention with device therapy. However, these studies need corroboration from large prospective trials. Two large prospective trials, CIDS and the AVID study, are now in progress to address this issue.

Amiodarone↗

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Comparison of the antiarrhythmic efficacy of disopyramide and mexiletine against stimulus-induced ventricular tachycardia.

Programmed ventricular stimulation was used to assess the effect of oral disopyramide (600 mg/day), mexiletine (600--1000 mg/day), and a combination of both drugs in a randomized cross-over study on 12 patients with documented ventricular tachycardia and/or fibrillation. In two cases, all three types of treatment were ineffective in that ventricular tachycardia could still be initiated under the same conditions. In four cases, disopyramide and mexiletine alone were ineffective or the change in inducibility was only slight. However, when both drugs were administered in combination, ventricular tachycardia was more difficult to induce or was no longer inducible. In two other cases, disopyramide was the more effective drug. In the remaining four patients, all three types of treatment were similarly effective. In patients whose ventricular tachycardia remained inducible its rate decreased from 188 +/- 45 bpm (control) to 170 +/- 40 bpm on disopyramide, 172 +/- 31 bpm on mexiletine, and 146 +/- 39 bpm on disopyramide plus mexiletine. Long-term therapy was based on the results of acute testing. Seven patients received both disopyramide and mexiletine and tolerated this therapy well during a follow-up of 42 +/- 23 weeks. Two sudden deaths occurred, one possibly due to dose reduction and one in a patient in whom short bursts of ventricular tachycardia remained inducible during acute testing. We conclude that the combined administration of disopyramide and mexiletine is effective and safe in patients with ventricular tachycardia. It is tolerated without major side effects even during long-term therapy.

Adult↗