To date, no study has examined the effects of high-intensity interval training that incorporates alternating bouts of maximal or supramaximal intensity exercise with either rest or light intensity recovery periods. This form of training is receiving widespread attention and acceptance in many other chronic conditions (ie, cardiovascular disease,31 heart failure [HF],32,33 chronic obstructive pulmonary disease [COPD]34) due to the potentially superior health effects compared with traditional continuous, moderate intensity exercise. To date, only PAH-induced animal models have been used to study the effects of high-intensity interval training on functional and physiologic parameters. These initial studies indicate that interval training does not induce right ventricular inflammation or cardiomyocyte apoptosis but rather stimulates the upregulation of pulmonary endothelial nitric oxide synthase, reduces fibrosis, and improves metabolic profile in right ventricular myocardium.35 Future studies in patients with PAH will be required to test the efficacy and safety of this form of training.
In addition to altered pulmonary vascular function, patients with PAH show increased systemic endothelial dysfunction36 along with a variety of skeletal muscle abnormalities. These skeletal abnormalities include increased protein degradation, a decrease in the type I/type II fiber ratio, reduced capillarization, decreased oxidative enzyme activity, altered mitochondrial function, and impaired excitation-contraction coupling.37,38 The combination of these changes, along with skeletal muscle atrophy, results in skeletal muscle dysfunction, which if left untreated can lead to impaired physical function, a poor quality of life, and the loss of independence. The etiology of these abnormalities is unclear; however, systemic inflammation and the effect of proinflammatory cytokines are thought to be contributing factors.36
Because of the effects of PAH on skeletal muscle, a number of studies have examined the effects of adding resistance training to an aerobic training regimen.18–20 As recommended by the American Heart Association,39 most of these studies used a low-resistance, high-repetition protocol. Results from these studies show that such training protocols result in increases in
In patients with HF and COPD, resistance training has been shown to be effective in ameliorating skeletal muscle abnormalities and improving physical function and health-related quality of life. Studies in patients with HF have shown that moderate-intensity resistance training can improve peripheral vascular function45 and blood flow46 and increase strength,46–49 walk distance,47,48 and aerobic capacity.46,50,51 Patients with COPD, completing 12 wk of resistance training experienced increases in strength, muscle mass, and decreased levels of proinflammatory cytokines.52–54 Given these patients exhibit skeletal muscle abnormalities, impaired physical function, and a reduced health-related quality of life similar to that seen in patients with PAH, it is not unreasonable to hypothesize that resistance training may serve as an effective treatment option for patients with PAH. However, additional research is needed to confirm this hypothesis.
A hallmark consequence of PAH is a significant attenuation of inspiratory muscle strength and endurance,55,56 which provokes fatigue and dyspnea during activity,55,56 and has high prognostic utility.57 Inspiratory muscle training, performed using a small handheld device with adjustable inspiratory pressure threshold loads that prohibit inhalation until exceeding a set negative pressure, has been established to effectively improve respiratory muscle strength and endurance. Even when performed on its own, IMT promotes increases in functional capacity in patients with heart disease.58 The first study to examine the efficacy of IMT in improving functional status in patients with PAH was reported in 2015 by Saglam et al.21 Patients randomized to IMT, utilized the inspiratory device for 30 min/d, 7 d/wk, for 6 wk at 30% of maximal inspiratory pressure. At the end of the trial, 6MWT distance increased from 427 ± 98 m to 476 ± 90 m (P = .001) along with improvements in severity of fatigue and dyspnea, as well as maximal inspiratory and expiratory pressure, whereas the control group on optimized clinical management experienced no changes. The modulatory effects of IMT that contribute to these improvements are not well understood in patients with PAH. However, previous studies in patients with HF indicate that IMT can reduce the accumulation of inspiratory muscle metabolites that are partly responsible for an exaggerated sympathetic response that causes vasoconstriction and reduced peripheral blood flow,58,59 thus improving skeletal muscle perfusion and submaximal exercise capacity.60 Although studies are needed to identify if these mechanisms are responsible for the improvements seen in the study by Saglam et al, the findings support the rationale for the clinical adoption of IMT in patients with PAH.
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