Effects of pink grapefruit juice on QT variability in patients with dilated or hypertensive cardiomyopathy and in healthy subjects

Piccirillo, Gianfranco; Magrì, Damiano; Matera, Sabrina; Magnanti, Marzia; Pasquazzi, Eleonora; Schifano, Erika; Velitti, Stefania; Mitra, M; Marigliano, Vincenzo; Paroli, Marino; Ghiselli, Andrea

doi:10.1016/j.trsl.2008.03.002

Cited by 26 publications

(16 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, grapefruit juice has been reported to elicit moderate and marginally noticeable QT prolongation (Figure 8) in normal subjects (Zitron et al ., 2005) which was attributed to the HERG channel inhibitory property of some of its flavonoid ingredients (Scholz et al ., 2005; Zitron et al ., 2005). Pink grapefruit juice ingestion has also been found to increase QT variability index in a small set of patients with dilated and hypertensive cardiomyopathies (Piccirillo et al ., 2008). In addition, it is well known that grapefruit juice strongly inhibits P‐450 which plays an important role of the metabolism of several drugs including those that block cardiac potassium channels and impair repolarization, a mechanism that further contributes to decreased repolarization reserve and enhanced proarrhythmic risk.…”

Section: Clinical Significance Of Reduced Repolarization Reservementioning

confidence: 99%

Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk

Varró

Baczkó

2011

British Journal of Pharmacology

177

179

View full text Add to dashboard Cite

Cardiac repolarization abnormalities can be caused by a wide range of cardiac and non-cardiac compounds and may lead to the development of life-threatening Torsades de Pointes (TdP) ventricular arrhythmias. Drug-induced Torsades de Pointes is associated with unexpected and unexplained sudden cardiac deaths resulting in the withdrawal of several compounds in the past. To better understand the mechanism of such unexpected sudden cardiac deaths, the concept of repolarization reserve has recently emerged. According to this concept, pharmacological, congenital or acquired impairment of one type of transmembrane ion channel does not necessarily result in excessive repolarization changes because other repolarizing currents can take over and compensate. In this review, the major factors contributing to repolarization reserve are discussed in the context of their clinical significance in physiological and pathophysiological conditions including drug administration, genetic defects, heart failure, diabetes mellitus, gender, renal failure, hypokalaemia, hypothyroidism and athletes' sudden deaths. In addition, pharmacological support of repolarization reserve as a possible therapeutic option is discussed. Some methods for the quantitative estimation of repolarization reserve are also recommended. It is concluded that repolarization reserve should be considered by safety pharmacologists to better understand, predict and prevent previously unexplained drug-induced sudden cardiac deaths. AbbreviationsAPD, action potential duration; ATP, adenosine triphosphate; ATX II, Anemonia sulcata toxin; cAMP, 3′-5′-cyclic adenosine monophosphate; DAD, delayed afterdepolarization; EAD, early afterdepolarization; ERP, effective refractory period; ICa,L, L-type inward calcium current; IKr, rapid delayed rectifier potassium current; IKs, slow delayed rectifier potassium current; INa, inward sodium current; Ito, transient outward potassium current; LQT1, long QT syndrome 1; LQT2, long QT syndrome 2; LQT3, long QT syndrome 3; LQT7, long QT syndrome 7; LQTS, long QT syndromes; miRNA, micro ribonucleic acid; NCX, Na + -Ca 2+ exchanger; PKA, protein kinase A; PKC, protein kinase C; TdP, Torsades de Pointes IntroductionIt is well known that certain antiarrhythmic drugs induce life-threatening Torsades de Pointes (TdP) arrhythmia in 3-5% of patients. This was not considered particularly surprising because the drugs in question were expected to affect cardiac transmembrane ion channels and the electrophysiological properties of the heart as part of their therapeutic effect. Recently, however, there has been increasing concern about TdP arrhythmia and sudden death caused by noncardiac drugs. The incidence of TdP induced by non-cardiac drugs is usually low (less than 1:10 000 or 1:100 000). BJPBritish Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2011 14 British Journal of Pharmacology (2011) However, several of them including astemizole, cisapride, grepafloxacin, terfenadine, terolidine have been withdrawn from the market due to the...

show abstract

Section: Clinical Significance Of Reduced Repolarization Reservementioning

confidence: 99%

Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk

Varró

Baczkó

2011

British Journal of Pharmacology

177

179

View full text Add to dashboard Cite

show abstract

“…Their computer processing facilitates a number of ECG measurements that were previously unobtainable. Among such measurements, beat-to-beat QT interval variability has attracted some popularity and has been investigated in a variety of physiological and clinical conditions (3,9,11,(15)(16)(17)21). Different numerical quantifiers of the beat-to-beat QT variability have been proposed, but perhaps most frequently the so-called QT variability index (QTVI) has been used.…”

Section: Division Of Cardiac and Vascular Sciences St George's Unimentioning

confidence: 99%

Beat-to-beat QT variability and cardiac autonomic regulation

Malik¹

2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…1,2 Thus, spatial 12,13 and temporal 14,15 myocardial repolarization dispersion are both influenced by several structural changes in the ventricular myocardium, as well as by autonomic cardiovascular control and many other factors including age, 15,16 and medications. [17][18][19] Even in healthy subjects, the duration of myocardial repolarization, is inherently nonhomogeneous given that the action potential has a shorter duration in epicardial than in M-cell layers. 20,21 Some investigators suggest that the Q-T peak interval on the surface electrocardiogram (ECG) ( Fig.…”

mentioning

confidence: 99%

Indexes of Temporal Myocardial Repolarization Dispersion and Sudden Cardiac Death in Heart Failure: Any Difference?

Piccirillo

Rossi

Mitra

et al. 2012

Noninvasive Electrocardiol

Self Cite

View full text Add to dashboard Cite

show abstract

Effects of pink grapefruit juice on QT variability in patients with dilated or hypertensive cardiomyopathy and in healthy subjects

Cited by 26 publications

References 29 publications

Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk

Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk

Beat-to-beat QT variability and cardiac autonomic regulation

Indexes of Temporal Myocardial Repolarization Dispersion and Sudden Cardiac Death in Heart Failure: Any Difference?

Contact Info

Product

Resources

About