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Heart rate reduction improves biventricular function and interactions in experimental pulmonary hypertension.
. 2018 03 01; 314(3):H542-H551.

Abstract

The objective of the present study was to investigate mechanisms of heart rate (HR) reduction on biventricular function and interactions in experimental pulmonary arterial hypertension (PAH). We compared cardiac cycle mechanics and interventricular interactions in 15 sham, 8 monocrotaline-PAH, 9 PAH + carvedilol, and 8 PAH + ivabradine rats. We used echocardiography to assess biventricular function, timing of cardiac cycle events, and septal position in PAH rats and related HR reduction effects on biventricular function measured by echocardiography and conductance catheter. HR was 302 beats/min in PAH + carvedilol rats and 303 beats/min in PAH + ivabradine rats versus 359 beats/min in PAH rats (P < 0.01). Sham rats showed temporal alignment between right ventricular (RV) and left ventricular (LV) events, whereas PAH rats showed increased biventricular isovolumic contraction times (ICTs), delayed RV peak radial motion, and impaired early relaxation. Temporal malalignment was associated with decreased tricuspid and mitral diastolic annular peak velocities (3.7 vs. 6.4 and 3.4 vs. 5.3 cm/s, respectively, P < 0.001), delayed and shortened biventricular filling, and reduced early diastolic LV filling velocity (0.56 vs. 0.81 cm/s, P < 0.01). LV eccentricity index was increased at systole (2.0 vs. 1.2, P < 0.001), early diastole (2.1 vs. 1.1, P < 0.001), and end diastole (1.6 vs. 1.1, P < 0.001) in PAH versus sham rats. HR reduction with carvedilol and ivabradine shortened biventricular ICTs and the time to biventricular peak radial motion, improved RV relaxation, and increased early diastolic LV filling through reduced interventricular interaction and improved timing. These improvements corresponded with enhanced hemodynamics (increased cardiac output, RV contractility, and diastolic relaxation). In conclusion, HR reduction by carvedilol and ivabradine improves biventricular filling and hemodynamics in experimental PAH through realignment of RV-LV cardiac cycle events and improved interventricular interactions. NEW & NOTEWORTHY Carvedilol improves biventricular function in experimental pulmonary arterial hypertension, but the mechanisms of heart rate reduction versus β-blocker effect are inadequately defined. Here, we demonstrate that reducing heart rate using either carvedilol or ivabradine (hyperpolarization-activated current inhibitor without β-blocker effect) improves right ventricular filling and biventricular hemodynamics through the realignment of right ventricular-left ventricular cardiac cycle events and improved interventricular interactions.

Authors+Show Affiliations

The Labatt Family Heart Center, Division of Cardiology and Cardiovascular Surgery, Hospital for Sick Children and University of Toronto , Toronto, Ontario , Canada.The Labatt Family Heart Center, Division of Cardiology and Cardiovascular Surgery, Hospital for Sick Children and University of Toronto , Toronto, Ontario , Canada.The Labatt Family Heart Center, Division of Cardiology and Cardiovascular Surgery, Hospital for Sick Children and University of Toronto , Toronto, Ontario , Canada.The Labatt Family Heart Center, Division of Cardiology and Cardiovascular Surgery, Hospital for Sick Children and University of Toronto , Toronto, Ontario , Canada.The Labatt Family Heart Center, Division of Cardiology and Cardiovascular Surgery, Hospital for Sick Children and University of Toronto , Toronto, Ontario , Canada.Institució Catalana de Recerca i Estudis Avançats, Barcelona , Spain. Department of Information and Communication Technologies, Universitat Pompeu Fabra , Barcelona , Spain.The Labatt Family Heart Center, Division of Cardiology and Cardiovascular Surgery, Hospital for Sick Children and University of Toronto , Toronto, Ontario , Canada.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29146614

Citation

Gomez, Olga, et al. "Heart Rate Reduction Improves Biventricular Function and Interactions in Experimental Pulmonary Hypertension." American Journal of Physiology. Heart and Circulatory Physiology, vol. 314, no. 3, 2018, pp. H542-H551.
Gomez O, Okumura K, Honjo O, et al. Heart rate reduction improves biventricular function and interactions in experimental pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2018;314(3):H542-H551.
Gomez, O., Okumura, K., Honjo, O., Sun, M., Ishii, R., Bijnens, B., & Friedberg, M. K. (2018). Heart rate reduction improves biventricular function and interactions in experimental pulmonary hypertension. American Journal of Physiology. Heart and Circulatory Physiology, 314(3), H542-H551. https://doi.org/10.1152/ajpheart.00493.2017
Gomez O, et al. Heart Rate Reduction Improves Biventricular Function and Interactions in Experimental Pulmonary Hypertension. Am J Physiol Heart Circ Physiol. 2018 03 1;314(3):H542-H551. PubMed PMID: 29146614.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heart rate reduction improves biventricular function and interactions in experimental pulmonary hypertension. AU - Gomez,Olga, AU - Okumura,Kenichi, AU - Honjo,Osami, AU - Sun,Mei, AU - Ishii,Ryo, AU - Bijnens,Bart, AU - Friedberg,Mark K, Y1 - 2017/12/04/ PY - 2017/11/18/pubmed PY - 2019/1/8/medline PY - 2017/11/18/entrez KW - carvedilol KW - heart rate reduction, interventricular interactions KW - ivabradine KW - pulmonary hypertension SP - H542 EP - H551 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 314 IS - 3 N2 - The objective of the present study was to investigate mechanisms of heart rate (HR) reduction on biventricular function and interactions in experimental pulmonary arterial hypertension (PAH). We compared cardiac cycle mechanics and interventricular interactions in 15 sham, 8 monocrotaline-PAH, 9 PAH + carvedilol, and 8 PAH + ivabradine rats. We used echocardiography to assess biventricular function, timing of cardiac cycle events, and septal position in PAH rats and related HR reduction effects on biventricular function measured by echocardiography and conductance catheter. HR was 302 beats/min in PAH + carvedilol rats and 303 beats/min in PAH + ivabradine rats versus 359 beats/min in PAH rats (P < 0.01). Sham rats showed temporal alignment between right ventricular (RV) and left ventricular (LV) events, whereas PAH rats showed increased biventricular isovolumic contraction times (ICTs), delayed RV peak radial motion, and impaired early relaxation. Temporal malalignment was associated with decreased tricuspid and mitral diastolic annular peak velocities (3.7 vs. 6.4 and 3.4 vs. 5.3 cm/s, respectively, P < 0.001), delayed and shortened biventricular filling, and reduced early diastolic LV filling velocity (0.56 vs. 0.81 cm/s, P < 0.01). LV eccentricity index was increased at systole (2.0 vs. 1.2, P < 0.001), early diastole (2.1 vs. 1.1, P < 0.001), and end diastole (1.6 vs. 1.1, P < 0.001) in PAH versus sham rats. HR reduction with carvedilol and ivabradine shortened biventricular ICTs and the time to biventricular peak radial motion, improved RV relaxation, and increased early diastolic LV filling through reduced interventricular interaction and improved timing. These improvements corresponded with enhanced hemodynamics (increased cardiac output, RV contractility, and diastolic relaxation). In conclusion, HR reduction by carvedilol and ivabradine improves biventricular filling and hemodynamics in experimental PAH through realignment of RV-LV cardiac cycle events and improved interventricular interactions. NEW & NOTEWORTHY Carvedilol improves biventricular function in experimental pulmonary arterial hypertension, but the mechanisms of heart rate reduction versus β-blocker effect are inadequately defined. Here, we demonstrate that reducing heart rate using either carvedilol or ivabradine (hyperpolarization-activated current inhibitor without β-blocker effect) improves right ventricular filling and biventricular hemodynamics through the realignment of right ventricular-left ventricular cardiac cycle events and improved interventricular interactions. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/29146614/Heart_rate_reduction_improves_biventricular_function_and_interactions_in_experimental_pulmonary_hypertension_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.00493.2017?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -