Endothelial progenitor cell mobilization based on exercise volume in patients with cardiovascular disease and healthy individuals: a systematic review and meta-analysis.

Endothelial progenitor cells (EPCs) play a vital role in protecting endothelial dysfunction and cardiovascular disease (CVD). Physical exercise stimulates the mobilization of EPCs, and along with vascular endothelial growth factor (VEGF), promotes EPC differentiation, and contributes to vasculogenesis. The present meta-analysis examines the exercise-induced EPC mobilization and has an impact on VEGF in patients with CVD and healthy individuals. Database research was conducted (PubMed, EMBASE, Cochrane Library of Controlled Trials) by using an appropriate algorithm to indicate the exercise-induced EPC mobilization studies. Eligibility criteria included EPC measurements following exercise in patients with CVD and healthy individuals. A continuous random effect model meta-analysis (PROSPERO-CRD42019128122) was used to calculate mean differences in EPCs (between baseline and post-exercise values or between an experimental and control group). A total of 1460 participants (36 studies) were identified. Data are presented as standard mean difference (Std.MD) and 95% confidence interval (95% CI). Aerobic training stimulates the mobilization of EPCs and increases VEGF in patients with CVD (EPCs: Std.MD: 1.23, 95% CI: 0.70-1.76; VEGF: Std.MD: 0.76, 95% CI:0.16-1.35) and healthy individuals (EPCs: Std.MD: 1.11, 95% CI:0.53-1.69; VEGF: Std.MD: 0.75, 95% CI: 0.01-1.48). Acute aerobic exercise (Std.MD: 1.40, 95% CI: 1.00-1.80) and resistance exercise (Std.MD: 0.46, 95%CI: 0.10-0.82) enhance EPC numbers in healthy individuals. Combined aerobic and resistance training increases EPC mobilization (Std.MD:1.84, 95% CI: 1.03-2.64) in patients with CVD. Adequate exercise volume (>60%VO2max >30 min; P = 0.00001) yields desirable results. Our meta-analysis supports the findings of the literature. Exercise volume is required to obtain clinically significant results. Continuous exercise training of high-to-moderate intensity with adequate duration as well as combined training with aerobic and resistance exercise stimulates EPC mobilization and increases VEGF in patients with CVD and healthy individuals.

A Cardiac Rehabilitation Program Increases the Acute Response of Endothelial Progenitor Cells to Maximal Exercise in Heart Failure Patients.

Purpose: The purpose of this study was to investigate the effect of a cardiac rehabilitation program on the acute response on endothelial progenitor cells and circulating endothelial cells after maximal exercise in patients with chronic heart failure of different severity. Methods: Forty-four chronic heart failure patients were enrolled in a 36-session cardiac rehabilitation program. All patients underwent an initial maximal cardiopulmonary exercise test before and a final maximal cardiopulmonary exercise test after the cardiac rehabilitation program. The patients were divided in two groups of severity according to the median value of peak VO2. Blood was collected at 4 time points; 2 time points at rest, and 2 time points after each cardiopulmonary exercise test. Five endothelial cellular populations were quantified by flow cytometry. Results: Although there was a higher increase in the mobilization of subgroups of endothelial progenitor cells and circulating endothelial cells after the final cardiopulmonary exercise test compared to the initial test within each severity group (p < 0.05), no significant differences between severity groups were observed (p > 0.05). Conclusions: A 36-session cardiac rehabilitation program had similar beneficial effects on the acute response of endothelial progenitor cells and circulating endothelial cells after maximal exercise in patients with chronic heart failure of different severity.

Acute Cardiorespiratory Responses to Different Exercise Modalities in Chronic Heart Failure Patients-A Pilot Study.

The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO2peak intensities between three "iso-work" protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON70) and (c) a lower intensity continuous protocol (CON50) in patients with chronic heart failure (CHF). Ten male CHF patients (aged 55.1 ± 16.2 years) performed in separate days a single session of a HIIT protocol consisted of 4 sets × 4 min cycling at 80% VO2peak with 3 min of recovery at 50% VO2peak, a CON70 protocol corresponding to 70% VO2peak and a CON50 protocol corresponding to 50% VO2peak. Cardiopulmonary data were collected by an online gas analysis system. The HIIT and CON70 elicited higher cardiorespiratory responses compared to CON50 with no differences between them (p > 0.05). In HIIT and CON70, patients exercised longer at >80% and >90% VO2peak. The completion rate was 100% for the three protocols. Not any adverse events were observed in either protocol. Both HIIT and CON70 elicited a stronger physiological stimulus and required shorter time than CON50. Both HIIT and CON70 also induced comparable hemodynamic responses and ventilatory demand.

The acute and long-term effects of a cardiac rehabilitation program on endothelial progenitor cells in chronic heart failure patients: Comparing two different exercise training protocols.

BACKGROUND: Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are also impaired. The purpose of the study was to assess the effect of a cardiac rehabilitation (CR) program on the increase of EPCs at rest and on the acute response after maximal exercise in patients with CHF and investigate whether there were differences between two exercise training protocols and patients of NYHA II and III classes. METHODS: Forty-four patients with stable CHF enrolled in a 36-session CR program and were randomized in one training protocol; either high-intensity interval training (HIIT) or HIIT combined with muscle strength (COM). All patients underwent maximum cardiopulmonary exercise testing (CPET) before and after the CR program and venous blood was drawn before and after each CPET. Five endothelial cellular populations, expressed as cells/106 enucleated cells, were quantified by flow cytometry. RESULTS: An increase in all endothelial cellular populations at rest was observed after the CR program (p < 0.01). The acute response after maximum exercise increased in 4 out of 5 endothelial cellular populations after rehabilitation. Although there was increase in EPCs at rest and the acute response after rehabilitation in each exercise training group and each NYHA class, there were no differences between HIIT and COM groups or NYHA II and NYHA III classes (p > 0.05). CONCLUSIONS: A 36-session CR program increases the acute response after maximum CPET and stimulates the long-term mobilization of EPCs at rest in patients with CHF. These benefits seem to be similar between HIIT and COM exercise training protocols and between patients of different functional classes.

Long term follow-up of quality of life and functional ability in patients with ICU acquired Weakness - A post hoc analysis.

PURPOSE: ICU acquired Weakness (ICUaW) is a common complication of critical illness. The aim of our study was the assessment of quality of life (QoL) and functional ability of patients with ICUaW, 6 months post hospital discharge. MATERIAL AND METHODS: Eight hundred seventy eight consecutive patients who had been discharged from the ICU were evaluated and 128 of them, 36 with ICUaW, were eligible for the study. Muscle strength was evaluated with MRC and Hand grip dynamometry. The Functional Independence Measure (FIM) was used to evaluate the functional ability while QoL was assessed with the Nottingham Health Profile and with the SF-36 questionnaire. RESULTS: Patients with ICUaW continued to have low MRC at hospital discharge, [53(49-56) vs. 59(58-60), p < 0.05]. Patients who developed ICUaW had lower Hand grip dynamometry at ICU, hospital discharge and 6 months after (p < 0.05). Patients with ICUaW have significantly lower FIM score at hospital discharge, 3 and 6 months post hospital discharge (p < 0.05) and persistently lower QoL at 3 and 6 months post hospital discharge(p < 0.05). CONCLUSIONS: ICUaW is associated with persistent deficiencies in functional ability and Qol leading to a prolonged period of recovery. Further research is needed in the field of prevention and targeted rehabilitation of functionality in this patient group.

Effect of neuromuscular stimulation and individualized rehabilitation on muscle strength in Intensive Care Unit survivors: A randomized trial.

PURPOSE: Intensive Care Unit (ICU) survivors experience muscle weakness leading to restrictions in functional ability. Neuromuscular electrical stimulation (NMES) has been an alternative to exercise in critically ill patients. The aim of our study was to investigate its effects along with individualized rehabilitation on muscle strength of ICU survivors. MATERIAL AND METHODS: Following ICU discharge, 128 patients (age: 53±16years) were randomly assigned to daily NMES sessions and individualized rehabilitation (NMES group) or to control group. Muscle strength was assessed by the Medical Research Council (MRC) score and hand grip at hospital discharge. Secondary outcomes were functional ability and hospital length of stay. RESULTS: MRC, handgrip, functional status and hospital length of stay did not differ at hospital discharge between groups (p>0.05). ΔMRC% one and two weeks after ICU discharge tended to be higher in NMES group, while it was significant higher in NMES group of patients with ICU-acquired weakness at two weeks (p=0.05). CONCLUSIONS: NMES and personalized physiotherapy in ICU survivors did not result in greater improvement of muscle strength and functional status at hospital discharge. However, in patients with ICU-aw NMES may be effective. The potential benefits of rehabilitation strategies should be explored in larger number of patients in future studies. CLINICAL TRIAL REGISTRATION: www.Clinicaltrials.gov: NCT01717833.

Neuromuscular electrical stimulation acutely mobilizes endothelial progenitor cells in critically ill patients with sepsis.

BACKGROUND: Endothelial progenitor cells (EPCs) have been suggested to constitute a restoration index of the disturbed endothelium in ICU patients. Neuromuscular electric stimulation (NMES) is increasingly employed in ICU to prevent comorbidities such as ICU-acquired weakness, which is related to endothelial dysfunction. The role of NMES to mobilize EPCs has not been investigated yet. The purpose of this study was to explore the NMES-induced effects on mobilization of EPCs in septic ICU patients. METHODS: Thirty-two septic mechanically ventilated patients (mean ± SD, age 58 ± 14 years) were randomized to one of the two 30-min NMES protocols of different characteristics: a high-frequency (75 Hz, 6 s on-21 s off) or a medium-frequency (45 Hz, 5 s on-12 s off) protocol both applied at maximally tolerated intensity. Blood was sampled before and immediately after the NMES sessions. Different EPCs subpopulations were quantified by cytometry markers CD34(+)/CD133(+)/CD45(-), CD34(+)/CD133(+)/CD45(-)/VEGFR2 (+) and CD34(+)/CD45(-)/VEGFR2 (+). RESULTS: Overall, CD34(+)/CD133(+)/CD45(-) EPCs increased from 13.5 ± 10.2 to 20.8 ± 16.9 and CD34(+)/CD133(+)/CD45(-)/VEGFR2 (+) EPCs from 3.8 ± 5.2 to 6.4 ± 8.5 cells/10(6) enucleated cells (mean ± SD, p < 0.05). CD34(+)/CD45(-)/VEGFR2 (+) EPCs also increased from 16.5 ± 14.5 to 23.8 ± 19.2 cells/10(6) enucleated cells (mean ± SD, p < 0.05). EPCs mobilization was not affected by NMES protocol and sepsis severity (p > 0.05), while it was related to corticosteroids administration (p < 0.05). CONCLUSIONS: NMES acutely mobilized endothelial progenitor cells, measures of the endothelial restoration potential, in septic ICU patients.

Acute microcirculatory effects of medium frequency versus high frequency neuromuscular electrical stimulation in critically ill patients - a pilot study.

BACKGROUND: Intensive care unit-acquired weakness (ICUAW) is a common complication, associated with significant morbidity. Neuromuscular electrical stimulation (NMES) has shown promise for prevention. NMES acutely affects skeletal muscle microcirculation; such effects could mediate the favorable outcomes. However, optimal current characteristics have not been defined. This study aimed to compare the effects on muscle microcirculation of a single NMES session using medium and high frequency currents. METHODS: ICU patients with systemic inflammatory response syndrome (SIRS) or sepsis of three to five days duration and patients with ICUAW were studied. A single 30-minute NMES session was applied to the lower limbs bilaterally using current of increasing intensity. Patients were randomly assigned to either the HF (75 Hz, pulse 400 µs, cycle 5 seconds on - 21 seconds off) or the MF (45 Hz, pulse 400 µs, cycle 5 seconds on - 12 seconds off) protocol. Peripheral microcirculation was monitored at the thenar eminence using near-infrared spectroscopy (NIRS) to obtain tissue O2 saturation (StO2); a vascular occlusion test was applied before and after the session. Local microcirculation of the vastus lateralis was also monitored using NIRS. RESULTS: Thirty-one patients were randomized. In the HF protocol (17 patients), peripheral microcirculatory parameters were: thenar O2 consumption rate (%/minute) from 8.6 ± 2.2 to 9.9 ± 5.1 (P = 0.08), endothelial reactivity (%/second) from 2.7 ± 1.4 to 3.2 ± 1.9 (P = 0.04), vascular reserve (seconds) from 160 ± 55 to 145 ± 49 (P = 0.03). In the MF protocol: thenar O2 consumption rate (%/minute) from 8.8 ± 3.8 to 9.9 ± 3.6 (P = 0.07), endothelial reactivity (%/second) from 2.5 ± 1.4 to 3.1 ± 1.7 (P = 0.03), vascular reserve (seconds) from 163 ± 37 to 144 ± 33 (P = 0.001). Both protocols showed a similar effect. In the vastus lateralis, average muscle O2 consumption rate was 61 ± 9%/minute during the HF protocol versus 69 ± 23%/minute during the MF protocol (P = 0.5). The minimum amplitude in StO2 was 5 ± 4 units with the HF protocol versus 7 ± 4 units with the MF protocol (P = 0.3). Post-exercise, StO2 increased by 6 ± 7 units with the HF protocol versus 5 ± 4 units with the MF protocol (P = 0.6). These changes correlated well with contraction strength. CONCLUSIONS: A single NMES session affected local and systemic skeletal muscle microcirculation. Medium and high frequency currents were equally effective.

Electrical muscle stimulation: an effective form of exercise and early mobilization to preserve muscle strength in critically ill patients.

Purpose. This is a secondary analysis of previously published data to investigate the effects of electrical muscle stimulation (EMS) on strength of various muscle groups in critically ill patients. Methods. One hundred forty-two consecutive patients, with APACHE II score ≥ 13, were randomly assigned to the EMS or the control group. EMS sessions were applied daily on vastus lateralis, vastus medialis, and peroneus longus of both lower extremities. Various muscle groups were evaluated with the Medical Research Council (MRC) scale for muscle strength. Handgrip strength assessment was also employed. Results. Twenty four patients in the EMS group and 28 patients in the control group were finally evaluated. EMS patients achieved higher MRC scores than controls (P ≤ 0.05) in wrist flexion, hip flexion, knee extension, and ankle dorsiflexion. Collectively, the EMS group performed higher (P < 0.01) in the legs and overall. Handgrip strength correlated (P ≤ 0.01) with the upper and lower extremities' muscle strength and the overall MRC scores. Conclusions. EMS has beneficial effects on the strength of critically ill patients mainly affecting muscle groups stimulated, while it may also affect muscle groups not involved presenting itself as a potential effective means of muscle strength preservation and early mobilization in this patient population.