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Obesity Potentiates the Risk of Drug-Induced Long QT Syndrome - Preliminary Evidence from WNIN/Ob Spontaneously Obese Rat

Abstract

Drug-induced long QT syndrome (DI-LQTS) is fatal and known to have a higher incidence in women rather than in men. Multiple risk factors potentiate the incidence of DI-LQTS, but the actual contribution of obesity remains largely unexplored. Correspondingly, the present study is aimed to evaluate the susceptibility of DI-LQTS in WNIN/Ob rat in comparison with its lean counterpart using 3-lead electrocardiography. Four- and eight-month-old female WNIN/Ob and their lean controls were used for the experimentation. Non-invasive blood pressure measurement and total body electric conductivity (TOBEC) analysis were carried out. After the baseline evaluations, animals were anesthetized with Ketamine (50 mg/kg). Haloperidol (12.5 mg/kg single dose) was administered intraperitoneally and ECG was taken at 0, 10, 20, 30, 60 min, and 24 h time points. Myocardial lystes were used to assess the BNP, protein carbonylation, and hydroxyproline content. Adiposity, as assessed by TOBEC, is higher in obese rats with elevated mean arterial blood pressure. Baseline-corrected QT interval (QTc) is significantly higher in the obese rat with a wider QRS complex. The incidence of PVC and VT are more intense in the obese rat. Haloperidol-induced QT prolongation in obese rats was rapidly induced than in lean, which was observed to remain till 24 h in obese groups while normalized in lean controls. Higher levels of BNP, protein carbonylation, hydroxyproline content, and relative heart weights indicated the presence of cardiac hypertrophy. The study provides preliminary evidence that obesity can be a potential risk factor for DI-LQTS with faster onset and longer subsistence.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to acknowledge Indian Council for Medical Research, New Delhi, India for financially funding this work [Grant No: 3/1/3/PDF (18)/2018-HRD]. We thank Director, ICMR—NARFBR, Director, ICMR- NIN, and Director NRIUMSD, Hyderabad for their support and facilities.

Funding

The study is funded by Indian Council for Medical Research, [Grant No: 3/1/3/PDF (18)/2018-HRD].

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Authors and Affiliations

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Contributions

Study conception and design: AGP, NHS, PS; Animal breeding husbandry and TOBEC analysis: KPR; Treatment, NIBP, and electrocardiography: AGP, GMH, MHK; Biochemical studies: AGP, KPR, NHS; Statistical analysis: AGP, GMH, MHK, PS.

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Correspondence to Nemani Harishankar.

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The authors declare that they have no conflict of interest.

Ethical Approval

The study is approved by Institutional Animal Ethics Committee [Sanction No: ICMR-NIN/IAEC/02/009/2019].

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Potnuri, A.G., Reddy, K.P., Suresh, P. et al. Obesity Potentiates the Risk of Drug-Induced Long QT Syndrome - Preliminary Evidence from WNIN/Ob Spontaneously Obese Rat. Cardiovasc Toxicol 21, 848–858 (2021). https://doi.org/10.1007/s12012-021-09675-w

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Keywords

  • Drug-induced long QT syndrome
  • Electrocardiography
  • Haloperidol
  • Obesity
  • Risk factor