Heart; Pulmonary Arterial Hypertension; Exercise; Myocardial Contraction
Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular resistance, affecting several arteries and arterioles. These changes are associated with increased right ventricular afterload and remodeling, characterized by severe hypertrophy, initially adaptive and derived from vascular pressure gradient.11. Vaillancourt M, Ruffenach G, Meloche J, Bonnet S. Adaptation and Remodelling of the Pulmonary Circulation in Pulmonary Hypertension. Can J Cardiol. 2015;31(4):407-15. doi: 10.1016/j.cjca.2014.10.023. , 22. Thenappan T, Ormiston ML, Ryan JJ, Archer SL. Pulmonary Arterial Hypertension: Pathogenesis and Clinical Management. BMJ. 2018;360:j5492. doi: 10.1136/bmj.j5492. Afterward, these alterations are accompanied by right ventricular dilation and impaired contractile performance, resulting in reduced ejection fraction and ventricular failure.33. Gomez-Arroyo JG, Farkas L, Alhussaini AA, Farkas D, Kraskauskas D, Voelkel NF, et al. The Monocrotaline Model of Pulmonary Hypertension in Perspective. Am J Physiol Lung Cell Mol Physiol. 2012;302(4):363-9. doi: 10.1152/ajplung.00212.2011. , 44. Kishiki K, Singh A, Narang A, Gomberg-Maitland M, Goyal N, Maffessanti F, et al. Impact of Severe Pulmonary Arterial Hypertension on the Left Heart and Prognostic Implications. J Am Soc Echocardiogr. 2019;32(9):1128-37. doi: 10.1016/j.echo.2019.05.008. Clinically, right ventricular size and function parameters alterations have a recognized association with bad prognosis in pulmonary arterial hypertension.44. Kishiki K, Singh A, Narang A, Gomberg-Maitland M, Goyal N, Maffessanti F, et al. Impact of Severe Pulmonary Arterial Hypertension on the Left Heart and Prognostic Implications. J Am Soc Echocardiogr. 2019;32(9):1128-37. doi: 10.1016/j.echo.2019.05.008.
During the PAH development, when right ventricular filling pressure has been increased, and cardiac output is deteriorating, there are concomitant volumetric and pressoric overload into the right ventricle.44. Kishiki K, Singh A, Narang A, Gomberg-Maitland M, Goyal N, Maffessanti F, et al. Impact of Severe Pulmonary Arterial Hypertension on the Left Heart and Prognostic Implications. J Am Soc Echocardiogr. 2019;32(9):1128-37. doi: 10.1016/j.echo.2019.05.008. These effects make the interventricular septum move to the left side, sustaining a paradoxical movement. Next, left ventricle (LV) ejection fraction and diastolic performance are affected, facing impaired early diastolic filling, reduced end-diastolic volume, and adverse remodeling.22. Thenappan T, Ormiston ML, Ryan JJ, Archer SL. Pulmonary Arterial Hypertension: Pathogenesis and Clinical Management. BMJ. 2018;360:j5492. doi: 10.1136/bmj.j5492. , 44. Kishiki K, Singh A, Narang A, Gomberg-Maitland M, Goyal N, Maffessanti F, et al. Impact of Severe Pulmonary Arterial Hypertension on the Left Heart and Prognostic Implications. J Am Soc Echocardiogr. 2019;32(9):1128-37. doi: 10.1016/j.echo.2019.05.008. Therefore, LV dysfunction configures a secondary and important effect from PAH onset.11. Vaillancourt M, Ruffenach G, Meloche J, Bonnet S. Adaptation and Remodelling of the Pulmonary Circulation in Pulmonary Hypertension. Can J Cardiol. 2015;31(4):407-15. doi: 10.1016/j.cjca.2014.10.023. , 22. Thenappan T, Ormiston ML, Ryan JJ, Archer SL. Pulmonary Arterial Hypertension: Pathogenesis and Clinical Management. BMJ. 2018;360:j5492. doi: 10.1136/bmj.j5492. , 55. Desai AS, Channick RN. Exercise in Patients with Pulmonary Arterial Hypertension. J Cardiopul Rehabil Prev. 2008;28(1):12-6. doi: 10.1097/01.hcr.0000311502.57022.73.
In terms of treatment, several pharmacological interventions have been adopted as therapeutic options for PAH. Despite this, PAH condition has been associated with a high prevalence of mortality and morbidity due to cardiac complications. Generally, PAH patients exhibit asthenia, fatigue, dyspnea, and poor scores of effort tolerance and quality of life.66. Coons JC, Pogue K, Kolodziej AR, Hirsch GA, George MP. Pulmonary Arterial Hypertension: A Pharmacotherapeutic Update. Curr Cardiol Rep. 2019;21(11):141. doi: 10.1007/s11886-019-1235-4. , 77. Vecchia LAD, Bussotti M. Exercise Training in Pulmonary Arterial Hypertension. J Thorac Dis. 2018;10(1):508-21. doi: 10.21037/jtd.2018.01.90.
Physical exercise training is a potential non-pharmacological tool to be used as a therapeutic option for cardiovascular diseases and complications.11. Vaillancourt M, Ruffenach G, Meloche J, Bonnet S. Adaptation and Remodelling of the Pulmonary Circulation in Pulmonary Hypertension. Can J Cardiol. 2015;31(4):407-15. doi: 10.1016/j.cjca.2014.10.023. , 77. Vecchia LAD, Bussotti M. Exercise Training in Pulmonary Arterial Hypertension. J Thorac Dis. 2018;10(1):508-21. doi: 10.21037/jtd.2018.01.90. Several physical training protocols have been used as promissory interventions in PAH experiments. Continuous aerobic exercise protocols promoted beneficial effects in the right ventricle and pulmonary artery remodeling.88. Colombo R, Siqueira R, Becker CU, Fernandes TG, Pires KM, Valença SS, et al. Effects of Exercise on Monocrotaline-induced Changes in Right Heart Function and Pulmonary Artery Remodeling in Rats. Can J Physiol Pharmacol. 2013;91(1):38-44. doi: 10.1139/cjpp-2012-0261.
9. Vieira JS, Cunha TF, Paixão NA, Dourado PM, Carrascoza LS, Bacurau AVN, et al. Exercise Intolerance Establishment in Pulmonary Hypertension: Preventive Effect of Aerobic Exercise Training. Life Sci. 2020;261:118298. doi: 10.1016/j.lfs.2020.118298. - 1010. Silva FJ, Drummond FR, Fidelis MR, Freitas MO, Leal TF, Rezende LMT, et al. Continuous Aerobic Exercise Prevents Detrimental Remodeling and Right Heart Myocyte Contraction and Calcium Cycling Dysfunction in Pulmonary Artery Hypertension. J Cardiovasc Pharmacol. 2021;77(1):69-78. doi: 10.1097/FJC.0000000000000928. Likewise, high-intensity interval training (HIIT) attenuated right ventricle systolic pressure and remodeling and lowered total pulmonary resistance in a rat model of monocrotaline (MCT)-induced PAH.1111. Brown MB, Neves E, Long G, Graber J, Gladish B, Wiseman A, et al. High-Intensity Interval Training, but not Continuous Training, Reverses Right Ventricular Hypertrophy and Dysfunction in a Rat Model of Pulmonary Hypertension. Am J Physiol Regul Integr Comp Physiol. 2017;312(2):197-210. doi: 10.1152/ajpregu.00358.2016. On the other hand, the potential impacts of exercise training interventions on LV aspects are few clarified in experimental conditions of pulmonary arterial hypertension.
In the current edition of the Arquivos Brasileiros de Cardiologia , Soares et al.1212. Soares LL, Leite LB, Ervilha LOG, Silva BAF, Freitas MO, Pontes AMO, et al. O Treinamento Físico Resistido Atenua as Disfunções Ventriculares Esquerdas em Modelo de Hipertensão Arterial Pulmonar. Arq Bras Cardiol. 2022; 119(4):574-584. analyzed the influence of resistance exercise training on LV remodeling and cardiomyocyte performance in rats during the development of monocrotaline (MCT)-induced PAH. In this elegant study, the Authors found that resistance exercise progressively increased tolerance to physical effort during the development of PAH in rats submitted to two injections of MCT (20 mg/kg) interspaced over seven days. Compared to control counterparts, trained PAH-animals exhibited later-onset heart failure signals. Likewise, resistance exercise training improved LV ejection fraction, cardiomyocyte contraction, and relaxation velocities. These improvements were accompanied decreased amount of type I collagen and increased type III collagen in LV samples from trained PAH-animals. Myocardial collagen fibers have distinct biomechanical differences; collagen I fibers confer higher stiffness, while type III collagen is associated with increased susceptibility to mechanical deformation,1313. Silva DCT, Lima-Leopoldo AP, Leopoldo AS, Campos DHS, Nascimento AF, Oliveira Junior SA, et al. Influence of Term of Exposure to High-fat diet-induced Obesity on Myocardial Collagen Type I and III. Arq Bras Cardiol. 2014;102(2):157-63. doi: 10.5935/abc.20130232. , 1414. Oliveira SA Jr, Dal Pai M, Guizoni DM, Torres BP, Martinez PF, Campos DHS, et al. Effects of AT1 Receptor Antagonism on Interstitial and Ultrastructural Remodeling of Heart in Response to a Hypercaloric Diet. Physiol Rep. 2019;7(1):e13964. doi: 10.14814/phy2.13964. which could be related to better LV contractile performance.
Therefore, low- to moderate-intensity resistance exercise training has adjuvant and cardioprotective effects in controlling LV remodeling secondary to MCT-induced PAH. Based on this, similar interventions may effectively minimize cardiac complications associated with PAH. On the other hand, as exercise training parameters vary and may sustain multiple protocols, it is necessary to better characterize demands relative to speed and intensity, as also discussed by the authors,1212. Soares LL, Leite LB, Ervilha LOG, Silva BAF, Freitas MO, Pontes AMO, et al. O Treinamento Físico Resistido Atenua as Disfunções Ventriculares Esquerdas em Modelo de Hipertensão Arterial Pulmonar. Arq Bras Cardiol. 2022; 119(4):574-584. besides frequency and duration. Further studies will contribute to elucidating the effects of diverse resistance exercise training protocols on cardiopulmonary disorders derived from MCT-induced PAH.
Acknowledgments
Universidade Federal de Mato Grosso do Sul – UFMS/MEC – Brasil; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) - Código de Financiamento 001, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Referências
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1Vaillancourt M, Ruffenach G, Meloche J, Bonnet S. Adaptation and Remodelling of the Pulmonary Circulation in Pulmonary Hypertension. Can J Cardiol. 2015;31(4):407-15. doi: 10.1016/j.cjca.2014.10.023.
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2Thenappan T, Ormiston ML, Ryan JJ, Archer SL. Pulmonary Arterial Hypertension: Pathogenesis and Clinical Management. BMJ. 2018;360:j5492. doi: 10.1136/bmj.j5492.
-
3Gomez-Arroyo JG, Farkas L, Alhussaini AA, Farkas D, Kraskauskas D, Voelkel NF, et al. The Monocrotaline Model of Pulmonary Hypertension in Perspective. Am J Physiol Lung Cell Mol Physiol. 2012;302(4):363-9. doi: 10.1152/ajplung.00212.2011.
-
4Kishiki K, Singh A, Narang A, Gomberg-Maitland M, Goyal N, Maffessanti F, et al. Impact of Severe Pulmonary Arterial Hypertension on the Left Heart and Prognostic Implications. J Am Soc Echocardiogr. 2019;32(9):1128-37. doi: 10.1016/j.echo.2019.05.008.
-
5Desai AS, Channick RN. Exercise in Patients with Pulmonary Arterial Hypertension. J Cardiopul Rehabil Prev. 2008;28(1):12-6. doi: 10.1097/01.hcr.0000311502.57022.73.
-
6Coons JC, Pogue K, Kolodziej AR, Hirsch GA, George MP. Pulmonary Arterial Hypertension: A Pharmacotherapeutic Update. Curr Cardiol Rep. 2019;21(11):141. doi: 10.1007/s11886-019-1235-4.
-
7Vecchia LAD, Bussotti M. Exercise Training in Pulmonary Arterial Hypertension. J Thorac Dis. 2018;10(1):508-21. doi: 10.21037/jtd.2018.01.90.
-
8Colombo R, Siqueira R, Becker CU, Fernandes TG, Pires KM, Valença SS, et al. Effects of Exercise on Monocrotaline-induced Changes in Right Heart Function and Pulmonary Artery Remodeling in Rats. Can J Physiol Pharmacol. 2013;91(1):38-44. doi: 10.1139/cjpp-2012-0261.
-
9Vieira JS, Cunha TF, Paixão NA, Dourado PM, Carrascoza LS, Bacurau AVN, et al. Exercise Intolerance Establishment in Pulmonary Hypertension: Preventive Effect of Aerobic Exercise Training. Life Sci. 2020;261:118298. doi: 10.1016/j.lfs.2020.118298.
-
10Silva FJ, Drummond FR, Fidelis MR, Freitas MO, Leal TF, Rezende LMT, et al. Continuous Aerobic Exercise Prevents Detrimental Remodeling and Right Heart Myocyte Contraction and Calcium Cycling Dysfunction in Pulmonary Artery Hypertension. J Cardiovasc Pharmacol. 2021;77(1):69-78. doi: 10.1097/FJC.0000000000000928.
-
11Brown MB, Neves E, Long G, Graber J, Gladish B, Wiseman A, et al. High-Intensity Interval Training, but not Continuous Training, Reverses Right Ventricular Hypertrophy and Dysfunction in a Rat Model of Pulmonary Hypertension. Am J Physiol Regul Integr Comp Physiol. 2017;312(2):197-210. doi: 10.1152/ajpregu.00358.2016.
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12Soares LL, Leite LB, Ervilha LOG, Silva BAF, Freitas MO, Pontes AMO, et al. O Treinamento Físico Resistido Atenua as Disfunções Ventriculares Esquerdas em Modelo de Hipertensão Arterial Pulmonar. Arq Bras Cardiol. 2022; 119(4):574-584.
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13Silva DCT, Lima-Leopoldo AP, Leopoldo AS, Campos DHS, Nascimento AF, Oliveira Junior SA, et al. Influence of Term of Exposure to High-fat diet-induced Obesity on Myocardial Collagen Type I and III. Arq Bras Cardiol. 2014;102(2):157-63. doi: 10.5935/abc.20130232.
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14Oliveira SA Jr, Dal Pai M, Guizoni DM, Torres BP, Martinez PF, Campos DHS, et al. Effects of AT1 Receptor Antagonism on Interstitial and Ultrastructural Remodeling of Heart in Response to a Hypercaloric Diet. Physiol Rep. 2019;7(1):e13964. doi: 10.14814/phy2.13964.
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Short Editorial related to the article: Resistance Exercise Training Mitigates Left Ventricular Dysfunctions in Pulmonary Artery Hypertension Model
Publication Dates
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Publication in this collection
21 Oct 2022 -
Date of issue
Oct 2022