Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP<sub>3</sub> Receptors in Guinea Pig Hearts
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- Stracina Tibor
- Department of Physiology, Faculty of Medicine, Masaryk University
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- Slaninova Iva
- Department of Biology, Faculty of Medicine, Masaryk University
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- Polanska Hana
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University
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- Axmanova Martina
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University
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- Olejnickova Veronika
- Department of Physiology, Faculty of Medicine, Masaryk University
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- Konecny Petr
- Department of Physiotherapy and Rehabilitation, Faculty of Medicine, Masaryk University
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- Masarik Michal
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University
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- Krizanova Olga
- Center for Molecular Medicine, Slovak Academy of Sciences
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- Novakova Marie
- Department of Physiology, Faculty of Medicine, Masaryk University International Clinical Research Center, Animal Center, St. Anne’s Faculty Hospital
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説明
Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.
収録刊行物
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 236 (3), 199-207, 2015
東北ジャーナル刊行会