title: Right ventricular pacing improves right heart function in experimental pulmonary arterial hypertension: a study in the isolated heart.
abstract: Right heart failure in pulmonary arterial hypertension (PH) is associated with mechanical ventricular dyssynchrony, which leads to impaired right ventricular (RV) function and, by adverse diastolic interaction, to impaired left ventricular (LV) function as well. However, therapies aiming to restore synchrony by pacing are currently not available. In this proof-of-principle study, we determined the acute effects of RV pacing on ventricular dyssynchrony in PH. Chronic PH with right heart failure was induced in rats by injection of monocrotaline (80 mg/kg). To validate for PH-related ventricular dyssynchrony, rats (6 PH, 6 controls) were examined by cardiac magnetic resonance imaging (9.4 T), 23 days after monocrotaline or sham injection. In a second group (10 PH, 4 controls), the effects of RV pacing were studied in detail, using Langendorff-perfused heart preparations. In PH, septum bulging was observed, coinciding with a reversal of the transseptal pressure gradient, as observed in clinical PH. RV pacing improved RV systolic function, compared with unpaced condition (maximal first derivative of RV pressure: +8.5 + or - 1.3%, P < 0.001). In addition, RV pacing markedly decreased the pressure-time integral of the transseptal pressure gradient when RV pressure exceeds LV pressure, an index of adverse diastolic interaction (-24 + or - 9%, P < 0.01), and RV pacing was able to resynchronize time of RV and LV peak pressure (unpaced: 9.8 + or - 1.2 ms vs. paced: 1.7 + or - 2.0 ms, P < 0.001). Finally, RV pacing had no detrimental effects on LV function or coronary perfusion, and no LV preexcitation occurred. Taken together, we demonstrate that, in experimental PH, RV pacing improves RV function and diminishes adverse diastolic interaction. These findings provide a strong rationale for further in vivo explorations.
authors.affiliation: Department of Physiology, VU University Medical Center, Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: M Louis
authors.initials: ML
authors.lastname: Handoko
authors.forename: Regis R
authors.initials: RR
authors.lastname: Lamberts
authors.forename: Everaldo M
authors.initials: EM
authors.lastname: Redout
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.forename: Christa
authors.initials: C
authors.lastname: Boer
authors.forename: Warner S
authors.initials: WS
authors.lastname: Simonides
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: Nico
authors.initials: N
authors.lastname: Westerhof
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Allaart
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial; D002908:Chronic Disease; D004195:Disease Models, Animal; D006333:Heart Failure / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006346:Heart Septum / Q000473:pathology / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D016686:Monocrotaline; D009200:Myocardial Contraction; D010477:Perfusion; D051381:Rats; D015203:Reproducibility of Results; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right; D017725:Ventricular Pressure
chemical_list: D016686:Monocrotaline