QT corrected for heart rate and relation between QT and RR intervals in beagle dogs

Matsunaga, Toshiyuki; Mitsui, Toshio; Harada, Tsuyoshi; Inokuma, Masanori; Murano, Hiroyuki; Shibutani, Yasunori

doi:10.1016/s1056-8719(97)00098-1

Cited by 80 publications

(59 citation statements)

References 26 publications

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“…Another advantage of the QTcV formula is its simplicity in comparison with other proposals involving logarithmic (Matsunaga et al 1997), covariance (Spence et al 1998), exponential (Raunig et al 2001), or linear (Davey 2002, King et al 2006, Ollerstam et al 2007, Sivarajah et al 2010 analysis. These alternative methods are extremely valuable in toxicological studies since they are very reliable and yield QTc values that are not significantly influenced by HR.…”

Section: Discussionmentioning

confidence: 99%

QT interval in healthy dogs: which method of correcting the QT interval in dogs is appropriate for use in small animal clinics?

Oliveira

Muzzi

et al. 2014

Pesq. Vet. Bras.

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Pesq. Vet. Bras. 34(5):469-472, maio 2014 469 RESUMO.-[Intervalo QT em cães hígidos: qual método de correção para o intervalo QT é mais apropriado na clínica de pequenos animais?] O intervalo QT do eletrocardiograma (ECG) é influenciado por variações da frequência cardíaca (FC), o que pode levar a erros na interpretação de sua duração. Considerando que as alterações na duração do intervalo QT refletem anormalidades da repolarização ventricular, as quais predispõem a ocorrência de arritmias, esta variável deve ser devidamente avaliada. O objetivo deste trabalho foi determinar qual método de correção do intervalo QT é mais adequado para os cães, considerando-se diferentes intervalos de FC normais. Cães adultos saudáveis, de diferentes raças (n=130; Pastor Alemão, Boxer, Pit Bull Terrier e Poodle) foram submetidos ao exame eletrocardiográfico, no qual se determinaram os intervalos QT a partir da derivação bipolar II e foram corrigidos os efeitos da FC por meio da aplicação de três fórmulas, envolvendo regressão quadrática, cúbica ou linear. Os valores do QT corrigido (QTc) obtidos utilizando as diversas fór-mulas foram significativamente diferentes (ρ<0,05), sendo os derivados da equação QTcV = QT + 0,087 (1-RR), os mais consistentes (regressão linear). The electrocardiography (ECG) QT interval is influenced by fluctuations in heart rate (HR) what may lead to misinterpretation of its length. Considering that alterations in QT interval length reflect abnormalities of the ventricular repolarisation which predispose to occurrence of arrhythmias, this variable must be properly evaluated. The aim of this work is to determine which method of correcting the QT interval is the most appropriate for dogs regarding different ranges of normal HR (different breeds). Healthy adult dogs (n=130; German Shepherd, Boxer, Pit Bull Terrier, and Poodle) were submitted to ECG examination and QT intervals were determined in triplicates from the bipolar limb II lead and corrected for the effects of HR through the application of three published formulae involving quadratic, cubic or linear regression. The mean corrected QT values (QTc) obtained using the diverse formulae were significantly different (ρ<0.05), while those derived according to the equation QTcV = QT + 0.087(1-RR) were the most consistent (linear regression). QTcV values were strongly correlated (r=0.83) with the QT interval and showed a coefficient of variation of 8.37% and a 95% confidence interval of 0.22-0.23 s. Owing to its simplicity and reliability, the QTcV was considered the most appropriate to be used for the correction of QT interval in dogs. intervalo de confiança de 95% de 0,22-0,23s. Devido à confiabilidade dos dados, o QTcV foi considerado o mais apropriado para ser utilizado para a correção do intervalo QT em cães, além de ser um método de fácil execução.

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Section: Discussionmentioning

confidence: 99%

QT interval in healthy dogs: which method of correcting the QT interval in dogs is appropriate for use in small animal clinics?

Oliveira

Muzzi

et al. 2014

Pesq. Vet. Bras.

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“…Since a change in HR affects QT interval, coincident changes in HR should be taken into account when interpreting in vivo data. Although the most common approach to this problem is to use conventional correction formulae, such as Fridericia or other singlecoefficient models, these models may not be sufficient to describe the QT-RR relationship in conscious dogs and may produce overestimation at short RR intervals (44,45). Therefore, it is likely that nifedipine resulted in a false-positive indication of QTcF prolongation, since the change was accompanied by a marked increase in HR.…”

Section: Effect Of a Change In Heart Rate On The Qtc Intervalmentioning

confidence: 99%

QT PRODACT: In Vivo QT Assay in the Conscious Dog for Assessing the Potential for QT Interval Prolongation by Human Pharmaceuticals

et al. 2005

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Abstract. The goal of the present study was to examine the utility of the conscious dog model by assessing the QT-interval-prolonging potential of ten positive compounds that have been reported to induce QT interval prolongation in clinical use and seven negative compounds considered not to have such an effect. Three doses of test compounds or vehicle were administered orally to male beagle dogs (n = 4), and telemetry signals were recorded for 24 h after administration. All positive compounds (astemizole, bepridil, cisapride, E-4031, haloperidol, MK-499, pimozide, quinidine, terfenadine, and thioridazine) caused a significant increase in the corrected QT (QTc) interval, with a greater than 10% increase achieved at high doses. In contrast, administration of negative compounds (amoxicillin, captopril, ciprofloxacin, diphenhydramine, nifedipine, propranolol, and verapamil) did not produce any significant change in the QTc interval, with the exception of nifedipine that may have produced an overcorrection of the QTc interval due to increased heart rate. The estimated plasma concentrations of the positive compounds that caused a 10% increase in the QTc interval were in good agreement with the plasma / serum concentrations achieved in humans who developed prolonged QT interval or torsade de pointes (TdP). Although careful consideration should be given to the interpretation of QT data with marked heart rate change, these data suggest that an in vivo QT assay using the conscious dog is a useful model for the assessment of QT interval prolongation by human pharmaceuticals. Supplementary material (Appendix): available only at http://dx

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“…The slope of the regression line and the maximum QT interval were increased by treatment with 50 mg/kg of D0870, and the prolongation rates of the latter were estimated to be 62-105% by F6. The increase in the slope of the regression line could be indicated even by the other formulas (F1 to F5), whereas the maximum QT interval could not be described by these formulas [21]. After having been fit to Kovács formula, the QT-RR pairs were indicated as two lines with different slope, and reverse use-dependency became clear both graphically ( Fig.…”

Section: Analysis Of the Relationship Between Qt And Rr Intervalsmentioning

confidence: 93%

“…The relation between QT and preceding RR intervals was assessed by using the data obtained from ambulatory electrocardiograms that had been recorded continuously for 24 hr before and 24 hr after the treatment with the loading dose, 50 mg/kg, of D0870 [19]. The analysis was performed according to the procedures described previously [21]. Briefly, a total number of 100 to 150 points of QT-RR pairs per animal was collected from before and 3 to 24 hr after treatment with 50 mg/kg of D0870, because the plasma concentrations of the compound and the QT intervals were maintained at almost constant values during that period.…”

Section: ) Animalsmentioning

confidence: 99%

“…The regression parameters, a and b, of Kovàcs formula represent the slope of the regression line and the maximum QT interval with an increase in RR interval, respectively [21]. The slope of the regression line and the maximum QT interval were increased by treatment with 50 mg/kg of D0870, and the prolongation rates of the latter were estimated to be 62-105% by F6.…”

Section: Analysis Of the Relationship Between Qt And Rr Intervalsmentioning

confidence: 99%

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D0870, an Antifungal Agent, Induces Reverse Use-dependent QQT Prolongation in Dogs.

Matsunaga

Harada

Hirata

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. We previously reported that D0870 induced QT prolongation and sudden death due to torsades de pointes (TdP) in dogs and that catecholamines played an important part in the development of the sudden death. In the present study, we analyzed in detail the ambulatory electrocardiographic recordings obtained from the just-mentioned study to elucidate the mechanism of the onset of TdPs and conducted an in vitro study using isolated canine Purkinje fibers to assess the effect of D0870 on repolarization. The hearts with TdPs observed before the sudden death showed a higher sinus rate for 5 and 10 sec before the onset, a shorter coupling interval, and a higher ventricular tachycardia rate compared with those having the non-sustained TdPs. These findings suggest that D0870-induced fatal TdPs may be provoked by a triggered activity developed from delayed after depolarizations. In contrast, as the pause-dependent, non-sustained TdPs in bradycardia showed a typical "short-long-short" sequence, they may be developed from early afterdepolarization . Moreover, the results of the in vitro study supported our contention that D0870 induced QT prolongation in a reverse use-dependent manner in vivo and suggested that it may inhibit not only rapidly activating delayed rectifier potassium current (Ik r ) but also L-type Ca current (I Ca-L ).-KEY WORDS: antifungal agent, canine, D0870, QT prolongation, TdP. D0870, which is chemically (R)-(, is a new antifungal agent that is active orally and parenterally against a wide range of systemic mycosis, even in the immunocompromised models [31]. We previously reported that D0870 induced plasma concentrationdependent QT prolongation and sudden death due to ventricular fibrillation (VF) associated with torsades de pointes (TdP) in a dog study using loading (50 mg/kg) and maintenance (5 mg/kg/day) doses with long-term ambulatory electrocardiographic monitoring [19]. A previous study revealed that D0870 induced three different types of Tdp, namely, the rate-dependent and pausedependent non-sustained TdP (r-nsTdP and p-nsTdP, respectively), and the rate-dependent sustained TdP (rsTdP). Then, we demonstrated the secondary role of catecholamines in the onset of sudden death induced by D0870 [20]. In the present study, to evaluate the characteristics of QT prolongation induced by D0870, we compared the QT-RR relations between before and after the treatment with D0870 by fitting to 2-parameter QT p r e d i c t i o n f o r m u l a s t h e d a t a o f a m b u l a t o r y electrocardiograms obtained from the dogs used in a previous study [19]. Also, to clarify the characteristics of the TdPs observed before the sudden death induced by D0870, we performed a greater detailed analysis of the above-mentioned electrocardiograms. In addition, we examined the transmembrane action potential of isolated canine Purkinje fibers to assess the effect of D0870 on repolarization. MATERIALS AND METHODS 1) Test materialsAn injectable preparation containing 50 mg of D0870 per 20 ml of a sterile lipid emulsion, su...

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QT corrected for heart rate and relation between QT and RR intervals in beagle dogs

Cited by 80 publications

References 26 publications

QT interval in healthy dogs: which method of correcting the QT interval in dogs is appropriate for use in small animal clinics?

QT interval in healthy dogs: which method of correcting the QT interval in dogs is appropriate for use in small animal clinics?

QT PRODACT: In Vivo QT Assay in the Conscious Dog for Assessing the Potential for QT Interval Prolongation by Human Pharmaceuticals

D0870, an Antifungal Agent, Induces Reverse Use-dependent QQT Prolongation in Dogs.

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