title: Beta-adrenergic-mediated influences on microscopic conduction in epicardial regions overlying infarcted myocardium.
abstract: Slowing in conduction and functional block in the epicardial tissue overlying a region of transmural necrosis are pivotal in the genesis of many lethal arrhythmias during the healing phase of myocardial infarction. The mechanisms responsible for these alterations in conduction in the epicardial region have not been completely elucidated. In the present study, the microscopic abnormalities in conduction were investigated in vitro using high-density mapping with 224 bipolar electrodes (interelectrode distance, 350 microns) in isolated epicardial tissue excised from the hearts of dogs 2 weeks after anterior myocardial infarction. Seven epicardial tissue slices (group 1) exhibited uninterrupted sequential activation after stimulation at the basic cycle length as well as after premature stimuli. Four tissues (group 2) demonstrated microscopic alterations in conduction both during basic drive and premature stimuli, with the extent of conduction delay dependent on the stimulation site. In three tissues (group 3), the activation sequence was normal during the basic drive but became abnormal after premature stimulation, with the appearance of functional block in the direction transverse to fiber orientation. Superfusion with isoproterenol (10(-6) M) did not significantly modify resting membrane potential, amplitude, or maximum rate change of voltage (Vmax) of phase 0 depolarization but decreased action potential duration. Isoproterenol did not alter the activation sequence during basic drive, but it reduced the slowing in conduction elicited by premature stimulation in group 1 (p less than 0.01 in the transverse direction), alleviated microcircuitous conduction in group 2, and prevented the occurrence of functional block in tissues in group 3. Despite this salutary effect on conduction velocity, arrhythmias occurred after isoproterenol because of focal activity (three of 14, 21%) or reentry (one of 14, 7%) at very short coupling intervals of premature stimulation. These findings indicate that microscopic abnormalities in conduction occur in response to premature stimulation in epicardial regions overlying an infarct, eliciting conduction block that is more prone to occur in the direction transverse to fiber orientation and is dependent on the direction of activation. beta-Adrenergic stimulation prevents or attenuates the alterations in the pattern of activation elicited by premature stimulation. However, this potential beneficial effect of beta-adrenergic stimulation is offset by the occurrence of focal activity and reentry at short coupling intervals of premature stimulation.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Mo. 63110.
authors.forename: G
authors.initials: G
authors.lastname: Zuanetti
authors.forename: R H
authors.initials: RH
authors.lastname: Hoyt
authors.forename: P B
authors.initials: PB
authors.lastname: Corr
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D004285:Dogs; D004553:Electric Conductivity; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009203:Myocardial Infarction / Q000503:physiopathology*; D010496:Pericardium / Q000187:drug effects / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013997:Time Factors
chemical_list: D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol