The long QT syndrome: Effects of drugs and left stellate ganglion block

Milne, John; De, Ward; Spurrell, R. A. J.; Camm, A. John

doi:10.1016/0002-8703(82)90191-0

Cited by 37 publications

(23 citation statements)

References 19 publications

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“…The shortened QTcF interval has a possibility of being falsely noted since the QT interval was not adequately corrected due to the marked decrease in heart rate. It has been reported that dl-propranolol shortened the QTc interval both in humans who had the long QT interval syndrome (34) and in healthy humans (7). In a study with canine Purkinje fibers and ventricular muscles, dl-propranolol at 0.9 µg/ mL shortened APD 50 and APD 90 (35).…”

Section: Discussionmentioning

confidence: 91%

QT PRODACT: Usability of Miniature Pigs in Safety Pharmacology Studies: Assessment for Drug-Induced QT Interval Prolongation

Kano

Toyoshi

Iwasaki³

et al. 2005

J Pharmacol Sci

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Abstract. To investigate whether miniature pigs are useful for evaluating the potential of drugs for drug-induced prolongation of the QT interval, we performed an in vivo QT assay using conscious and unrestricted miniature pigs. Compared with the vehicle average baseline values, haloperidol at 3 and 10 mg / kg, p.o. prolonged the QTcF interval (Fridericia's formula) by 8% -16%. The plasma concentration of haloperidol at which QT interval was prolonged (C max = 42.9 ng / mL) was almost equal to that in humans. dl-Propranolol at 3, 10, and 30 mg / kg, p.o. caused no alterations in QT interval. dl-Propranolol at 3, 10, and 30 mg / kg, at which plasma concentrations were lower than in humans treated with dl-propranolol at the therapeutic dose level, shortened QTcF interval by 7% -12%. dl-Sotalol at 10 mg / kg, p.o. prolonged QTcF interval by 7%. From the above results, we considered that the miniature pig can be used for prediction of drug-induced prolongation of QT interval in humans, and thus, it is one of the useful animal species for assessing electrocardiograms in safety pharmacology studies.

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Section: Discussionmentioning

confidence: 91%

QT PRODACT: Usability of Miniature Pigs in Safety Pharmacology Studies: Assessment for Drug-Induced QT Interval Prolongation

Kano

Toyoshi

Iwasaki³

et al. 2005

J Pharmacol Sci

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“…/3-Blocker therapy has been reported to produce shortening or no change in the QT interval.i8 Recently Milne et al 23 reported that intravenous propranolol produced a differential effect on the QT of patients with the familial vs the idiopathic form of the syndrome when heart rate was kept constant by atrial pacing. In that study two patients with familial syndrome showed QT shortening, whereas QT was unchanged in the other two, who had the idiopathic form of the syndrome.…”

Section: Methodsmentioning

confidence: 99%

Electrophysiologic testing in patients with the long QT syndrome.

Bhandari¹,

Shapiro²,

Morady³

et al. 1985

Circulation

140

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Electrophysiologic studies were performed in 15 patients with syncope and/or cardiac arrest who had the long QT syndrome and 11 control subjects who had normal QT invervals. The syndrome was familial in five patients and idiopathic in 10. All patients had a prolonged QT (546 68 msec, mean ± SD) and corrected QT (550 ± 51 msec). Incremental atrial pacing at cycle lengths of 600 to 400 msec resulted in shortening of the QT interval, but there was no significant difference in the magnitude or percent of shortening of the QT interval between patients with the long QT syndrome and control subjects. Intravenous propranolol did not influence the QT interval measured at fixed atrialpaced cycle lengths in patients with either the familial or idiopathic form of the syndrome. Programmed right and left ventricular stimulation with up to three extrastimuli before and during isoproterenol infusion did not induce sustained ventricular tachycardia or ventricular fibrillation in any of the patients. However, rapid polymorphic nonsustained ventricular tachycardia was induced in six of the 15 patients (40%). Neither the inducibility of nonsustained ventricular tachycardia nor the results of electropharmacologic testing with f-blockers proved to be of any prognostic value during the mean follow-up period of 28 ± 17 months. Electrophysiologic studies are of limited value in the diagnosis and treatment of patients with the long QT syndrome.

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“…Left-sided stellate ganglion blockade may even lead to a shortening of the QT interval [39,40]. Left cardiac sympathetic denervation -LCSD's antifibrillatory effect -has been well described.…”

Section: The Effect Of Regional Anaesthesia Techniques On the Period mentioning

confidence: 99%

“…What also remains important is the impact of baroreceptor stimulation and the effect of hypotension resulting from extensive sympathetic blockade. The adrenergic blockade as a result of spinal or epidural, not including T1-4 fibres, causes severe adrenergic activity above the level of the block and consequently prolongs repolarization [37,38].Left-sided stellate ganglion blockade may even lead to a shortening of the QT interval [39,40]. Left cardiac sympathetic denervation -LCSD's antifibrillatory effect -has been well described.…”

mentioning

confidence: 99%

The influence of regional anaesthesia and local anaesthetics on cardiac repolarization

Biernawska

Kaźmierczak

Kotfis

et al. 2016

Anaesthesiol Intensive Ther

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The normal function of the heart muscle is the result of electro-mechanic and hemodynamic coupling. Modification of the structure and activity of ion channels within the cardiomyocytes may induce cardiac arrhythmias. Electrophysiological mechanisms of arrhythmia, generated by a prolonged period of repolarization, result either from conduction disturbances (reentry mechanism) and/or the induction of beats (early after-depolarizations). Local anaesthetic drug deposition does not affect the repolarization period, as long as the concentration of the free drug in the plasma does not reach the critical value to cause toxic effects in the cardiomyocytes. When analyzing the effect of regional anaesthesia on the repolarization period it is essential to acknowledge the activity or blockade of adrenergic fibres. Blocking the sympathetic fibres' , including level T1 to T4, leads to a shortening of the QT interval and a reduction of QT dispersion. Adrenergic blockade as a result of spinal anaesthesia causes severe adrenergic activity above the level of the block and therefore prolongs repolarization. Stellate ganglion block on the right side causes a significant prolongation of the QT interval and QT dispersion. Regardless of the reasons for prolongation of the repolarization period (congenital or acquired), vigilance is required within the perioperative anaesthetic management of a patient, so as not to lead to the occurrence of ventricular arrhythmias. Regional anaesthesia techniques and properly used local anaesthetic drugs are regarded as being safe in these patients.Key words: long QT syndromes, cardiac repolarization, regional anaesthesia, local anaesthetics Anaesthesiology Intensive Therapy 2016, vol. 48, no 2, 135-141 CARDIAC ELECTROPHYSIOLOGYNormal function of the heart muscle is the result of electro-mechanic and haemodynamic coupling. When considering cardiac electrical activity from the point of view of a working myocardial cell, the following must be acknowledged: the relaxed state (polarization of the cell membrane) and active state (depolarization-repolarization) occurring after activation by the conduction system. Changes in the phases of action potential and the resting potential are the result of a synchronized movement of ionic currents through the ion channels, pumps and cardiomyocyte cell membrane carriers. The period of depolarization is initiated by an inward sodium current (I Na ), supported by an inward calcium current (I Ca-L ). During repolarization the flow of current occurs through the channels conducting the potassium current (I Kr , I Ks , I to , I K (ATP) ) and to a lesser extent by the sodium current (I Na ), calcium current (I Ca-L ) and non-selective cation channel (I NS ). This is depicted in Figure 1.The intracellular influx of calcium ions during the plateau phase enables a calcium dependent calcium release from the sarcoplasmic reticulum, leading to a contraction of the working myocardial cell. Under such physiological conditions during repolarization, potassium I Kr and I Ks...

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The long QT syndrome: Effects of drugs and left stellate ganglion block

Cited by 37 publications

References 19 publications

QT PRODACT: Usability of Miniature Pigs in Safety Pharmacology Studies: Assessment for Drug-Induced QT Interval Prolongation

QT PRODACT: Usability of Miniature Pigs in Safety Pharmacology Studies: Assessment for Drug-Induced QT Interval Prolongation

Electrophysiologic testing in patients with the long QT syndrome.

The influence of regional anaesthesia and local anaesthetics on cardiac repolarization

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