title: Inhibition of Na+-H+ exchange by cariporide reduces inflammation and heart failure in rabbits with myocardial infarction.
abstract: The aim of this study was to assess the effects of the Na+-H+ exchange inhibitor cariporide on left ventricular (LV) morphology and function as well as inflammation in rabbits with heart failure. Rabbits with myocardial infarction (MI) and sham controls were randomized to receive either standard chow or chow supplemented with cariporide for 9 weeks. LV morphology was determined by echocardiography. LV systolic and diastolic function was assessed under load-dependent and -independent conditions by analysis of LV pressure-volume loops using piezo-electric crystals. Plasma concentrations of C-reactive protein and aldosterone were measured. Rabbits with MI developed LV dilatation that was reduced by cariporide. Systolic and diastolic LV function was impaired in rabbits with MI when compared to sham, as indicated by a decreased dP/dtmax (MI: 3537 +/- 718 mmHg s(-1), sham: 5839 +/- 247 mmHg s(-1), P < 0.05), the load-independent preload recruitable stroke work (PRSW)(MI: 22 +/-7 mmHg, sham: 81 +/- 23 mmHg, P < 0.05) and a reduction in the time constant of relaxation tau (tau) (MI: 27+/-1 ms, sham: 17+/-1 ms, P < 0.05), and significantly improved by cariporide (dP/dtmax: 4586 +/- 374 mmHg s(-1), PRSW: 67 +/- 18 mmHg, tau: 20 +/- 2 ms; P < 0.05 vs MI/control). Induction of MI was associated with an increase in aldosterone and CRP, indicating activation of the neurohormonal and the inflammatory system that were largely reduced by cariporide. Cariporide improves LV morphology and function post MI and suppresses inflammation and neurohormonal activation in congestive heart failure (CHF). Na+-H+ exchange inhibition may represent a new pharmaceutical approach for the treatment of CHF.
authors.affiliation: Aventis Pharma Deutschland GmbH, 65926 Frankfurt, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Rungwerth
authors.forename: Ursula
authors.initials: U
authors.lastname: Schindler
authors.forename: Martin
authors.initials: M
authors.lastname: Gerl
authors.forename: Stefan
authors.initials: S
authors.lastname: Schäfer
authors.forename: Thomas
authors.initials: T
authors.lastname: Licher
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Busch
authors.forename: Hartmut
authors.initials: H
authors.lastname: Ruetten
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis* / Q000378:metabolism; D004562:Electrocardiography; D006146:Guanidines / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*; D015996:Survival Rate; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D000450:Aldosterone; C093373:cariporide; D002097:C-Reactive Protein