摘要:

Shock Effects During Ischemia.Introduction: Defibrillation shocks produce extension of the myocardial action potential repolarization time (AP extension) in nonischemic myocardium. AP extension may synchronize repolarization in the heart because the extension increases when shock timing is increased. We tested whether AP extension occurs and whether it increases when shock timing is increased in regionally ischemic isolated perfused rabbit hearts stained with the transmembrane voltage sensitive fluorescent dye, di‐4‐ANEPPS and given diacetyl monoxime to eliminate motion artifacts.Methods and Results: Before and after left anterior descending (LAD) coronary artery occlusion, APs were recorded on the anterior left ventricular epicardium with an epifluorescence measurement system. Hearts were paced with a train of 10 stimuli (SI) and then during the 10th AP were given a defibrillation shock (S2) from epicardial electrodes on either side of the recording region. Before LAD occlusion, duration of the 9th SI‐induced AP measured at full repolarization was 171 ± 11 msec (mean ± SD). Within 15 minutes after LAD occlusion, the AP duration became shorter (P<0.05) and more variable (137 ± 42 msec), and APs with negligible plateaus were observed. Extension of the 10th AP by S2 was significant both before (mean extension of 59 to 65 msec for three S2 waveforms tested) and after LAD occlusion (mean extension of 35 to 41 msec). Unlike the results before LAD occlusion, AP extension after occlusion was independent of absolute shock timing expressed in msec. When timing was expressed as a fraction of individual AP durations, AP extension after occlusion increased with increases in shock timing.Conclusions: Shocks extend Aps during ischemia; however, absolute time dependence of AP extension is not constant among cells that have different AP durations during Ischemia. This may influence postshock repolarization synchrony when different AP durations exist in different parts of regionally ischemi

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00354.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Slow Recovery of INa.introduction: Recovery of the Na channel from inactivation is essential to the normal conduction and refractoriness of the myocardium. In addition to fast recovery, occurring within several milliseconds at hyperpolarized potentials, a component of the current exhibits slow recovery occurring over hundreds of milliseconds. Long conditioning depolarizations potentiate slow recovery.Methods and Results: This study was designed to test conditioning durations (tc) between 0.25 and 4 seconds (s) as to whether recovery was slowed by an effect on the fast (τt) and slow (τs) time constants of recovery, the relative amplitude of the slow component (As), or both. We studied Na channel recovery at ‐150 mV from inactivation using whole cell voltage clamp of rat ventricular cells at 23°C using a two‐pulse recovery protocol. Longer conditioning durations dramatically increased As, (from 12% for tc= 500 msec to 37% for tc= 4(MM) msec, P<0.01). Neither τt(6 vs 5 msec) nor τs, (115 vs 140 msec) were significantly affected. In a second set of experiments, the recovery potential was depolarized to a potential at which the sodium current was 70% available (≅‐105 mV). This recovery potential had no significant effect on As, but both τfand τswere significantly slower (e.g., at tc= 2s, τs= 147 msec and As, = 28% at Vr= ‐150 mV, and τs, = 456 msec and As, = 29% at Vr, ≅ ‐105 mV). In addition, a 1‐ to 2‐msec lag in the onset of recovery was prominent at the depolarized recovery potentials.Conclusions: Our results support a model for slow recovery where conditioning duration determines entry into an inactivated state from which Na channels recover slowly, and recovery potential determines the rate of recovery from this state. A kinetic scheme with at least three inactivated states is proposed. These results also have implications for cardiac excitability under conditions, such as ischemia, where

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00355.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Ca2+‐Loading and EAD.introduction: Our previous observations indicate that the Na2+:Ca2+exchange current (INa:Ca) plays an important role in early afterdepolarizations occurring at more negative Vm (L‐EAD). The purpose of these studies was to examine the role of Ca2+‐loading, which stimulates INa:Ca, in generation of L‐EAD.Methods and Results: Purkinje strands and preparations of ventricular myocardium from dogs and guinea pigs were superfused with oxygenated physiologic buffer solutions at 37°C, To induce EADs, [K+]0was reduced to 2.0 to 3.0 mM and [Cs+]0, (3.6 to 4.0 mM) was added at slow rates of ≤ 0.3 Hz. Isometric contraction in canine Purkinje strands and guinea pig papillary muscles doubled in 1‐hour exposure to Cs+and low [K+]0at slow rates, and the uptake of45Ca2+was approximately doubled after 30 minutes. Forty‐three percent of Purkinje fibers developed L‐EAD after a latent period of 17 to 123 minutes of exposure. Ouabain (0.2 μM) suppressed LEAD within 10 minutes reversibly. Ca2+‐loading (low [Na+]0or high [Ca2+]0for 5 to 10 minutes before exposure to Cs+, low [K+]0, and slow rates resulted in rapid development of L‐EAD in all preparations during subsequent exposure. In Ca2+‐loaded preparations, delayed afterdepolarizations (DADs) as well as L‐EADs developed.Conclusion: Reduction of K+currents with Cs+, low [K+]0, and slow rates induced L‐EAD in a fraction of Purkinje fibers after a latent period during which Ca2+‐loading of the sarcoplasmic reticulum occurred, while fibers preloaded with Ca2+developed L‐EAD rapidly and uniformly. These findings indicate that Ca2+‐loading is a critical condition for the development of L‐EAD. Early suppression of L‐EAD by ouabain suggests a dependence of L‐EAD on low [Na+]1. These findings imp

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00356.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Connexin Phenotypes in the Human Heart.Introduction: Gap junction channels are major determinants of intercellular resistance to current flow between cardiac myocytes. Alterations in gap junctions may contribute to development of arrhythmia substrates in patients. However, there is significant interspecies variation in the types and amounts of gap junction subunit proteins (connexins) expressed in disparate regions of mammalian hearts. To elucidate determinants of conduction properties in the human heart, we characterized connexin phenotypes of specific human cardiac tissues with different conduction properties.Methods and Results: The distribution and relative abundance of Cx37, Cx40, Cx43, Cx45, and Cx46 were studied immunohistochemically using monospecific antibodies and frozen sections of the sinoatrial node and adjacent atria, the AV node and His bundle, the bundle branches, and the left and right ventricular walls. Patterns of expression of these connexins in the human heart differed from those in previous animal studies. Sinus node gap junctions were small and sparse and contained Cx45 and apparently smaller amounts of Cx40 but no Cx43. AV node gap junctions were also small and contained mainly Cx45 and Cx40 hut, unlike the sinus node, also expressed Cx43. Atrial gap junctions were larger than nodal junctions and contained moderate amounts of Cx40, Cx43, and Cx45. Junctions in the bundle branches were the largest in size and contained abundant amounts of Cx40, Cx43, and Cx45. Gap junctions in ventricular myocardium contained mainly Cx43 and Cx45; only a very small amount of ventricular Cx40 was detected in subendocardial myocyte junctions and endothelial cells of small to medium sized intramural coronary arteries. Minimal Cx37 and Cx46 immunoreactivity was detected between occasional atrial or ventricular myocytes.Conclusions: The relative amounts of individual connexins and the number and size of gap junctions vary greatly in specific regions of the human heart with different conduction properties. These differences likely play a role in regulating cardiac conduction velocity. Differences in the connexin phenotypes of specific regions of the human heart and experimental animal hearts must he considered in future experimental or modeling studies of cardiac conduction.

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00357.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Mesothelioma of AV Node with WPW. This is the first documented case of spontaneous intermittent preexcitation associated with mesothelioma of the atrioventricular (AV) node. A 66‐year‐old male with recurrent atrial arrhythmias, palpitations, heart failure, and marked intra‐atrial conduction defect that required a pacemaker died during sleep. Electrophysiologic study revealed left free‐wall bypass tract with marked intra‐atrial conduction defect and prolonged conduction across the bypass tract. With atrial pacing, high degrees of block were noted in the bypass tract. Serial section of the conduction system and both AV rims revealed two left posterior and lateral bypass pathways with patchy areas of fibrosis. A large mesothelioma (benign AV nodal tumor) almost completely replaced the AV node. In addition, there was marked fatty infiltration of the atria. In summary: (1) the intermittent preexcitation with prolonged conduction across the bypass tract and block with atrial pacing were probably related to the incomplete patchy degenerative changes in the bypass tract, and/or almost complete replacement of the AV node by the tumor; (2) the intra‐atrial conduction defect was probably related to the replacement of the AV node by mesothelioma and/or the fatty infiltration of the atria: and (3) the paroxysmal atrial arrhythmias probably reflect the marked atria

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00358.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Stored Electrograms. Implantable defibrillators have evolved from simple event counters to sophisticated diagnostic monitoring units capable of storing electrocardiographic information surrounding arrhythmia events and device therapy. In this review, the nature and characteristics of these stored electrocardiographic recordings are discussed and examples displayed. Potential benefits and limitation of stored electrogram analysis are described with respect to both clinical utility and the ability to enhance our understanding of ventricular arrhythmogenesis. Finally, future developments to improve data storage, retrieval, and analysis are identified.

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00359.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Catheter Ablation. Application of radiofrequency energy to arrhythmogenic substrates after careful cardiac mapping could ensure a high success rate in eliminating certain types of tachyarrhythmias. Future studies of catheter ablation will focus on how to improve ablation efficacy and achieve a better result in various types of tachyarrhythmias. More information about the arrhythmogenic mechanisms will be provided to improve the knowledge of diagnostic and interventional electrophysiology.

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00360.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00361.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00362.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Cardiac Arrhythmia Therapy. The purpose of this review is to consider our understanding of the mechanisms of action of cardiac antiarrhythmic drugs, as well as the status of our comprehension of arrhythmias and their therapy. The approach will be to review the basis for normal electrical activity of the heart, the mechanisms for cardiac arrhythmias, and our understanding of the mechanisms of drug action, and to distill from these strategies for the future. Immediate strategies in the prevention and treatment of life‐threatening arrhythmias will most likely continue to make use of catheter and electrically based therapy, but the longterm treatment of large populations of individuals will still require the search for, and testing and administration of, pharmacologic therapy. It is emphasized that simplistic approaches to the solution of the complex problem of arrhythmias and their management will probably continue to cause problems, and that only by mastering the complexities of pathophysiology may success be best assure

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1995.tb00363.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY