BACKGROUND AND PURPOSE: Increased activity of the Na+/H+ -exchanger (NHE-1) in heart failure underlies raised [Na+]i causing disturbances of calcium handling. Inhibition of NHE-1, initiated at the onset of pressure/volume overload, prevents development of hypertrophy, heart failure and remodelling. We hypothesized that chronic inhibition of NHE-1, initiated at a later stage, would induce regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling. EXPERIMENTAL APPROACH: Development of heart failure in rabbits was monitored electrocardiographically and echocardiographically, after one or three months. Cardiac myocytes were also isolated. One group of animals were treated with cariporide (inhibitor of NHE-1) in the diet after one month. Cytoplasmic calcium, sodium and action potentials were measured with fluorescent markers and sarcoplasmic reticulum calcium content by rapid cooling. Calcium after-transients were elicited after rapid pacing. Sodium channel current (INa) was measured using patch-clamp techniques. KEY RESULTS: Hypertrophy and heart failure developed after one month and progressed during the next two months. After one month, dietary treatment with cariporide was initiated. Two months of treatment reduced hypertrophy and heart failure, duration of action potential QT-interval and QRS, and restored sodium and calcium handling and the incidence of calcium after-transients. In cardiac myocytes, parameters of INa were not changed by cariporide. CONCLUSION AND IMPLICATIONS: In rabbit hearts with hypertrophy and signs of heart failure one month after induction of pressure/volume overload, two months of dietary treatment with the NHE-1 inhibitor cariporide caused regression of hypertrophy, heart failure and ionic and electrophysiological remodelling.
BACKGROUND AND PURPOSE: Increased activity of the Na+/H+ -exchanger (NHE-1) in heart failure underlies raised [Na+]i causing disturbances of calcium handling. Inhibition of NHE-1, initiated at the onset of pressure/volume overload, prevents development of hypertrophy, heart failure and remodelling. We hypothesized that chronic inhibition of NHE-1, initiated at a later stage, would induce regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling. EXPERIMENTAL APPROACH: Development of heart failure in rabbits was monitored electrocardiographically and echocardiographically, after one or three months. Cardiac myocytes were also isolated. One group of animals were treated with cariporide (inhibitor of NHE-1) in the diet after one month. Cytoplasmic calcium, sodium and action potentials were measured with fluorescent markers and sarcoplasmic reticulum calcium content by rapid cooling. Calcium after-transients were elicited after rapid pacing. Sodium channel current (INa) was measured using patch-clamp techniques. KEY RESULTS:Hypertrophy and heart failure developed after one month and progressed during the next two months. After one month, dietary treatment with cariporide was initiated. Two months of treatment reduced hypertrophy and heart failure, duration of action potential QT-interval and QRS, and restored sodium and calcium handling and the incidence of calcium after-transients. In cardiac myocytes, parameters of INa were not changed by cariporide. CONCLUSION AND IMPLICATIONS: In rabbit hearts with hypertrophy and signs of heart failure one month after induction of pressure/volume overload, two months of dietary treatment with the NHE-1 inhibitor cariporide caused regression of hypertrophy, heart failure and ionic and electrophysiological remodelling.
Authors: María C Camilión de Hurtado; Enrique L Portiansky; Néstor G Pérez; Oscar R Rebolledo; Horacio E Cingolani Journal: Cardiovasc Res Date: 2002-03 Impact factor: 10.787
Authors: P Théroux; B R Chaitman; N Danchin; L Erhardt; T Meinertz; J S Schroeder; G Tognoni; H D White; J T Willerson; A Jessel Journal: Circulation Date: 2000-12-19 Impact factor: 29.690
Authors: U Zeymer; H Suryapranata; J P Monassier; G Opolski; J Davies; G Rasmanis; G Linssen; U Tebbe; R Schröder; R Tiemann; T Machnig; K L Neuhaus Journal: J Am Coll Cardiol Date: 2001-11-15 Impact factor: 24.094
Authors: Oscar H Cingolani; Néstor G Pérez; Irene L Ennis; María C Alvarez; Susana M Mosca; Guillermo R Schinella; Eduardo M Escudero; Gloria Cónsole; Horacio E Cingolani Journal: Pflugers Arch Date: 2011-08-26 Impact factor: 3.657
Authors: Vikram Prasad; John N Lorenz; Marian L Miller; Kanimozhi Vairamani; Michelle L Nieman; Yigang Wang; Gary E Shull Journal: J Mol Cell Cardiol Date: 2013-09-29 Impact factor: 5.000