PURPOSE: The purpose of the study was to determine the influence of oxidative phosphorylation uncoupler FCCP (carbonyl cyanide p-trifluoromethoxy-phenylhydrazone) and F1F0-ATPase inhibitor oligomycin on the parameters of electromechanical activity in human myocardium. MATERIAL AND METHODS: The experiments were performed on isolated human ventricle strips from patients undergoing cardiac corrective open heart surgery. Effect of investigative agents was registered using conventional method of registration of cardiac electromechanical activity. RESULTS: FCCP (10(-9), 10(-8), 10(-7), 10(-6) mol/L) caused the gradual reduction of contraction force (P). The maximal decrement of P (to 8.3 +/- 3.1% (n=5) vs control), was achieved at 10(-6) mol/L FCCP concentration. The duration of action potential at 50% of repolarization (AP50) was decreased only at 10(-7) and 10(-6) mol/L FCCP concentrations, i.e. to 94.3 +/- 1.9% and 55.5 +/- 3.1% (n=4), respectively, vs control. Oligomycin (2 x 10(-5) mol/L) alone decreased P only to 77.8 +/- 5.1% (n=5) and slightly reduced AP50 to 94.2 +/- 6.2% (n=4) vs control. Application of FCCP on top of oligomycin decreased P at the smaller extent than under the action of FCCP alone: the highest concentration of FCCP (10(-6) mol/L) reduced P to 21.1 +/- 4.5% (n=5) vs effect of oligomycin. The duration of AP50 was also less shortened after application of FCCP in the presence of oligomycin. The highest concentration of FCCP (10(-6) mol/L) reduced AP50 to 73.5 +/- 10.1% (n=4) vs effect of oligomycin. CONCLUSIONS: In conclusion, our data show that the inhibition of F1F0-ATPase reduces the impairment of electromechanical activity caused by oxidative phosphorylation uncoupler FCCP in human myocardium.
PURPOSE: The purpose of the study was to determine the influence of oxidative phosphorylation uncoupler FCCP (carbonyl cyanide p-trifluoromethoxy-phenylhydrazone) and F1F0-ATPase inhibitor oligomycin on the parameters of electromechanical activity in human myocardium. MATERIAL AND METHODS: The experiments were performed on isolated human ventricle strips from patients undergoing cardiac corrective open heart surgery. Effect of investigative agents was registered using conventional method of registration of cardiac electromechanical activity. RESULTS:FCCP (10(-9), 10(-8), 10(-7), 10(-6) mol/L) caused the gradual reduction of contraction force (P). The maximal decrement of P (to 8.3 +/- 3.1% (n=5) vs control), was achieved at 10(-6) mol/L FCCP concentration. The duration of action potential at 50% of repolarization (AP50) was decreased only at 10(-7) and 10(-6) mol/L FCCP concentrations, i.e. to 94.3 +/- 1.9% and 55.5 +/- 3.1% (n=4), respectively, vs control. Oligomycin (2 x 10(-5) mol/L) alone decreased P only to 77.8 +/- 5.1% (n=5) and slightly reduced AP50 to 94.2 +/- 6.2% (n=4) vs control. Application of FCCP on top of oligomycin decreased P at the smaller extent than under the action of FCCP alone: the highest concentration of FCCP (10(-6) mol/L) reduced P to 21.1 +/- 4.5% (n=5) vs effect of oligomycin. The duration of AP50 was also less shortened after application of FCCP in the presence of oligomycin. The highest concentration of FCCP (10(-6) mol/L) reduced AP50 to 73.5 +/- 10.1% (n=4) vs effect of oligomycin. CONCLUSIONS: In conclusion, our data show that the inhibition of F1F0-ATPase reduces the impairment of electromechanical activity caused by oxidative phosphorylation uncoupler FCCP in human myocardium.
Authors: Achilleas Floudas; Aine Gorman; Nuno Neto; Michael G Monaghan; Zoe Elliott; Ursula Fearon; Viviana Marzaioli Journal: Front Med (Lausanne) Date: 2022-03-14