Early Phase II Comprehensive Cardiac Rehabilitation after Acute Myocardial Infarction.

BACKGROUND: Cardiac rehabilitation is beneficial for patients after ST-segment elevation myocardial infarction (STEMI). However, most institutes perform outpatient training phase (phase II) of post-MI cardiac rehabilitation after 2-4 weeks. To evaluate the possibility of performing cardiac rehabilitation with an earlier schedule after STEMI. METHODS: We conducted a series of early phase II cardiac rehabilitation starting from 5-7 days after STEMI, including the training group (n = 28) and the control group (n = 42). RESULTS: The results showed an improved mental component summary of the SF-36 questionnaire after 6 months in the training group. No adverse event was noticed during this early phase II training. CONCLUSIONS: Cardiac rehabilitation after STEMI might be started earlier than previously thought for clinical use or further research.

Analysis of Exercise Capacity of Children with Kawasaki Disease by a Coronary Artery z Score Model (ZSP Version 4) Derived by the Lambda-Mu-Sigma Method.

OBJECTIVE: To compare exercise capacity measured by direct cardiopulmonary exercise testing (CPET) of children with Kawasaki disease with different coronary artery diameter z scores (CA z score). STUDY DESIGN: This was a retrospective study that recruited children with Kawasaki disease after the acute stage receiving CPETs determined by CPET with treadmill. CA z score was based on a model using the Lambda-Mu-Sigma method. Max-Z was defined as the maximum z score of the proximal left anterior descending CA (LCA) or right CA (RCA). Children with Kawasaki disease with a Max z <2.0 and ≥2.0 were defined as Kawasaki disease group 1 and Kawasaki disease group 2, respectively. RESULTS: We recruited 32 boys and 17 girls with a mean age of 12.39 ± 3.61 years. Kawasaki disease group 1 (n = 36) had significantly higher peak metabolic equivalent (peak-MET) and peak rate pressure product (PRPP) than Kawasaki disease group 2 (n-13) (P = .046, P < .001). Max-Z correlated with peak-MET moderately and negatively (P < .001, Spearman rho= - .506). Max-Z correlated with PRPP modestly and negatively (P = .011, Spearman rho= - .360). CONCLUSIONS: Children after Kawasaki disease with a coronary artery Max-Z ≥ 2.0 had significantly lower peak exercise capacity than those with a Max-Z < 2.0. Max-Z might be used as an indicator of CA reserve and exercise capacity during peak exercise after the acute stage of Kawasaki disease.

Exercise Training Alleviates Hypoxia-induced Mitochondrial Dysfunction in the Lymphocytes of Sedentary Males.

This study elucidates how interval and continuous exercise regimens affect the mitochondrial functionality of lymphocytes under hypoxic stress. Sixty healthy sedentary males were randomly assigned to engage in either high-intensity interval training (HIIT, 3 min intervals at 80% and 40% VO2max, n = 20) or moderate-intensity continuous training (MICT, sustained 60% VO2max, n = 20) for 30 min/day, 5 days/week for 6 weeks or were assigned to a control group that did not receive exercise intervention (n = 20). Lymphocyte phenotypes/mitochondrial functionality under hypoxic exercise (HE, 100 W under 12% O2) were determined before and after the various interventions. Before the intervention, HE (i) increased the mobilization of senescent (CD57+/CD28-) lymphocytes into the blood, (ii) decreased the ATP-linked O2 consumption rate (OCR), the reserve capacity of OCR, and the citrate synthase activity in the mitochondria, and (iii) lowered the mitochondrial membrane potential (MP) and elevated the matrix oxidant burden (MOB) of lymphocytes. However, both HIIT and MICT significantly (i) decreased blood senescent lymphocyte counts, (ii) enhanced the mitochondrial OCR with increased citrate synthase and succinate dehydrogenase activities, (iii) increased mitochondrial MP and decreased MOB and (iv) increased the ratio of mitofusin to DRP-1 in lymphocytes after HE. Thus, we concluded that either HIIT or MICT effectively improves lymphocyte mitochondrial functionality by enhancing oxidative phosphorylation and suppressing oxidative damage under hypoxic conditions.

Comparison of cardiac autonomic nervous system disturbed by sleep deprivation in sex and menstrual phase.

Sleep deprivation (SD) leads to cardiovascular risk by disturbing autonomic nervous system (ANS). Whether sex or menstrual cycle influences cardiac ANS interfered by SD remained unclear. This investigation was to further clarify the effects of different menstrual phases on cardiac autonomic nervous activity disturbed by SD. Methodologically, cardiac autonomic modulation before and after 30 h of total SD was determined by spectral analysis of heart rate variability in 10 healthy females during the mid-follicular (FF) and mid-luteal (FL) phases and 10 healthy males. The result showed that before SD, the FF subjects, but not FL, had higher normalized high frequency (nHF) (vagal activity) or lower ratio of low frequency (LF) to high frequency(HF) power (sympathetic activity) while performing deep breathing or Valsalva maneuver (40 mmHg) than the male subjects did. However, the SD for 30 h in the FF group significantly increased the LF/HF ratio and decreased nHF level at rest and in responses to deep breathing and Valsalva maneuver, despite no significant change of HRV in either male or FL group. Simultaneously, the SD substantially lowered venous PCO2 in the FF group, and the decreased PCO2 level was associated with the increased LF/HF ratio following SD. We concluded that 30-h acute SD promotes sympathetic and depresses [corrected] parasympathetic activities in female during the follicular phase rather than the luteal phase. Compared to FF, SD-triggered cardiac sympathetic activation is blunted in FL. The study provides further insight into the physiology of acute SD in different sex and menstrual phases.

Activation of lymphocyte autophagy/apoptosis reflects haemodynamic inefficiency and functional aerobic impairment in patients with heart failure.

Lymphocytopenia is associated with an adverse prognosis in heart failure (HF). The present study investigated whether lymphocytopenia results from activated lymphocyte autophagy/apoptosis, which reflects haemodynamic inefficiency and functional aerobic impairment in patients with HF. One hundred and twenty-seven patients with HF were divided into three groups: HF with non- (lymphocytes ≥2000 cells/µl; n=45), mild (lymphocytes between ≥1500 cells/µl and <2000 cells/µl; n=39) and severe (lymphocytes <1500 cells/µl; n=43) lymphocytopenia. Lymphocyte autophagy/apoptosis, ventilatory/haemodynamic efficiencies and generic/disease-specific quality of life were analysed in these patients with HF and 35 normal counterparts. The results demonstrated that patients with HF with severe lymphocytopenia had (i) increased G-protein-coupled receptor kinase-2 (GRK-2) levels, (ii) lower mammalian target of rapamycin (mTOR) levels with higher lysosome-associated membrane protein-2 (LAMP-2) expression and Acridine Orange (AO) staining, (iii) lower mitochondrial transmembrane potential with higher caspase-3 activation and phosphatidylserine (PS) exposure, and (iv) greater extents of adrenaline (epinephrine)-induced apoptosis in lymphocytes, and higher plasma noradrenaline (norepinephrine)/adrenaline, myeloperoxidase and interleukin-6 concentrations than patients with HF without lymphocytopenia and normal counterparts did. Moreover, lymphocyte caspase-3 activation was an effect modifier, which modulated the correlation status between lymphocyte count and GRK-2 level. Lymphocyte count was positively correlated with peak cardiac output and peak oxygen consumption (VO2peak) in patients with HF. In addition, HF with lymphocytopenia was accompanied by lower Short Form-36 physical/mental component scores and increased Minnesota Living with Heart Failure Questionnaire scores. Therefore, we conclude that increased sympathetic activation and oxidative stress/pro-inflammatory status cause lymphocytopenia by activating programmed lymphocyte death in patients with HF. Moreover, a low lymphocyte count correlates with reduced haemodynamics and aerobic capacity, which reflects poor generic/disease-specific quality of life in patients with HF.

Hypoxic exercise training improves cardiac/muscular hemodynamics and is associated with modulated circulating progenitor cells in sedentary men.

BACKGROUND: Circulating progenitor cells (CPCs) improve cardiovascular function and organ perfusion by enhancing the capacities of endothelial repair and neovasculogenesis. This study investigates whether exercise regimens with/without hypoxia affect cardiac and muscular hemodynamics by modulating CPCs and angiogenic factors. METHODS: Forty sedentary males were randomly divided into hypoxic (HT, n=20) and normoxic (NT, n=20) training groups. The subjects were trained on a bicycle ergometer at 60%VO(2max) under 15% (HT) or 21% (NT) O2 conditions for 30 min daily, five days weekly for five weeks. RESULTS: After the five-week interventions, the HT group exhibited a larger improvement in aerobic capacity than the NT group. Furthermore, the HT regimen (i) enhanced cardiac output (Q(H)) and perfusion (Q(M))/oxygenation of vastus lateralis during exercise; (ii) increased levels of CD34(+)/KDR(+)/CD117(+), CD34(+)/KDR(+)/CD133(+), and CD34(+)/KDR(+)/CD31(+) cells in blood; (iii) promoted the proliferative capacity of these CPC subsets, and (iv) elevated plasma nitrite/nitrate, stromal cell-derived factor-1 (SDF-1), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A) concentrations. Despite the lack of changes in Q(H) and the number or proliferative capacity of CD34(+)/KDR(+)/CD117(+) or CD34(+)/KDR(+)/CD31(+) cells, the NT regimen elevated both Q(M) and plasma nitrite/nitrate levels and suppressed the shedding of endothelial cells (CD34(-)/KDR(+)/phosphatidylserine(+) cells). CONCLUSIONS: The HT regimen improves cardiac and muscular hemodynamic adaptations, possibly by promoting the mobilization/function of CPCs and the production of angiogenic factors.

Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men.

Exercise is linked with the type/intensity-dependent adaptive immune responses, whereas hypoxic stress facilitates the programmed death of CD4 lymphocytes. This study investigated how high intensity-interval (HIT) and moderate intensity-continuous (MCT) exercise training influence hypoxia-induced apoptosis and autophagy of CD4 lymphocytes in sedentary men. Thirty healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n=10) or MCT (sustained 60%VO2max, n=10) for 30 minutes/day, 5 days/week for 5 weeks, or to a control group that did not received exercise intervention (CTL, n=10). CD4 lymphocyte apoptotic and autophagic responses to hypoxic exercise (HE, 100 W under 12%O2 for 30 minutes) were determined before and after various regimens. The results demonstrated that HIT exhibited higher enhancements of pulmonary ventilation, cardiac output, and VO2 at ventilatory threshold and peak performance than MCT did. Before the intervention, HE significantly down-regulated autophagy by decreased beclin-1, Atg-1, LC3-II, Atg-12, and LAMP-2 expressions and acridine orange staining, and simultaneously enhanced apoptosis by increased phospho-Bcl-2 and active caspase-9/-3 levels and phosphotidylserine exposure in CD4 lymphocytes. However, five weeks of HIT and MCT, but not CTL, reduced the extents of declined autophagy and potentiated apoptosis in CD4 lymphocytes caused by HE. Furthermore, both HIT and MCT regimens manifestly lowered plasma myeloperoxidase and interleukin-4 levels and elevated the ratio of interleukin-4 to interferon-γ at rest and following HE. Therefore, we conclude that HIT is superior to MCT for enhancing aerobic fitness. Moreover, either HIT or MCT effectively depresses apoptosis and promotes autophagy in CD4 lymphocytes and is accompanied by increased interleukin-4/interferon-γ ratio and decreased peroxide production during HE.

Hypoxic exercise training promotes antitumour cytotoxicity of natural killer cells in young men.

The cytotoxic functions of NKs (natural killer cells) are critical in enabling the immune system to cope efficiently with malignancy. In the present study, we compared how various exercise regimens without/with hypoxia influence phenotypic characteristics of NK subsets and cytotoxicity of NKs to NPCs (nasopharyngeal carcinoma cells). A total of 60 sedentary males were randomly divided into five groups. Each group (n=12) underwent one of five regimens: normoxic (21% O(2)) control (N-C), hypoxic (15% O(2)) control (H-C), normoxic exercise (50% maximal work rate under 21% O(2); N-E), hypoxic relative exercise (50% maximal heart rate reserve under 15% O2; H-RE) or hypoxic absolute exercise (50% maximal work rate under 15% O(2); H-AE) for 30 min/day, 5 days/week for 4 weeks. The results showed that hypoxic exercise regimens increased pulmonary ventilation and tissue oxygen utilization. Moreover, the H-RE regimen resulted in enhanced aerobic fitness at a less intensive training workload in the H-AE regimen. Before each regimen, strenuous exercise elevated NK perforin/granzyme B content and promoted cytotoxicity of NKs to NPCs. However, the percentage of NKs expressing homing (CD11a)/terminally differentiated (CD57)/inhibitory [KLRG1 (killer cell lectin-like receptor G1)] molecules that entered the bloodstream from peripheral tissues increased following this exercise. After 4 weeks, both the H-AE and H-RE regimens produced an up-regulated expression of memory (CD45RO)/activating (NKG2D) molecules and was accompanied by a decrease in CD57/KLRG1 levels on NKs at rest and after strenuous exercise. Furthermore, the two regimens increased resting and exercise NK perforin/granzyme B content and NK-induced phosphatidylserine exposure of NPCs. In contrast, no significant change in the phenotypic characteristics of blood NK subsets or NK-induced NPC apoptosis was observed in the N-C, H-C and N-E regimens. Therefore we conclude that 15% O(2) exercise training reduces terminally differentiated NK subsets and up-regulates the expression of activating molecules and cytotoxic granule proteins in NKs, thereby enhancing the capacity of anti-NPC cytotoxicity by NKs. These findings could help to determine effective hypoxic exercise regimens for improving individual aerobic capacity and simultaneously promoting the natural cytotoxicity of NKs.

Hypoxic exercise training reduces senescent T-lymphocyte subsets in blood.

The integration and control of systemic immune responses depends on the regulated trafficking of T-lymphocytes. This study elucidates how various exercises regimens with/without hypoxia affect phenotypic characteristics of T-lymphocyte subsets in blood. Fifty sedentary males were randomly divided into five groups. Each group (n=10) received one of five interventions: normoxic (21%O2) resting (N-C), hypoxic (15%O2) resting (H-C), normoxic exercise (50%W(max) under 21%O2, N-T), hypoxic-relative exercise (50% maximal heart rate reserve under 15%O2, H-RT), or hypoxic-absolute exercise (50%W(max) under 15%O2, H-AT) for 30 min/day, 5 days/week for 4 weeks. Before the intervention, strenuous exercise up to exhaustion increased the mobilization of CD3, CD4, CD8, or CD8(bright) lymphocytes expressing activated (CD11a) or senescent (KLRG1) molecules into the peripheral blood compartment. The H-AT for 4 weeks up-regulated co-stimulatory molecule CD28 expression and was accompanied by depressed KLRG1 level on CD3, CD4, CD8, or CD8(bright) lymphocytes at rest or following exercise. Simultaneously, this intervention increased interferon-γ (IFN-γ) level and unchanged interleukin-4 level, as well as, decreased myeloperoxidase (MPO) and interleukin-6 levels in plasma. However, no significant changes in resting and exercise-induced mobilizations of various T-lymphocyte subsets and productions of cytokines and MPO occurred following the N-C, H-C, N-T, and H-RT interventions. Therefore, we conclude that 4-week H-AT intervention reduced senescent T-lymphocyte subsets with increasing IFN-γ level in blood, which responses are accompanied by depressed oxidative stress and pro-inflammatory cytokine production. These findings can help to determine an effective hypoxic exercise regimen to minimize immune dysfunction by retarding T-lymphocyte senescence.