title: Chronic pantoprazole administration and ischemia--reperfusion arrhythmias in vivo in rats--antiarrhythmic or arrhythmogenic?
abstract: BACKGROUND
  The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI pantoprazole on ventricular arrhythmias induced by either ischemia or ischemia-reperfusion (I/R) was studied.
  
  
  METHODS
  The left main coronary artery (LAD) was ligated for 30 or 10 min followed by a 30-min reperfusion in anesthetized rats. Rats were pretreated with pantoprazole (1.3 mg/kg) or vehicle by gastric gavage (daily for 3 weeks) before ligation. Serum electrolytes levels were measured by the end of the third week before coronary ligation. Lactate dehydrogenase (LDH) activity and nitric oxide (NO) concentrations were measured at the end of the ischemia and IR injury.
  
  
  RESULTS
  Pantoprazole caused significant hyperkalemia by the end of third week compared with vehicle-treated rats. After LAD ligation (30 min), ventricular premature contractions (VPC), ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded in rats of the vehicle ischemia group. Pantoprazole pretreatment aggravate these arrhythmias and increased mortality. A 10-min period of ischemia followed by a 30-min reperfusion induced high incidence of VT (100%) and VF (80%) in the vehicle-treated group. The group of rats administered pantoprazole had significantly lower incidence and durations of VT and VF together with reduction of mortality rate. Pantoprazole significantly reduced serum LDH activity and NO release from myocardial tissue after both ischemia and I/R injury.
  
  
  CONCLUSIONS
  Pantoprazole aggravated ischemia-induced arrhythmias but had a significant antiarrhythmic effect on I/R-induced ventricular arrhythmias.
authors: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors: Hala Salah
authors: HS
authors: Abdel-Kawy
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000633:toxicity; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006947:Hyperkalemia / Q000139:chemically induced; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D009569:Nitric Oxide / Q000097:blood; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D018879:Ventricular Premature Complexes / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000889:Anti-Arrhythmia Agents; D054328:Proton Pump Inhibitors; D009569:Nitric Oxide; D000077402:Pantoprazole; D007770:L-Lactate Dehydrogenase
keywords: Ischemia/reperfusion; Pantoprazole; Proton pump inhibitors; Ventricular arrhythmias