ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01206.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Unilateral Stellate Block.Introduction:Left sided stellate ganglion predominance has been proposed as a mechanism responsible for lethal ventricular arrhythmias, due to hetaerae nouns ventricular repolarization. To determine the cardiovascular effects of such asymmetric sympathetic ganglion innervations in man, studies were performed in 15 patients undergoing unilateral stellate ganglion blockade for the management of chronic arm pain.Methods and Results:Standard 12‐lead ECGs, systemic blood pressure, body surface potential mapping, and radionuclide angiography were performed during rest and graded exercise before and after blockade. Successful unilateral blockade was accomplished in 13 of the patients, 11 of whom had right‐sided blockade and two left‐sided blockade. No significant changes due to blockade of stellate ganglia, including QT intervals, were detected during rest or graded exercise in standard ECGs. No cardiac rhythm disturbances occurred in these states, Body surface potential maps and arterial blood pressure were similar during resting supine and upright positions, as well as immediately after exercise before and after blockade. Unilateral ganglion blockade did not modify resting or exercise cardiac ejection fractions.Conclusion:Unilateral stellate blockade in man does not induce untoward cardiovascular effects during rest or exe

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01207.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Ischemically‐Injured Myocytes.Introduction:To determine if collagenase‐dispersed epicardial myocytes overlying myocardial infarction reproduce the same altered electrophysiology observed in intact epicardiuma, multicellular tissue preparations and enzymatically‐dispersed myocytes from ischemically‐injured canine subepicardium were examined 1 and 4 days after myocardial infarction.Methods and Results:The electrophysiologica changes observed with alchemic injury in enzymatic ally‐dispersed myocytes were not different from changes observed in multicellular tissue preparations at I and 4 days post infarction. Is chemically‐injured myocytes were depolarized versus normal myocytes at [K0] (2.5 to 40 mM) with reduced membrane potentials also observed in injured subepicardial tissue preparations [K](4 to 24 mM). On day 1, the reduced Vmaxand the prolonged recovery of Vmaxfrom inactivation were consistent with the reduced membrane potentials observed at each [K]+. The half‐maximal Vmax, maximal Vmaxand Boltzmann constant (k) in injured myocytes were unchanged versus normal myocytes. On day 4 postinfarction, the half‐maximal Vmaxwas shifted to a more negative membrane potential, the maximal Vmax. was reduced, and k was increased in injured versus normal myocytes. Prolonged recovery from inactivation was observed with depressed membrane potentials in injured myocytes on day 4.Conclusion:Enzymatically‐dispersed myocytes from ischemically‐injured subepicardium closely reproduce altered cellular properties observed in multicellular tissue preparations. The data suggest that 1 day postinfarction, altered conduction and refractoriness largely result from a reduced membrane potential. At 4 days, a reduced maximal Vmaxa shift in the inactivation curve to more negative voltages, and prolonged recovery of Vmax, from inactivation also contribute to slowed conduction and prolo

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01208.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Effect of Simulated Preconditioning on Neural Response During Ischemia.Introduction:Preconditioning the myocardium with brief episodes of ischemia preserves efferent autonomic responsiveness of noninfarcted myocardium apical to a site of acute transmural ischemia by mechanism(s) still unknown. We hypothesized that repeated brief exposure of the myocardium to a simulated ischemic milieu including hypoxia, high K. low pH, and adenosine would be as effective as brief coronary occlusions in creating this protection.Methods and Results:Open chest anesthetized dogs received an extra corporeal bypass between the left carotid artery and a diagonal branch of the left anterior descending coronary artery. We analyzed the effects of simulated ischemia on the time course and extent of efferent sympathetic denervation during a subsequent 3‐hour sustained ischemia in three groups of dogs: two groups of dogs underwent four cycles of 5‐minute intracoronary perfusion with either hypoxic altered Tyrode's solution (12 mM K+, 6.8 pH, and 10 μ adenosine; n = 11) or normal Tyrode's solution mil. Each Tyrode's perfusion was separated by 5 minutes of blood perfusion prior to permanent coronary occlusion by latex remobilization of the annulated coronary artery. A third group received a continuous 3‐hour blood perfusion before the final ischemic episode (n = 5). Shortening of effective refractory periods (ERPs) induced by bilateral ansae subelaviae stimulation (2 to 4 Hz) basal and apical to the intervention site was determined before and after perfusions and 20, 60, 120, and 180 minutes after sustained occlusion. In all groups, sympathetically‐induced ERP shortening was unchanged at basal sites throughout the experiment. ERP shortening at apical sites was unchanged after perfusions with either the altered or normal Tyrode's solution or after a continuous 3‐hour blood perfusion. However, EKP shortening became significantly attenuated at apical sites after coronary occlusion in all groups. Neither the size in reduction of sympathetically‐induced ERP shortening at apical test sites nor the cumulative percentage of denervated apical test sites (≤ 2‐msec shortening) during a 3‐hour period of permanent ischemia differed significantly among groups (P = 0.052 and P = 0.752, respectively). The degree of subepicardial involvement in the myocardial infarction was comparable among groups.Conclusion:Thus, brief exposure of the left ventricular myocardium to ischemic metabolites prior to a subsequent permanent coronary occlusion does not trigger mechanism(s) that are responsible for protection against efferent sympathetic denervation apical to an area of trans‐mural myocardial

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01209.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Glibenclamide Block of KATPChannels.Introduction:The mechanism by which glibenclamide inhibits KATPchannel activity has been examined in membrane patches from isolated rat ventricular cells.Methods and Results:Inside‐out patches were exposed to zero, or low, [ATP] to activate KATPchannels. Glibenclamide did not affect single channel conductance, but reversibly reduced channel open probability from either side of the membrane. Internal (cytoplasmic) glibenclamide inhibited with half‐maximal inhibitory [glibenclamide] = 6 μM, Hill coefficient = 0.35. Complete channel inhibition was not observed, even at 300μM[glibenclamide]. The response to step increases of internal [glibenclamide]could be resolved into two phases of channel inhibition (t1/2, fast,<1 sec, t1/2, slow= 10.5 ± 0.9 sec, n = 8). Step decrease of [glibenclamide] caused a single resolvable phase of reactivation (t1/2= 20.4 ± 0.7 sec, n = 16). Channel inhibition by internal glibenclamide could be relieved by ADP, but only in the presence of Mg2+.Conclusion:Glibenclamide can inhibit KATPchannels from either side of the membrane, with block from one side being competitive with block from the other. Internal MgADP antagonizes the blocking action of glibenclamide. Glibenclamide inhibition of cardiac KATPchannels differs quantitatively and qualitatively from the inhibition of pancreatic KATPc

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01210.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

EADs and DADs in M Cells.Introduction:Oscillations of membrane potential that attend or follow the cardiac action potential and depend on preceding Tran membrane activity for their manifestation are known as aflerdepolarizations. Early aflerdepolarizations (EADs) interrupt or retard repolarization of the cardiac action potential, whereas delayed afterdepolarizations (DADs) arise after full repolarization. EADs and DADs can give rise to spontaneous action potentials or triggered activity believed to be responsible for a variety of cardiac arrhythmias. Recent studies from our laboratory have highlighted differences in the electrophysiology and pharmacology of three functionally distinct myocardial cell types found in the canine ventricle. Epicardial, M region, and endocardia tissues and cells show distinct, sometimes opposite, responses to a variety of drugs, including those capable of inducing EADs and DADs.Methods and Results:In the present study, we used standard microelectrode techniques to examine the pharmacologic response of these cellular subtypes to therapeutic levels of quinidine and toxic levels of digitalis. Quinidine readily produced prominent EADs and EAD induced triggered activity in tissue preparations from the M region (deep subepicardium), but not in those from epicardium. endocardium, or deep subendocardium of the canine ventricle. Acetylstrophanthidin produced prominent DADs in M cell preparations and subendocardiat Purkinje fibers but only minute DADs, if any, in epicardium, endocardium, or deep subendocardium. DAD‐induced triggered activity was observed to arise only in Purkinje and M cells and never in myocardial tissues from the epicardial, endocardial, or deep subendocardial regions of the ventricular wall.Conclusion:We conclude that EADs, DADs, and triggered activity caused by therapeutic levels of quinidine and toxic levels of digitalis are limited to or much more readily induced in a select population of cells in the deep subepicardial (M cell) region of the canine ventricle in addition to the Purkinje system of the hear

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01211.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01212.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01213.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Cardiovascular K+Channel Molecular Biology. K+channels represent the most diverse class of voltage‐gated ion channels in terms of function and structure. Voltage‐gated K+channels in the heart establish the resting membrane K permeability, modulate the frequency and duration of action potentials, and are targets of several antiarrhythmic drugs. Consequently, an understanding of K+channel structure‐function relationships and pharmacology is of great practical interest. However, the presence of multiple overlapping currents in native cardiac myocytes complicates the study of basic K+channel function and drug‐channel interactions in these cells. The application of molecular cloning technology to cardiovascular K+channels has identified the primary structure of these proteins, and heterologous expression systems have allowed a detailed analysis of channel function and pharmacology without contaminating currents. To date six different K+channels have been cloned from rat and human heart, and all have been functionally characterized in eitherXenopusoocytes or mammalian tissue culture systems. This initial research is an important step toward understanding the molecular basis of the action potential in the heart. An important challenge for the future is to determine the cell‐specific expression and relative contribution of these cloned channels to cardiac exc

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01214.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Sotalol. Sotalol causes noncardioselective beta‐adrenergic antagonism and prolongation of repolarization of cardiac tissues (Class III electrophysiologic action). This dual pharmacologic profile confers unprecedented antiarrhythmic properties to the drug. Sotalol is highly bioavailable when administered orally in the fasting state and is mostly cleared unchanged in the urine with an apparent half‐life of elimination of 15 to 17 hours. It has heen found effective in the suppression of nearly all cardiac arrhythmias, with the exception of those precipitated by prolongation of ventricular repolarization. Its safety and efficacy relative to other antiarrhythmic drugs need to be examined more fully in randomized controlled trials of unselected patients. The adverse effects potentially associated with the use of sotalol are those commonly observed with beta‐adrenergic blockade, as well as those resulting from excessive prolongation of the QT interval. The occurrence of torsade de pointes during treatment with sotalol may be minimized by limiting doses to no more than 640 nig/day and by strictly avoiding the development of hypokalemia. (J Cardiovasc Electrophysiol. Vol. 4, pp. 81–98. Februa

ISSN:1045-3873    

DOI:10.1111/j.1540-8167.1993.tb01215.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY