NOGOVÁ, Kateřina and Marie NOVÁKOVÁ. Acute effects of sigma receptor ligand haloperidol in rat and guinea pig isolated hearts. In New Frontiers in Cardiovascular Research. 8th ed. Kraków, Polsko: Polish Academy of Arts, 2008, p. 82-83, 1 pp.
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Basic information
Original name Acute effects of sigma receptor ligand haloperidol in rat and guinea pig isolated hearts
Name in Czech Akutní účinky ligandu sigma receptorů haloperidolu u izolovaných srdcí potkana a morčete
Authors NOGOVÁ, Kateřina and Marie NOVÁKOVÁ.
Edition 8. vyd. Kraków, Polsko, New Frontiers in Cardiovascular Research, p. 82-83, 1 pp. 2008.
Publisher Polish Academy of Arts
Other information
Original language English
Type of outcome Proceedings paper
Field of Study 30105 Physiology
Country of publisher Poland
Confidentiality degree is not subject to a state or trade secret
Organization unit Faculty of Medicine
Keywords in English isolated heart;rat;guinea pig;sigma receptor;haloperidol;arrhythmias
Tags arrhythmias, guinea pig, haloperidol, isolated heart, rat, sigma receptor
Tags International impact, Reviewed
Changed by Changed by: prof. MUDr. Marie Nováková, Ph.D., učo 1188. Changed: 28/1/2009 11:21.
Abstract
Sigma receptor ligands, mostly antipsychotics, can as an unwanted effect trigger episodes of cardiac arrhythmias - ventricular tachycardia, ventricular fibrillation, torsade de pointes, which occasionally culminate in sudden death. Mechanisms of these life-threatening side effects are not fully understood. Therefore we explored the role of typical sigma ligand haloperidol in susceptibility to develop arrhythmias on 3-D electrogram. Eleven adult male rats and eleven adult male guinea pigs were sacrificed under deep ether anesthesia. The hearts were perfused according to Langendorff with Krebs-Henseleit solution 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). This value was used for normalization of heart rate during the rest of experiment. Similarly, QT intervals were examined to determine L-QT. The incidence of arrhythmias was assessed according to Lambeth Conventions. Heart rate and QT interval showed similar changes in both models. Normalized heart rate declines in haloperidol applications and restores in washout. Almost all hearts exhibit L-QT. In guinea pig hearts, typical life-threatening arrhythmias occur; rat hearts show only premature ventricular beats in both haloperidol periods. This effect was attenuated in the next haloperidol phase. In conclusion, lengthened QT observed in our experimental models can explain the occurrence of arrhythmias. Unchanged QT interval in guinea pig hearts in the second haloperidol period can be reasoned by down-regulation of cardiac sigma receptors.
Abstract (in Czech)
Sigma receptor ligands, mostly antipsychotics, can as an unwanted effect trigger episodes of cardiac arrhythmias - ventricular tachycardia, ventricular fibrillation, torsade de pointes, which occasionally culminate in sudden death. Mechanisms of these life-threatening side effects are not fully understood. Therefore we explored the role of typical sigma ligand haloperidol in susceptibility to develop arrhythmias on 3-D electrogram. Eleven adult male rats and eleven adult male guinea pigs were sacrificed under deep ether anesthesia. The hearts were perfused according to Langendorff with Krebs-Henseleit solution 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). This value was used for normalization of heart rate during the rest of experiment. Similarly, QT intervals were examined to determine L-QT. The incidence of arrhythmias was assessed according to Lambeth Conventions. Heart rate and QT interval showed similar changes in both models. Normalized heart rate declines in haloperidol applications and restores in washout. Almost all hearts exhibit L-QT. In guinea pig hearts, typical life-threatening arrhythmias occur; rat hearts show only premature ventricular beats in both haloperidol periods. This effect was attenuated in the next haloperidol phase. In conclusion, lengthened QT observed in our experimental models can explain the occurrence of arrhythmias. Unchanged QT interval in guinea pig hearts in the second haloperidol period can be reasoned by down-regulation of cardiac sigma receptors.
Links
GA102/07/1473, research and development projectName: 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
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