Effects of Different Types of Exercise Training on Pulmonary Arterial Hypertension: A Systematic Review

Lena Waller, Karsten Krüger, Kerstin Conrad, Astrid Weiss, Katharina Alack, Lena Waller, Karsten Krüger, Kerstin Conrad, Astrid Weiss, Katharina Alack

Abstract

Pulmonary arterial hypertension (PAH) represents a chronic progressive disease characterized by high blood pressure in the pulmonary arteries leading to right heart failure. The disease has been a focus of medical research for many years due to its worse prognosis and limited treatment options. The aim of this study was to systematically assess the effects of different types of exercise interventions on PAH. Electronic databases were searched until July 2019. MEDLINE database was used as the predominant source for this paper. Studies with regards to chronic physical activity in adult PAH patients are compared on retrieving evidence on cellular, physiological, and psychological alterations in the PAH setting. Twenty human studies and 12 rat trials were identified. Amongst all studies, a total of 628 human subjects and 614 rats were examined. Regular physical activity affects the production of nitric oxygen and attenuates right ventricular hypertrophy. A combination of aerobic, anaerobic, and respiratory muscle training induces the strongest improvement in functional capacity indicated by an increase of 6 MWD and VO2peak. In human studies, an increase of quality of life was found. Exercise training has an overall positive effect on the physiological and psychological components of PAH. Consequently, PAH patients should be encouraged to take part in regular exercise training programs.

Keywords: exercise training; experimental models; human studies; pulmonary arterial hypertension.

Conflict of interest statement

The authors declare no conflicts of interests regarding the publication of this manuscript.

Figures

Figure 1
Figure 1
The multifactorial etiopathogenesis of PAH. The pathogenesis of PAH implicates several molecular and cellular factors such as an increased proliferation of SMCs and ECs in the tunica intima and media. Risk factors (e.g., drugs) and genetic factors (e.g., dysfunctions in BMPR2) are also discussed to be involved in pathogenesis. PAH is characterized by an increased PVR and mean PAP ≥ 20 mmHg at rest, progressively leading to right ventricular hypertrophy (RVH), further resulting in right heart failure, loss of functional capacity and premature death. BMPR2, bone morphogenetic protein receptor type II; EC, endothelial cell; HIV, human immunodeficiency viruses, QoL, quality of life; SMC, smooth muscle cells; PAP, pulmonary arterial pressure; PVR, pulmonary vascular resistance (↑ = increased; ↓ = decreased).
Figure 2
Figure 2
Flow chart of the study inclusion process. A total of 32 studies were finally included to be assessed in this review (modified according to Moher et al. [46]).
Figure 3
Figure 3
Scheme of exercise interventions in animal studies. The experimental PAH was induced by a monocrotaline (MCT) injection in all included animal studies. The MCT injections (red line) and training programs were scheduled for different time points to assess various effects of exercise training (ET). In all studies [42,45,74,75,79,80,81,82,83,84,85,86], an adaptation period, highlighted in grey, was provided for 1–5 weeks to familiarize the rats with the treadmill running and adjust a similar baseline level. The periods of the training interventions are marked in white boxes (modified according to Moreira-Gonçalves et al. [87]).

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