Cardiac Rehabilitation and Endothelial Function

Lanza, Gaetano Antonio; Golino, Michele; Villano, Angelo; Lanza, Oreste; Lamendola, Priscilla; Fusco, Augusto; Leggio, Massimo

doi:10.3390/jcm9082487

Cited by 21 publications

(14 citation statements)

References 88 publications

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“…Of great importance is a multidisciplinary approach involving exercise, diet, and psychological support for the correction of cardiovascular risk factors [ 139 , 140 ]. Moreover, it is important to keep in mind that, although the exercise exerts beneficial effects on endothelial function as evidenced in acute myocardial infarction, CAD, and HF patients and contributes to the reduction of cardiovascular alterations [ 146 ], whether it actually translates into improved clinical outcomes in COVID-19 patients remains to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Exercise Training and Cardiac Rehabilitation in COVID-19 Patients with Cardiovascular Complications: State of Art

Calabrese

Garofano

Palumbo

et al. 2021

Life

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Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which are still under study. Cardiovascular sequelae of COVID-19 include heart failure, cardiomyopathy, acute coronary syndrome, arrhythmias, and venous thromboembolism. This article aims to collect scientific evidence by exploiting PubMed, Scopus, and Pedro databases to highlight the cardiovascular complications of COVID-19 and to define the physiotherapy treatment recommended for these patients. Exercise training (ET), an important part of cardiac rehabilitation, is a powerful tool in physiotherapy, capable of inducing significant changes in the cardiovascular system and functional in the recovery of endothelial dysfunction and for the containment of thromboembolic complications. In conclusion, due to the wide variety of possible exercise programs that can be obtained by combining intensity, duration, and speed in various ways, and by adjusting the program based on continuous patient monitoring, exercise training is well suited to the treatment of post-COVID patients with an impaired cardiovascular system of various degrees.

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Section: Discussionmentioning

confidence: 99%

Exercise Training and Cardiac Rehabilitation in COVID-19 Patients with Cardiovascular Complications: State of Art

Calabrese

Garofano

Palumbo

et al. 2021

Life

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“…Being posttranslational modifiers, they might act quickly and maintain blood flow. Exercise training during cardiovascular rehabilitation might also increase sirtuin activities [16,82], which might be beneficial in future hypoxic episodes. However, further experimentation is necessary to study the effect of SIRT1 activation in vivo, which is expected to (partly) compensate the downregulation of the SIRT1 capacity.…”

Section: Discussionmentioning

confidence: 99%

Impact of Short-Term Hypoxia on Sirtuins as Regulatory Elements in HUVECs

Pecher

Potthast

Versen‐Höynck

2020

JCM

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Background: Sirtuins (SIRT) are NAD+-dependent deacetylases that are involved in stress response, antioxidative defense, and longevity via posttranslational modifications. SIRT1 directly activates nitric oxide synthase (NOS). Aging is associated with a reduced sirtuin function and reduction of the cofactor NAD+. Age-related atherosclerosis and vascular diseases are linked to a compromised sirtuin function. Vascular events like stroke and cardiac infarction result in acute hypoxia, which can additionally impact sirtuins and thus the vascular function. This prompted us to study sirtuins in intact HUVECs, under acute, short-term hypoxic conditions. Methods: We measured intracellular sirtuin and NAD+ levels in HUVECs exposed to hypoxia (2% O₂) for 10–120 min, compared to normoxic controls. SIRT1, SIRT3, and SIRT4 were measured at the protein (Western Blot) and the transcript level (qRT-PCR), SIRT1 and SIRT3 at the enzyme level (fluorometrically), and NAD+ levels were measured spectrophotometrically. Results: We observed a reduction of SIRT1 and SIRT4 at the protein level, a downregulation of SIRT1 at the transcript level and increased NAD+ levels under hypoxia. SIRT3 was not affected by hypoxia. Conclusions: Downregulation of SIRT1 under hypoxia might reduce production of the reactive oxygen species (ROS) via the respiratory chain and inhibit the mitochondrial ATP-synthase, resulting in energy conservation. NOS might be impaired if SIRT1 is decreased. Increased NAD+ levels might compensate these effects. Hypoxic downregulation of SIRT4 might lead to mitochondrial uncoupling, hence endothelial dysfunction, and ADP/ATP-translocase 2 (ANT2)-inhibition. NAD+ upregulation might partly compensate this effect.

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“…Consequently, our preliminary findings deserve confirmation in preclinical studies and in robust clinical studies on a larger sample. Meanwhile, this interrelationship between endothelial barrier integrity and the functional limitations of the post-acute phase may suggest the usefulness of personalized strategies targeting and monitoring endothelial dysfunction [ 35 , 36 , 37 ], thus potentially contributing to reducing the increased cardiovascular risk of COVID-19 survivors [ 38 ]. A number of strategies directed against viral replication or systemic inflammation have been tested for COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients

Ambrosino

Parrella²,

Formisano

et al. 2022

JCM

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Background: Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors. Methods: 36 consecutive COVID-19 survivors underwent symptom-limited incremental CPET and assessment of endothelium-dependent flow-mediate dilation (FMD) according to standardized protocols. Results: A significantly higher FMD was documented in patients with a preserved, as compared to those with a reduced, exercise capacity (4.11% ± 2.08 vs. 2.54% ± 1.85, p = 0.048), confirmed in a multivariate analysis (β = 0.899, p = 0.038). In the overall study population, FMD values showed a significant Pearson’s correlation with two primary CPET parameters, namely ventilation/carbon dioxide production (VE/VCO2) slope (r = −0.371, p = 0.026) and end-tidal carbon dioxide tension (PETCO2) at peak (r = 0.439, p = 0.007). In multiple linear regressions, FMD was the only independent predictor of VE/VCO2 slope (β = −1.308, p = 0.029) and peak PETCO2 values (β = 0.779, p = 0.021). Accordingly, when stratifying our study population based on their ventilatory efficiency, patients with a ventilatory class III-IV (VE/VCO2 slope ≥ 36) exhibited significantly lower FMD values as compared to those with a ventilatory class I-II. Conclusions: The alteration of endothelial barrier properties in systemic and pulmonary circulation may represent a key pathogenic mechanism of the reduced CPET performance in COVID-19 survivors. Personalized pharmacological and rehabilitation strategies targeting endothelial function may represent an attractive therapeutic option.

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Cardiac Rehabilitation and Endothelial Function

Cited by 21 publications

References 88 publications

Exercise Training and Cardiac Rehabilitation in COVID-19 Patients with Cardiovascular Complications: State of Art

Exercise Training and Cardiac Rehabilitation in COVID-19 Patients with Cardiovascular Complications: State of Art

Impact of Short-Term Hypoxia on Sirtuins as Regulatory Elements in HUVECs

Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients

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