Effects of different proton pump inhibitors on cardiac contractility in isolated human failing myocardium

Abstract

Aim. Proton pump inhibitors (PPI), e.g. pantoprazole (PP), esomeprazole (EP) and omeprazole (OP), work as anti-ulcer/gastrointestinal reflux drugs. Also, they are widely used in postoperative care of patients in cardiac surgery to prevent upper gastrointestinal bleeding. Therefore, in western industrial countries they play a major economic role, representing one of the most important drugs in open heart cardiac surgery. Methods. Intact muscle strips (n=32) were isolated from the right ventricle wall of failing human hearts. In four different groups (PP, EP, OP, control group, each n=8), force amplitudes were recorded at a frequency of 60 beats per minute (bpm) with increasing PPI concentrations (0 to 320 mu m/mL). Results. In isometrically contracting muscle strips, significant negative inotropic effects were observed in the presence of all three PPI-groups (PP, EP and OP) with doses of 2.5 mu g/mL and higher compared to the control group (p < 0.05 each). With high doses (320 mu m/mL), force amplitudes could be almost completely depressed. The half maximal inhibitory concentration (IC(50)) for EP was 35.7 (confidence interval: 17.3-73.6) vs. OP 29.3 (6.8-126.6) vs. PP 25.1 (14.6-43.1) mu g/mL (n.s.). No significant differences were found between the different proton pump inhibitors (PP, EP, OP) throughout the range of all concentrations. Relaxation was unpaired in all PPI subgroups with prolonged time to 90% relaxation (RT90%) and maximum relaxation velocity (-df/dt) was reduced, too. These effects were partially reversible after wash-out of the drugs. Conclusion. We conclude that proton pump inhibitors show significant negative inotropic effects on isolated human failing myocardium. There is no apparent difference seen in the magnitude of the effects of each PPI-group. Further, in-vivo investigations are necessary to reveal the clinical evidence of PPI's negative inotropic effects, e.g. in cardio-surgical patients with heart failure.