TY - JOUR

T1 - Effect of the antipsychotic drug haloperidol on arrhythmias during acute myocardial infarction in a porcine model

AU - Sattler, Stefan M.

AU - Lubberding, Anniek F.

AU - Kristensen, Charlotte B.

AU - Møgelvang, Rasmus

AU - Blanche, Paul

AU - Fink-Jensen, Anders

AU - Engstrøm, Thomas

AU - Kääb, Stefan

AU - Jespersen, Thomas

AU - Tfelt-Hansen, Jacob

PY - 2020

Y1 - 2020

N2 - Patients receiving psychiatric medication, like the antipsychotic drug haloperidol, are at an increased risk of sudden cardiac death (SCD). Haloperidol blocks the cardiac rapidly-activating delayed rectifier potassium current, thereby increasing electrical dispersion of repolarization which can potentially lead to arrhythmias. Whether these patients are also at a higher risk to develop SCD during an acute myocardial infarction (AMI) is unknown. AMI locally shortens action potential duration, which might further increase repolarization dispersion and increase the risk of arrhythmia in the presence of haloperidol compared to without. Our aim was to test whether treatment with haloperidol implies an increased risk of SCD when eventually experiencing AMI. Twenty-eight female Danish Landrace pigs were randomized into three groups: low dose haloperidol (0.1 mg/kg), high dose (1.0 mg/kg) or vehicle-control group. One hour after haloperidol/vehicle infusion, AMI was induced by balloon-occlusion of the mid-left anterior descending coronary artery and maintained for 120 min, followed by 60 min of reperfusion. VF occurred during occlusion in 7/11 pigs in the control group, 3/11 in the low dose (p = 0.198) and 2/6 in the high dose group (p = 0.335). High dose haloperidol significantly prolonged QT, and reduced heart rate, vascular resistance and blood pressure before and during AMI. Premature ventricular contractions in phase 1b during AMI were reduced with high dose haloperidol. AMI-induced arrhythmia was not aggravated in pigs with haloperidol treatment. Our results do not suggest that AMI is contributing to the excess mortality in patients treated with antipsychotic drugs seen in epidemiological studies.

AB - Patients receiving psychiatric medication, like the antipsychotic drug haloperidol, are at an increased risk of sudden cardiac death (SCD). Haloperidol blocks the cardiac rapidly-activating delayed rectifier potassium current, thereby increasing electrical dispersion of repolarization which can potentially lead to arrhythmias. Whether these patients are also at a higher risk to develop SCD during an acute myocardial infarction (AMI) is unknown. AMI locally shortens action potential duration, which might further increase repolarization dispersion and increase the risk of arrhythmia in the presence of haloperidol compared to without. Our aim was to test whether treatment with haloperidol implies an increased risk of SCD when eventually experiencing AMI. Twenty-eight female Danish Landrace pigs were randomized into three groups: low dose haloperidol (0.1 mg/kg), high dose (1.0 mg/kg) or vehicle-control group. One hour after haloperidol/vehicle infusion, AMI was induced by balloon-occlusion of the mid-left anterior descending coronary artery and maintained for 120 min, followed by 60 min of reperfusion. VF occurred during occlusion in 7/11 pigs in the control group, 3/11 in the low dose (p = 0.198) and 2/6 in the high dose group (p = 0.335). High dose haloperidol significantly prolonged QT, and reduced heart rate, vascular resistance and blood pressure before and during AMI. Premature ventricular contractions in phase 1b during AMI were reduced with high dose haloperidol. AMI-induced arrhythmia was not aggravated in pigs with haloperidol treatment. Our results do not suggest that AMI is contributing to the excess mortality in patients treated with antipsychotic drugs seen in epidemiological studies.

KW - Acute myocardial infarction

KW - Antipsychotic drugs

KW - Haloperidol

KW - Porcine model

KW - Sudden cardiac death

KW - Ventricular fibrillation

U2 - 10.1016/j.ijcha.2019.100455

DO - 10.1016/j.ijcha.2019.100455

M3 - Journal article

C2 - 32140549

AN - SCOPUS:85077389382

VL - 26

JO - IJC Heart and Vasculature

JF - IJC Heart and Vasculature

SN - 2352-9067

M1 - 100455

ER -