Antipsychotic Haloperidol as a Ligand of Sigma Receptors and its Cardiotoxicity

CHOVANEC, Peter, Drahomír HORKÝ a Marie NOVÁKOVÁ. Antipsychotic Haloperidol as a Ligand of Sigma Receptors and its Cardiotoxicity. In Morphology 2007. 1. vyd. Bratislava: Slovak Anatomical Society, Slovak Medical Society, 2007, s. 46-47, 1 s. ISBN 978-80-89305-01-8.

Základní údaje

Originální název

Antipsychotic Haloperidol as a Ligand of Sigma Receptors and its Cardiotoxicity

Název česky

Antipsychotikum Haloperidol jako ligand sigma receptorů a jeho kardiotoxicita

Autoři

CHOVANEC, Peter, Drahomír HORKÝ a Marie NOVÁKOVÁ

Vydání

1. vyd. Bratislava, Morphology 2007, od s. 46-47, 1 s. 2007

Nakladatel

Slovak Anatomical Society, Slovak Medical Society

---

Další údaje

Typ výsledku

Stať ve sborníku

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Lékařská fakulta

ISBN

978-80-89305-01-8

Klíčová slova anglicky

sigma receptor;haloperidol;myocardium;cardiotoxicity;rat;guinea pig

Štítky

cardiotoxicity, guinea pig, haloperidol, myocardium, rat, sigma receptor

Příznaky

Mezinárodní význam, Recenzováno

---

Anotace

V originále

The Sigma receptors were indentified in many tissues include a cardiac tissue. At first they were members of opioid receptors family. Later they were reclassified, due to their ability to bind ligands of nonopioid character. The point of this study was to investigate submicroscopic and physiologic changes of cardiomyocytes, throughout acute effect of haloperidol (H). For this study we chose two rats and two guinea pigs. One of each group as a control (C) and one as an experimental (E) animal. The animals were of male sex, because it is highly possible, that the endogenous ligand of sigma receptors is progesterone. It could interfere with H, and therefore induce false positivity. The animals were sacrificed by cervical dislocation in ether narcosis. We put out their hearts immediately and put them into the Langendorff apparatus. Simultaneously we scaned an elektrocardiogram (ECG). At first each heart was perfused by Krebs-Henseleit solution (KHS) for 30 minutes, then washed the C by KHS , the E by H at the concentration of 10 nM for 30 minutes. Afterwards we washed out the hearts by KHS. Finaly was perfused by 3% solution of glutaraldehyde for 10 minutes. The hearts were cut in strips 1x1x3 mm from both atria and both ventricles. Cardiac tissue was processed for electron microscopy by standard procedure. The electronmicrographs showed, that the ultrastructure of C was normal. In E, there were damages of Z discs. The mitochondria were elongated, many of them were swollen and rounded. We can not leave out of consideration the agglomeration of mitochondria. We observed the increased amount of mitochondrial corpuscles. The diads were widened. ECG results in C accounted no pathology. In E, we could see alterations immediately after the perfusion of H. The QT interval was elongated followed by retarding of the heart rate. Then the ventricular arrythmias were discovered, both the free and the fixed arrythmias. Analogous to other studies H is considered to be toxic, too. The reason of ECG pathology is perhaps caused by the activity of H at kalium channels. But some changes we can not explain this way. It is possible, that the dilatation of diads and anomalies at mitochondria manipulate the calcium (Ca2+) homeostasis. This homeostasis is important in heart action, too.

Česky

The Sigma receptors were indentified in many tissues include a cardiac tissue. At first they were members of opioid receptors family. Later they were reclassified, due to their ability to bind ligands of nonopioid character. The point of this study was to investigate submicroscopic and physiologic changes of cardiomyocytes, throughout acute effect of haloperidol (H). For this study we chose two rats and two guinea pigs. One of each group as a control (C) and one as an experimental (E) animal. The animals were of male sex, because it is highly possible, that the endogenous ligand of sigma receptors is progesterone. It could interfere with H, and therefore induce false positivity. The animals were sacrificed by cervical dislocation in ether narcosis. We put out their hearts immediately and put them into the Langendorff apparatus. Simultaneously we scaned an elektrocardiogram (ECG). At first each heart was perfused by Krebs-Henseleit solution (KHS) for 30 minutes, then washed the C by KHS , the E by H at the concentration of 10 nM for 30 minutes. Afterwards we washed out the hearts by KHS. Finaly was perfused by 3% solution of glutaraldehyde for 10 minutes. The hearts were cut in strips 1x1x3 mm from both atria and both ventricles. Cardiac tissue was processed for electron microscopy by standard procedure. The electronmicrographs showed, that the ultrastructure of C was normal. In E, there were damages of Z discs. The mitochondria were elongated, many of them were swollen and rounded. We can not leave out of consideration the agglomeration of mitochondria. We observed the increased amount of mitochondrial corpuscles. The diads were widened. ECG results in C accounted no pathology. In E, we could see alterations immediately after the perfusion of H. The QT interval was elongated followed by retarding of the heart rate. Then the ventricular arrythmias were discovered, both the free and the fixed arrythmias. Analogous to other studies H is considered to be toxic, too. The reason of ECG pathology is perhaps caused by the activity of H at kalium channels. But some changes we can not explain this way. It is possible, that the dilatation of diads and anomalies at mitochondria manipulate the calcium (Ca2+) homeostasis. This homeostasis is important in heart action, too.