Acute effects of sigma receptor ligand haloperidol on electrogram and coronary flow in rat isolated heart

NOGOVÁ, Kateřina and Marie NOVÁKOVÁ. Acute effects of sigma receptor ligand haloperidol on electrogram and coronary flow in rat isolated heart. 2008.

Basic information

• Original name: Acute effects of sigma receptor ligand haloperidol on electrogram and coronary flow in rat isolated heart
• Name in Czech: Akutní účinky ligandu sigma receptorů haloperidolu na elektrogram a koronární průtok u isolovaného srdce potkana
• Authors: NOGOVÁ, Kateřina and Marie NOVÁKOVÁ.
• Edition: 2008.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 30105 Physiology
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• Organization unit: Faculty of Medicine
• Keywords in English: rat heart;sigma receptor;haloperidol;arrhythmias
• Tags: arrhythmias, haloperidol, rat heart, sigma receptor
• Tags: International impact

Abstract

Mechanisms of life-threatening cardiovascular side effects of sigma receptor ligands (cardiac arrhythmias such as torsade de pointes, ventricular fibrillation or even cardiac arrest) are not fully elucidated yet. Therefore we examined the effects of their representative haloperidol on 3-D electrogram and mean coronary flow in isolated rat hearts. Eight adult male rats were sacrificed under deep ether anesthesia. The hearts were perfused according to Langendorff with Krebs-Henseleit solution (K-H) at constant pressure (85mmHg) and 37C (CaCl2, 1.2 mM). The experiment consists of four 30min periods: control, 10nM haloperidol, washout, 10nM haloperidol. Ten successive RR intervals were averaged at the end of control (steady state heart rate). This value was used for normalization of heart rate during the rest of experiment. In the same way, QT intervals were examined in order to determine L-QT. The incidence of arrhythmias was assessed according to Lambeth Conventions. Coronary flow was measured every 5th minute. Normalized spontaneous heart rate showed a clear tendency to decrease during both haloperidol applications and this effect was partially reversible. In all hearts, the QT intervals lengthened in the first haloperidol period, partially restored in washout and in the second haloperidol administration QT interval remained unchanged. No significant incidence of life-threatening arrhythmias was observed, except of premature ventricular complexes (occurring as singles, salvos or tachycardia). Three hearts were classified by number 3. The changes of coronary flow were inconsistent and insignificant. In conclusion, QT prolongation observed in our experimental model can explain the occurrence of arrhythmias. No change of QT interval in the second haloperidol application can be reasoned by down-regulation of cardiac sigma receptor.

Abstract (in Czech)

Mechanisms of life-threatening cardiovascular side effects of sigma receptor ligands (cardiac arrhythmias such as torsade de pointes, ventricular fibrillation or even cardiac arrest) are not fully elucidated yet. Therefore we examined the effects of their representative haloperidol on 3-D electrogram and mean coronary flow in isolated rat hearts. Eight adult male rats were sacrificed under deep ether anesthesia. The hearts were perfused according to Langendorff with Krebs-Henseleit solution (K-H) at constant pressure (85mmHg) and 37C (CaCl2, 1.2 mM). The experiment consists of four 30min periods: control, 10nM haloperidol, washout, 10nM haloperidol. Ten successive RR intervals were averaged at the end of control (steady state heart rate). This value was used for normalization of heart rate during the rest of experiment. In the same way, QT intervals were examined in order to determine L-QT. The incidence of arrhythmias was assessed according to Lambeth Conventions. Coronary flow was measured every 5th minute. Normalized spontaneous heart rate showed a clear tendency to decrease during both haloperidol applications and this effect was partially reversible. In all hearts, the QT intervals lengthened in the first haloperidol period, partially restored in washout and in the second haloperidol administration QT interval remained unchanged. No significant incidence of life-threatening arrhythmias was observed, except of premature ventricular complexes (occurring as singles, salvos or tachycardia). Three hearts were classified by number 3. The changes of coronary flow were inconsistent and insignificant. In conclusion, QT prolongation observed in our experimental model can explain the occurrence of arrhythmias. No change of QT interval in the second haloperidol application can be reasoned by down-regulation of cardiac sigma receptor.

Links

• GA102/07/1473, research and development project: Name: Optické metody registrace elektrických potenciálů a koncentrace vápníku v srdci s laserovou stabilizací

Investor: Czech Science Foundation

• MSM0021622402, plan (intention): Name: Časná diagnostika a léčba kardiovaskulárních chorob

Investor: Ministry of Education, Youth and Sports of the CR, Early diagnostics and treatment of cardiovascular diseases