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Negative hemodynamic effects of pantoprazole at high infusion rates in mice
Bernhard Unsöld1, Nils Teucher, Michael Didié
1Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
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 And 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.
Conclusion:
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.
Insights
High-dose pantoprazole infusion negatively impacts cardiac function, particularly in heart failure models. This proton pump inhibitor can cause significant hemodynamic decline and pump failure, underscoring caution in vulnerable patients.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Pantoprazole demonstrates a negative inotropic effect on isolated myocardium.
- The in vivo hemodynamic impact of pantoprazole in healthy and failing hearts requires evaluation.
Purpose of the Study:
- To assess the in vivo hemodynamic effects of pantoprazole in healthy myocardium.
- To evaluate pantoprazole's effects in a heart failure model.
Main Methods:
- Utilized Millar Mikrotip conductance catheter in mice to record pressure-volume loops.
- Administered pantoprazole intravenously at 3 and 10 mg/kg/min in healthy and myocardial infarction (MI) models.
- Monitored hemodynamic parameters including heart rate, contractility, and arterial elastance.
Main Results:
- Pantoprazole infusion decreased left ventricular end-systolic pressure, heart rate, myocardial contractility, and arterial elastance.
- Effects were rapid, reaching a plateau within 2-3 minutes.
- Heart failure mice showed impaired compensatory stroke volume increase and a higher incidence of pump failure (lethal in 2/13 at 10 mg/kg/min).
Conclusions:
- High-rate pantoprazole infusion induces adverse hemodynamic responses.
- Significant cardiac function impairment can occur in heart failure patients.
- Avoid high infusion rates of pantoprazole, especially in patients with heart failure.
