title: Negative hemodynamic effects of pantoprazole at high infusion rates in mice.
abstract: BACKGROUND
  Pantoprazole has been shown to exert a negative inotropic effect in isolated myocardium. The purpose of this study was to evaluate the hemodynamic effects of pantoprazole in vivo in healthy myocardium and in the setting of heart failure.
  
  
  RESULTS
  Healthy mice and mice with heart failure 4 weeks after myocardial infarction induced by permanent LAD ligation were instrumented with a Millar Mikrotip conductance catheter to record pressure-volume loops. Pantoprazole was infused at rates of 3 and 10 mg/kg/min intravenously, and hemodynamic parameters were recorded. Infusion of pantoprazole at increasing rates lead to a significant decline of end systolic LV pressure by decreasing heart rate, myocardial contractility and arterial elastance. These effects were quick, beginning immediately with the infusion and usually reaching a plateau after 2 or 3 min of infusion. The effects on blood pressure and heart rate were of comparable size in healthy mice and mice with MI. However, in sham-operated mice, there was a compensatory increase in stroke volume that sufficed to maintain cardiac output at a constant level, which was missing in mice with MI. In 4 of 13 mice with MI infusion of 10 mg/kg/min pantoprazole lead to pump failure, which was lethal in 2 of these animals.
  
  
  CONCLUSIONS
  At higher infusion rates, pantoprazole is able to induce negative hemodynamic responses. In particular, in the setting of heart failure, these effects can lead to significant impairment of cardiac function. Therefore, high infusion rates of pantoprazole should be avoided especially in heart failure patients.
authors.affiliation: Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Unsöld
authors.forename: Nils
authors.initials: N
authors.lastname: Teucher
authors.forename: Michael
authors.initials: M
authors.lastname: Didié
authors.forename: Samuel
authors.initials: S
authors.lastname: Sossalla
authors.forename: Claudius
authors.initials: C
authors.lastname: Jacobshagen
authors.forename: Tim
authors.initials: T
authors.lastname: Seidler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schillinger
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuß
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000494:pharmacology*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole
keywords: Chronotrpy; Conductance catheter; Inotropy; Ischemic heart disease; Mouse; Myocardial infarction; Proton pump inhibitor