Thorac Cardiovasc Surg 2005; 53 - MP25
DOI: 10.1055/s-2005-861970

The proton pump inhibitor pantoprazole impairs contractility of human and rabbit myocardium

N Teucher 1, S Sossalla 2, S Kettlewell 3, C Sag 2, H Schwörer 4, H Dörge 5, H Kögler 2, L Maier 2, G Smith 3, G Hasenfuss 2, F Schöndube 5, W Schillinger 2
  • 1Universität Göttingen, Herzzentrum Goettingen, Thorax-, Herz- und Gefäßchirurgie, Kardiologie und Pneumonologie, Göttingen
  • 2Universität Göttingen, Herzzentrum Göttingen, Kardiologie und Pneumonologie, Göttingen
  • 3University of Glasgow, Institute of Biomedical and Life Sciences, Glasgow, UK
  • 4Universität Göttingen, Gastroenterologie, Göttingen
  • 5Universität Göttingen, Herzzentrum Göttingen, Thorax-, Herz- und Gefäßchirurgie, Göttingen

Proton pump inhibitors like pantoprazole (PP) are widely used for treatment and prophylaxis of acute upper gastrointestinal bleeding after cardiac surgery. We investigated the effect of PP in isometrically contracting human myocardium and rabbit isolated cardiomyocytes.

Trabeculae were dissected from the right auricle of patients that underwent cardiac surgery on extracorporal circulation for different reasons. The specimens were superfused with Krebs-Henseleit-Buffer (37°C, pH 7.35, 1mM Ca2+). PP (0.625–40µg/ml) decreased force development (mean±SEM: 50µg/ml PP (n=15) 2.07±0.45 vs. control (n=15) 5.35±0.69 mN/mm2; p<0.05). Similar results were obtained in ventricular trabeculae from patients with NYHA-IV heart failure that underwent cardiac transplantation as well as in ventricular trabeculae dissected from healthy rabbits.

In rabbit isolated ventricular cardiomyocytes, PP decreases the affinity of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) towards calcium (Kd: mean±SEM: 40µg/ml PP (n=9) 3.58×10–7±1.45×10–8 vs. control (n=9) 3.95×10–7±1.18×10–8µmol/l; p<0.05). Preliminary data in skinned fibers indicate additional effects of PP by interaction with cardiac myofilaments.

These data indicate depression of contractile function of human and rabbit myocardium by interaction with proteins involved in Ca2+-homeostasis and with cardiac myofilaments. Although the underlying mechanisms are still under investigation, the present study suggests a potential risk for cardiac surgery patients with reduced ventricular function when treated even with pantoprazole at clinically relevant dosage.