Non-invasive ECG recording and QT interval correction assessment in anesthetized rats and mice

Botelho, Ana Flávia Machado; Joviano‐Santos, Julliane V.; Santos‐Miranda, Artur; Menezes-Filho, José Evaldo Rodrigues de; Soto-Blanco, Benito; Cruz, Jáder Santos; Guatimosim, Cristina; Melo, Marília Martins

doi:10.1590/1678-6160-pvb-6029

Cited by 11 publications

(6 citation statements)

References 41 publications

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“…The purpose of this study is to determine cardiac changes that occur during and between seizures, and their relationship with repeated seizures. Clinical measurements usually correct for dependence on heart rate, but this process raises problems, which we discuss in subsequent text and assess in our experimental evidence 20,21 . Following a single injection of TeNT into the hippocampus in rats, we record electrocorticogram (ECoG), ECG, and seizure‐related behaviors in freely moving animals continuously for periods of weeks.…”

Section: Introductionmentioning

confidence: 99%

Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval

2020

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Objective: To determine electrical changes in the heart in a chronic, nonstatus model of epilepsy. Methods: Electrocorticography (ECoG) and electrocardiography (ECG) of nine animals (five made epileptic by intrahippocampal injection of tetanus neurotoxin (TeNT) and four controls), are monitored continuously by radiotelemetry for up to 7 weeks. Results: Epileptic animals develop a median of 168 seizures, with postictal tachycardias reaching a mean of 487 beats/min and lasting a mean of 661 seconds. Ictal changes in heart rate include tachycardia and in the case of convulsive seizures, bradyarrhythmias resembling Mobitz type 1 second-degree atrioventricular block; notably the P-R interval increased before block. Postictally, the amplitude of T wave increases. Interictally, QT dependence on RR is modest and conventional QT corrections prove ineffective. Interictal QT intervals, measured at a heart rate of 400 bpm, increased from 65 to 75 ms, an increase dependent on seizure incidence over the preceding 10-14 days. Significance: Repeated seizures induce a sustained tachycardia and increase in QT interval of the ECG and evoke arrhythmias including periods of atrioventricular block during Racine type 4 and 5 seizures. These changes in cardiac function may predispose to development in fatal arrhythmias and sudden death in humans with epilepsy. K E Y W O R D S cardiac dysfunction, epilepsy, QT correction, QT prolongation | 799 JEFFERYS Et al. |

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Section: Introductionmentioning

confidence: 99%

Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval

2020

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“…In fact, none of the parameters recorded exhibited significant alterations after concluding the total observation period of 48 h, pointing to healthy profiles for all the experimental groups (Supplementary Tables S1 and S2). Also, the cardiological monitoring of the animals and therefore, any change noticed in their ECG waves and intervals is particularly important in this kind of toxicological studies (Botelho et al ., 2019). Certainly, such alterations were not recorded after the administration of these derivatives, either p.o.…”

Section: Discussionmentioning

confidence: 99%

Activity profile of two 5-nitroindazole derivatives over the moderately drug-resistant Trypanosoma cruzi Y strain (DTU TcII): in vitro and in vivo studies

Fonseca-Berzal¹,

Silva²,

Batista³

et al. 2020

Parasitology

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In previous studies, we have identified several families of 5-nitroindazole derivatives as promising antichagasic prototypes. Among them, 1-(2-aminoethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one, (hydrochloride) and 1-(2-acetoxyethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one (compounds 16 and 24, respectively) have recently shown outstanding activity in vitro over the drug-sensitive Trypanosoma cruzi CL strain (DTU TcVI). Here, we explored the activity of these derivatives against the moderately drug-resistant Y strain (DTU TcII), in vitro and in vivo. The outcomes confirmed their activity over replicative forms, showing IC50 values of 0.49 (16) and 5.75 μm (24) towards epimastigotes, 0.41 (16) and 1.17 μm (24) against intracellular amastigotes. These results, supported by the lack of toxicity on cardiac cells, led to better selectivities than benznidazole (BZ). Otherwise, they were not as active as BZ in vitro against the non-replicative form of the parasite, i.e. bloodstream trypomastigotes. In vivo, acute toxicity assays revealed the absence of toxic events when administered to mice. Moreover, different therapeutic schemes pointed to their capability for decreasing the parasitaemia of T. cruzi Y acute infected mice, reaching up to 60% of reduction at the peak day as monotherapy (16), 79.24 and 91.11% when 16 and 24 were co-administered with BZ. These combined therapies had also a positive impact over the mortality, yielding survivals of 83.33 and 66.67%, respectively, while untreated animals reached a cumulative mortality of 100%. These findings confirm the 5-nitroindazole scaffold as a putative prototype for developing novel drugs potentially applicable to the treatment of Chagas disease and introduce their suitability to act in combination with the reference drug.

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“…For each session, we calculated the following ECG parameters: P-wave duration, QRS, RR, PR, JT, and QT intervals. To compensate for the elevated mouse heart rate, we corrected the QT interval (QTc) with Hodges’ formula (the most effective for rodents, [ 84 ]).…”

Section: Methodsmentioning

confidence: 99%

Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder

Loi

Bastianini

Candini

et al. 2023

IJMS

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CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe neurodevelopmental disease that mostly affects girls, who are heterozygous for mutations in the X-linked CDKL5 gene. Mutations in the CDKL5 gene lead to a lack of CDKL5 protein expression or function and cause numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, gastrointestinal problems, and severe neurodevelopmental impairment. Mouse models of CDD recapitulate several aspects of CDD symptomology, including cognitive impairments, motor deficits, and autistic-like features, and have been useful to dissect the role of CDKL5 in brain development and function. However, our current knowledge of the function of CDKL5 in other organs/tissues besides the brain is still quite limited, reducing the possibility of broad-spectrum interventions. Here, for the first time, we report the presence of cardiac function/structure alterations in heterozygous Cdkl5 +/− female mice. We found a prolonged QT interval (corrected for the heart rate, QTc) and increased heart rate in Cdkl5 +/− mice. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Interestingly, Cdkl5 +/− hearts showed increased fibrosis, altered gap junction organization and connexin-43 expression, mitochondrial dysfunction, and increased ROS production. Together, these findings not only contribute to our understanding of the role of CDKL5 in heart structure/function but also document a novel preclinical phenotype for future therapeutic investigation.

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Non-invasive ECG recording and QT interval correction assessment in anesthetized rats and mice

Cited by 11 publications

References 41 publications

Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval

Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval

Activity profile of two 5-nitroindazole derivatives over the moderately drug-resistant Trypanosoma cruzi Y strain (DTU TcII): in vitro and in vivo studies

Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder

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