Correlation between Effects of Ouabain on the Canine Electrocardiogram and Transmembrane Potentials of Isolated Purkinje Fibers

Rosen, Michael R.; Gelband, Henry; Hoffman, Brian F.

doi:10.1161/01.cir.47.1.65

Cited by 159 publications

(43 citation statements)

References 21 publications

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“…The characteristics (e.g., rate dependence) of the catecholamine-induced afterdepolarizations are similar to those of Purkinje fibers exposed to ouabain (Ferrier et al, 1973;Rosen et al, 1973). Our results show a remarkable similarity between the delayed afterdepolarization in the isolated ventricular myocytes and the ones from multicellular preparations.…”

Section: Discussionsupporting

confidence: 71%

Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Belardinelli¹,

Isenberg²

1983

Circulation Research

181

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SUMMARY. We investigated the effects of adenosine and isoproterenol on enzymatically dispersed ventricular myocytes from bovine and guinea pig hearts. Inrracellular stimulation of relaxed myocytes with regular srriation patterns and normal resting potential resulted in action potentials with full plateaus accompanied by contractions. Adenosine in concentrations up to 0.2 HIM had no significant effect on any of the action potential parameters or on the basal contractility. In contrast, in the same cells, adenosine effectively antagonized the stimulatory effect of isoproterenol. Isoproterenol (1-10 nM) prolonged the action potentials by 34-41%, displaced the plateau to more positive potentials, and caused a 3-fold increase in the extent of myocyte sarcomere shortening. In the presence of adenosine (5-50 HM), isoproterenol increased the action potential duration by only 8-9%, the shift of the plateau was nearly abolished, and the increase in the extent of myocyte sarcomere shortening was less than 10%. In some of the myocytes, isoproterenol (1-10 nM) induced depolarizing afterpotentials accompanied by aftercontractions. The afterdepolarizations occasionally reached threshold resulting in triggered sustained rhythmic activity. Adenosine (20-50 HM) not only reduced the amplitude of the afterdepolarizarions and aftercontractions, but also abolished the sustained rhythmic activity. We conclude, first, that isolated ventricular myocytes respond to isoproterenol and adenosine; second, that adenosine has no direct effect, but effectively antagonizes the stimulatory actions of isoproterenol; third, that findings are consistent with the ones reported for multicellular ventricular preparations; fourth, that adenosine concentrations required to attenuate the actions of isoproterenol are in the range of adenosine concentrations released by cardiac cells when oxygen availability is limited and/or demand is increased; and fifth, that endogenously released adenosine may modulate the electrophysiological and contractile effects of catecholamines. (Circ Res 53: 287-297, 1983) RECENTLY, adenosine has been recognized to antagonize specifically the inotropic, and some of the electrophysiological and metabolic, effects of catecholamines in ventricular myocardium (Schrader et al., 1977;Dobson, 1978;Baumann et al., 1981, Belardinelli et al., 1982.The observation that adenosine antagonizes the inotropic effect of tyTamine, but not the tyramineinduced release of norepinephrine, has been assumed to indicate that adenosine acts postsynaptically (Schrader et al., 1979). However, adenosine has also been shown to inhibit the stimulationinduced release of norepinephrine from sympathetic nerve terminals in the heart (Hedquist and Fredholm, 1976;Wakade and Wakade, 1978). Consistent with this latter finding, in the dog, adenosine has been shown to reduce the increase in heart rate induced by electric stimulation of the right stellate ganglion (Horn and Lokhandwala, 1981). These observations suggest that the antagonism between adenosine and sympa...

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Section: Discussionsupporting

confidence: 71%

Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Belardinelli¹,

Isenberg²

1983

Circulation Research

181

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“…The delayed afterdepolarizations and triggered activity observed in our study were similar to those noted in other preparations. 8 [23][24][25][26][27] The amplitude and coupling interval of delayed afterdepolarizations were a function of the cycle length and number of preceding impulses, and were dependent on extracellular Ca' + concentration (figures 5 to 7).…”

Section: Discussionmentioning

confidence: 99%

Automaticity, triggered activity, and responses to adrenergic stimulation in cat subendocardial Purkinje fibers after healing of myocardial infarction.

Kimura¹,

Bassett²,

Kohya³

et al. 1987

Circulation

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We studied automaticity, triggered activity, and responses to a-and /8-adrenergic stimulation in subendocardial Purkinje fibers overlying healed infarct scars (infarct preparation) and from remote normal zones (noninfarct preparation) of cat left ventricles. The preparations were studied 2 to 4 months after ligation of multiple distal tributaries of the left anterior descending and circumflex arteries. Subendocardial Purkinje fibers from corresponding areas of normal hearts served as control samples (control preparation). Transmembrane action potential characteristics and rates of automaticity (spontaneous phase 4 depolarization) did not differ among control, noninfarct, and infarct preparations. However, overdrive at cycle lengths of less than 400 msec suppressed automaticity to a greater degree in Purkinje fibers of infarct preparations than those of control and noninfarct preparations. Changes in automatic rate during superfusion with isoproterenol (10-'M to 10 -6M) were not different among the three groups of preparations, but exposure to phenylephrine (10-9M to 10 -5M) in the presence of 5 X 10-7M propranolol reduced the automatic rate to a greater degree in Purkinje fibers of infarct preparations than those of control or noninfarct preparations. Triggered activity arising from delayed afterdepolarizations was recorded in 10 of 29 infarct preparations (34%), but not in 12 control and 10 noninfarct preparations. These afterpotentials were augmented by increasing extracellular Ca+ + concentration, 10 -7M isoproterenol, and 10 -5M phenylephrine in the presence of 5 x 10 -7M propranolol. We conclude that Purkinje fibers overlying healed infarct scars have altered physiology of spontaneous automaticity, enhanced responses to a-adrenergic interventions, and a tendency to triggered activity, and that both a-and 3-adrenergic effects may result in worsening of arrhythmias by augmentation of afterpotentials in healed myocardial infarction. Circulation 75, No. 3, 651-660, 1987. PREVIOUS studies have suggested that several mechanisms may be responsible for arrhythmias occurring 24 hr after experimental acute myocardial infarction. These include enhanced automaticity of subendocardial Purkinje fibers surviving myocardial infarction,'A triggered activity arising from delayed afterdepolarizations,5 and reentry.6 The infarct zones of canine hearts studied 24 hr after infarction have From the

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“…This diastolic Ca 2ϩ release activates the electrogenic Na ϩ /Ca 2ϩ exchange (NCX), 5 and the resulting inward current can produce a delayed afterdepolarization as well as ectopic pacemaker activity. 6,7 At least 2 factors have been suggested to be involved in producing this diastolic release; (1) an increase of SR Ca 2ϩ content (calcium overload) results in increased frequency of RyR opening until the point that Ca 2ϩ waves are produced. 8 This is thought to be responsible for the arrhythmogenic diastolic Ca 2ϩ release in conditions such as digitalis intoxication 6,7,9 and reperfusion following ischemia; 10 and (2) changes in the properties of the RyR.…”

mentioning

confidence: 99%

“…6,7 At least 2 factors have been suggested to be involved in producing this diastolic release; (1) an increase of SR Ca 2ϩ content (calcium overload) results in increased frequency of RyR opening until the point that Ca 2ϩ waves are produced. 8 This is thought to be responsible for the arrhythmogenic diastolic Ca 2ϩ release in conditions such as digitalis intoxication 6,7,9 and reperfusion following ischemia; 10 and (2) changes in the properties of the RyR. Mutations in the human RyR [11][12][13] or accessory proteins such as calsequestrin 14 increase susceptibility to lethal arrhythmias such as catecholaminergic polymorphic ventricular tachycardia.…”

mentioning

confidence: 99%

Increasing Ryanodine Receptor Open Probability Alone Does Not Produce Arrhythmogenic Calcium Waves

Venetucci

Trafford

Eisner

2007

Circulation Research

176

151

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Abstract-Diastolic waves of Ca 2ϩ release have been shown to activate delayed afterdepolarizations as well as some cardiac arrhythmias. The aim of this study was to investigate whether increasing ryanodine receptor open probability alone or in the presence of ␤-adrenergic stimulation produces diastolic Ca release from the sarcoplasmic reticulum (SR). When voltage-clamped rat ventricular myocytes were exposed to caffeine (0.5 to 1.0 mmol), diastolic Ca 2ϩ release was seen to accompany the first few stimuli but was never observed in the steady state. We attribute the initial phase of diastolic Ca 2ϩ release to a decrease in the threshold SR Ca 2ϩ content required to activate Ca 2ϩ waves and its subsequent disappearance to a decrease of SR content below this threshold. Application of isoproterenol (1 mol

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Correlation between Effects of Ouabain on the Canine Electrocardiogram and Transmembrane Potentials of Isolated Purkinje Fibers

Cited by 159 publications

References 21 publications

Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

Automaticity, triggered activity, and responses to adrenergic stimulation in cat subendocardial Purkinje fibers after healing of myocardial infarction.

Increasing Ryanodine Receptor Open Probability Alone Does Not Produce Arrhythmogenic Calcium Waves

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