Abstract 4027: Negative Hemodynamic Effects of Pantoprazole at High Infusion Rates in Mice
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.
Methods: 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 from 0.3 to 10 mg/kg/min intravenously and hemodynamic parameters were recorded. Because of the different pharma-cokinetics of mice and men these rates should correspond to 4 –5 times lower rates in humans which can be reached during bolus applications.
Results: Infusion of pantoprazole at increasing rates lead to a significant decline in end systolic LV pressure (84±3% of baseline, n=9, p<0.01 at 10mg/kg/min). The decrease in blood pressure was induced by different hemodynamic effects. Pantoprazole infusion at 10mg/kg/min induced sinus bradycardia (HR 82±2% of baseline, n=9, p<0.01), reduced arterial elastance (69±3% of baseline, n=9, p<0.01) and depressed contractility (dp/dtmax 73±5% of baseline, n=9, p<0.01). These effects were quick, beginning immediately with the infusion and usually reaching a plateau after 2 or 3 minutes of infusion. The effects were of comparable size in healty mice and mice with MI. However in 4 out of 13 mice with MI infusion of 10mg/kg/min pantozole rapidly lead to pump failure which was lethal in 2 of the animals. The 2 other mice recovered after the infusion was stopped immediately. After stopping the continuous infusion the effects were at least partially reversible with a relatively fast kinetics.
Conclusion: At higher infusion rates pantoprazole is able to induce negative hemodynamic responses. Especially 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. As the observed effects are rate-dependent and reversible lower infusion rates seem to avoid the possible problems.