Inspiratory Muscle Weakness in Diastolic Dysfunction.

Lavietes, M H; Gerula, C M; Fless, K G; Cherniack, N S; Arora, R R.

doi:10.1097/01823246-200415040-00014

Cited by 7 publications

(13 citation statements)

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“…This was observed for both the HIIT and MCT exercise training regimens, which indicates an apparent metabolic inflexibility of the diaphragm in HFpEF—a finding that opposes previous data where exercise training as primary prevention was beneficial in the period preceding the development of HFpEF . As such, these data may have important clinical implications for treating respiratory muscle weakness in patients with HFpEF, suggesting that alternative therapeutic interventions may provide greater benefits compared with aerobic exercise training. Nevertheless, the finding that both training regimens still improved exercise capacity in HFpEF supports the current notion that exercise training is an effective treatment strategy for the HFpEF syndrome …”

Section: Discussioncontrasting

confidence: 59%

“…Recent data indicate that respiratory muscle weakness is present in patients with HFpEF. Noninvasive functional measures are reduced compared with age‐matched controls and these are correlated to exercise intolerance, increased sensations of breathless, and an elevated respiratory drive . Our laboratory recently confirmed these studies with direct evidence, where a hypertensive rat model of HFpEF demonstrated diaphragm contractile dysfunction that was linked to mitochondrial complex I functional impairments, fiber atrophy, and a fiber type shift from a glycolytic towards an oxidative phenotype .…”

Section: Introductionmentioning

confidence: 60%

“…In contrast to HFrEF, the effects of HFpEF on the diaphragm remain relatively unknown attributable, in part, to this patient cohort only more recently becoming apparent and the lack of appropriate animal models. Nevertheless, current evidence suggests that diaphragm weakness is an important driving factor that exacerbates the main symptom of exercise intolerance in patients with HFpEF . While the underlying intracellular mechanisms responsible for diaphragm dysfunction in HFpEF remain poorly explored, our laboratory recently provided initial evidence using a hypertensive rat model of HFpEF .…”

Section: Discussionmentioning

confidence: 99%

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Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction

Bowen

Brauer

Rolim

et al. 2017

JAHA

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BackgroundRespiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments.Methods and ResultsObese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high‐intensity interval training (n=11), or moderate‐continuous training (n=11). Obese rats developed an obvious HFpEF phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28 weeks, neither the exercise training regimen of high‐intensity interval training or moderate‐continuous training reversed any of the diaphragm alterations induced by HFpEF.ConclusionsThis study, using a well‐characterized rat model of HFpEF underpinned by multiple comorbidities and exercise intolerance (ie, one that closely resembles the patient phenotype), provides evidence that diaphragm alterations and dysfunction induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in HFpEF warrants further investigation.

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Section: Discussioncontrasting

confidence: 59%

Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction

Bowen

Brauer

Rolim

et al. 2017

JAHA

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“…In other studies, a slow‐to‐fast switch was also observed in the lower limb muscles of patients with CHF (Lipkin et al, ; Mancini et al, ; Sullivan et al, ), together with reduced muscle oxidative metabolism (Sullivan et al, ). Inspiratory muscle weakness, as measured by reduced maximal inspiratory pressure, was also shown in patients with diastolic dysfunction (Lavietes et al, ). Interestingly, exercise training induced several beneficial effects in patients with CHF as demonstrated by the reduction in systemic (Gielen et al, ) and local (lower limb muscles) inflammation (Gielen et al, ) and proteolytic markers (Gielen et al, ) as well as improvements in muscle mitochondrial oxidative capacity (Gielen et al, ).…”

mentioning

confidence: 97%

Therapeutic Approaches in Mitochondrial Dysfunction, Proteolysis, and Structural Alterations of Diaphragm and Gastrocnemius in Rats With Chronic Heart Failure

et al. 2015

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Patients with chronic heart failure (CHF) experience exercise intolerance, fatigue and muscle wasting, which negatively influence their survival. We hypothesized that treatment with either the antioxidant N-acetyl cysteine (NAC) or the proteasome inhibitor bortezomib of rats with monocrotaline-induced CHF may restore inspiratory and limb muscle mass, function, and structure through several molecular mechanisms involved in protein breakdown and metabolism in the diaphragm and gastrocnemius. In these muscles of CHF-cachectic rats with and without treatment with NAC or bortezomib (N = 10/group) and non-cachectic controls, proteolysis (tyrosine release, proteasome activities, ubiquitin-proteasome markers), oxidative stress, inflammation, mitochondrial function, myosin, NF-κB transcriptional activity, muscle structural abnormalities, and fiber morphometry were analyzed together with muscle and cardiac functions. In diaphragm and gastrocnemius of CHF-cachectic rats, tyrosine release, proteasome activity, protein ubiquitination, atrogin-1, MURF-1, NF-κB activity, oxidative stress, inflammation, and structural abnormalities were increased, while muscle and cardiac functions, myosin content, slow- and fast-twitch fiber sizes, and mitochondrial activity were decreased. Concomitant treatment of CHF-cachectic rats with NAC or bortezomib improved protein catabolism, oxidative stress, inflammation, muscle fiber sizes, function and damage, superoxide dismutase and myosin levels, mitochondrial function (complex I, gastrocnemius), cardiac function and decreased NF-κB transcriptional activity in both muscles. Treatment of CHF-cachectic animals with NAC or bortezomib attenuated the functional (heart, muscles), biological, and structural alterations in muscles. Nonetheless, future studies conducted in actual clinical settings are warranted in order to assess the potential beneficial effects and safety concerns of these pharmacological agents on muscle mass loss and wasting in CHF-cachectic patients.

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“…However, this hypothesis seems less probable, since patients with dyspnoea exhibited no significant differences in LV functional parameters in comparison to those without breathlessness. On the other hand, it might not be possible to reject this latter hypothesis since patients with dyspnoea, by presenting increased LV mass, could be more sensitive to hemodynamic changes in the pulmonary territory and thus develop breathlessness (Lavietes et al. 2004, Mottram et al.…”

Section: Discussionmentioning

confidence: 99%