Exercise preconditioning prevents left ventricular dysfunction and remodeling in monocrotaline-induced pulmonary hypertension

Abstract

Background: Despite pulmonary arterial hypertension (PAH) directly affects the right ventricle (RV), important structural, functional, and molecular changes also occur in left ventricle (LV). The objective of our study was to analyze the hypothetical cardioprotective effects of exercise preconditioning on LV in rats with monocrotaline (MCT)-induced PAH. Methods: Forty male Wistar rats were randomly separated in sedentary (SED) and trained group (EX; running sessions of 60 min/day, 5 days/wk, at 25 m/min, for 4 weeks). After 4 weeks, animals were injected with MCT (60 mg/kg; SED + MCT; EX + MCT) or vehicle (SED + V). Following an additional period of 4 weeks where all animals remained sedentary, we completed LV hemodynamic evaluation in baseline and isovolumic conditions and collected LV samples for histological and molecular analysis. Results: Preconditioning with exercise was capable to restore LV systolic and diastolic dysfunction in both baseline and isovolumic conditions (P < .05). This improved was paralleled with prevention of LV cardiomyocytes atrophy, fibrosis, and endothelin 1 mRNA levels (P < .05). Conclusions: Our findings suggest that exercise preconditioning can prevent LV dysfunction secondary to MCT-induced PAH, which is of particular interest for the familial form of the disease that is manifested by greater severity or earlier onset.

O Treinamento Físico Resistido Atenua as Disfunções Ventriculares Esquerdas em Modelo de Hipertensão Arterial Pulmonar

“…22 Em relação à HAP, intervenções combinadas de exercícios, incluindo aeróbicos, treinamento de resistência e treinamento muscular inspiratório específico, demonstraram ser seguras para esses pacientes e resultaram em melhorias significativas na potência muscular, na capacidade de exercício e na sobrevida. [23][24][25] Apesar disso, embora o exercício aeróbico tenha demonstrado evitar a disfunção diastólica e sistólica do ventrículo esquerdo nas condições de linha de base e isovolumétrica, 26 na HAP induzida por MCT, o impacto do TFR na disfunção do ventrículo esquerdo nesse modelo é desconhecido.…”

Training programs in preclinical studies. The example of pulmonary hypertension. Systematic review and meta-analysis

“…Mechanisms underlying such exerciseinduced protection can be related to the prevention of mitochondrial damage, fibrosis, decreased oxidative capacity, inflammation or neurohumoral activation. A more detailed summary of the expected advantages of exercise training, which were observed in a number of experimental models of PH, and their mechanistic background, is provided in Table 1 [13][14][15][16][17][18][19][20][21]. Table 2 summarizes the major findings from existing preclinical studies in relation to clinical ones [1,22] with an emphasis on the settings of training programs adopted to PH subjects, their beneficial effects on exercise tolerance and disease development as well as major determinants of study outcomes.…”

Combined physical training protects the left ventricle from structural and functional damages in experimental pulmonary arterial hypertension

“…These changes weaken their LV function as it influences LV segmental function and torsion and decreases the systolic volume and thus their capacity to tolerate physical effort [ 3 , 4 ]. In experimental PAH induced by MCT the LV presents reduced mass and cell dimensions [ 5 , 8 , 16 ] along with increased collagen and fibrosis [ 19 – 21 ]. Such structural changes lead to LV contractile dysfunctions characterized by reduced ejection fraction and fractional shortening and impaired LV myocyte Ca 2+ cycling and contractility (i.e., reduced amplitude of contraction and prolonged contraction and relaxation velocities) [ 20 – 23 ].…”