Chronic Pantoprazole Administration and Ischemia–Reperfusion Arrhythmias In Vivo in Rats—Antiarrhythmic or Arrhythmogenic?

Abstract

SUMMARYBackground: 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. Conclusion: Pantoprazole aggravated ischemia-induced arrhythmias but had a significant antiarrhythmic effect on I/R-induced ventricular arrhythmias.

Associations Between Late-Onset Preeclampsia and the Use of Calcium-Based Antacids and Proton Pump Inhibitors During Pregnancy: A Prospective Cohort Study

“…We did not identify other studies with similar results on calcium in early pregnancy, but slightly increased risks of overall preeclampsia associated with PPI use in pregnancy were also observed in other studies, 14–16 as summarized in a recent meta-analysis (RR 1.27, 95% CI 1.23–1.31). 51 Animal and in vitro studies showed that PPIs, particularly pantoprazole, have a negative impact on vascular endothelium and renal tissue, 52 aggravate ischaemia-induced arrhythmias, 53 and may be responsible for a depression of cardiac contractility, 54 providing a possible biological mechanism for the association observed. However, these results may also be biased by confounding by indication, as illustrated by the attenuated RR in comparisons with an H 2 RA-exposed group in a nationwide cohort study in South Korea.…”