Shu-Chun Huang

Aerobic interval training improves oxygen uptake efficiency by enhancing cerebral and muscular hemodynamics in patients with heart failure

BACKGROUND Abnormal ventilatory/hemodynamic responses to exercise contribute to functional impairment in patients with heart failure (HF). This study investigates how interval and continuous exercise regimens influence functional capacity by modulating ventilatory efficiency and hemodynamic function in HF patients. METHODS Forty-five HF patients were randomized to perform either aerobic interval training (AIT; 3-minute intervals at 40% and 80% VO(2peak)) or moderate continuous training (MCT; sustained 60% VO()for 30 min/day, 3 days/week for 12 weeks, or to a control group that received general healthcare (GHC). A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics, whereas a near-infrared spectroscopy was employed to assess perfusion/O2 extraction in frontal cerebral lobe (∆[THb]FC/∆[HHb]FC) and vastus lateralis (∆[THb]VL/∆[HHb]VL), respectively. RESULTS Following the 12-week intervention, the AIT group exhibited higher oxygen uptake efficiency slope (OUES) and lower VE-VCO2 slope than the MCT and GHC groups. Furthermore, AIT, but not MCT, boosted cardiac output (CO) and increased ∆[THb]FC, ∆[THb]VL, and ∆[HHb]VL during exercise. In multivariate analyses, CO was the dominant predictor of VO(2peak). ∆[THb]FC and ∆[THb]VL, which modulated the correlation between CO and OUES, were significantly correlated with OUES. Simultaneously, ∆[THb]VL was the only factor significantly associated with VE-VCO2 slope. Additionally, AIT reduced plasma brain natriuretic peptide, myeloperoxidase, and interleukin-6 levels and increased the Short Form-36 physical/mental component scores and decreased the Minnesota Living with Heart Failure questionnaire score. CONCLUSIONS AIT effectively improves oxygen uptake efficiency by enhancing cerebral/muscular hemodynamics and suppresses oxidative stress/inflammation associated with cardiac dysfunction, and also promotes generic/disease-specific qualities of life in patients with HF.

Suppression of cerebral hemodynamics is associated with reduced functional capacity in patients with heart failure

This investigation elucidated the underlying mechanisms of functional impairments in patients with heart failure (HF) by simultaneously comparing cardiac-cerebral-muscle hemodynamic and ventilatory responses to exercise among HF patients with various functional capacities. One hundred one patients with HF [New York Heart Association HF functional class II (HF-II, n = 53) and functional class III (HF-III, n = 48) patients] and 71 normal subjects [older control (O-C, n = 39) and younger control (Y-C, n = 32) adults] performed an incremental exercise test using a bicycle ergometer. A recently developed noninvasive bioreactance device was adopted to measure cardiac hemodynamics, and near-infrared spectroscopy was employed to assess perfusions in the frontal cerebral lobe (Δ[THb](FC)) and vastus lateralis muscle (Δ[THb](VL)). The results demonstrated that the Y-C group had higher levels of cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise than the O-C group. Moreover, these cardiac/peripheral hemodynamic responses to exercise in HF-III group were smaller than those in both HF-II and O-C groups. Although the change of cardiac output caused by exercise was normalized, the amounts of blood distributed to frontal cerebral lobe and vastus lateralis muscle in the HF-III group significantly declined during exercise. The HF-III patients had lower oxygen-uptake efficiency slopes (OUES) and greater Ve-Vo(2) slopes than the HF-II patients and age-matched controls. However, neither hemodynamic nor ventilatory response to exercise differed significantly between the HF-II and O-C groups. Cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise were directly related to the OUES and Vo(2peak) and inversely related to the Ve-Vco(2) slope. Moreover, cardiac output or Δ[THb](FC) was an effect modifier, which modulated the correlation status between Δ[THb](VL) and Ve-Vco(2) slope. We concluded that the suppression of cerebral/muscle hemodynamics during exercise is associated with ventilatory abnormality, which reduces functional capacity in patients with HF.

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, 100W 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.

Passive Leg Raising Correlates with Future Exercise Capacity after Coronary Revascularization

Hemodynamic properties affected by the passive leg raise test (PLRT) reflect cardiac pumping efficiency. In the present study, we aimed to further explore whether PLRT predicts exercise intolerance/capacity following coronary revascularization. Following coronary bypass/percutaneous coronary intervention, 120 inpatients underwent a PLRT and a cardiopulmonary exercise test (CPET) 2–12 days during post-surgery hospitalization and 3–5 weeks after hospital discharge. The PLRT included head-up, leg raise, and supine rest postures. The end point of the first CPET during admission was the supra-ventilatory anaerobic threshold, whereas that during the second CPET in the outpatient stage was maximal performance. Bio-reactance-based non-invasive cardiac output monitoring was employed during PLRT to measure real-time stroke volume and cardiac output. A correlation matrix showed that stroke volume during leg raise (SVLR) during the first PLRT was positively correlated (R = 0.653) with the anaerobic threshold during the first CPET. When exercise intolerance was defined as an anaerobic threshold < 3 metabolic equivalents, SVLR / body weight had an area under curve value of 0.822, with sensitivity of 0.954, specificity of 0.593, and cut-off value of 1504·10-3mL/kg (positive predictive value 0.72; negative predictive value 0.92). Additionally, cardiac output during leg raise (COLR) during the first PLRT was related to peak oxygen consumption during the second CPET (R = 0.678). When poor aerobic fitness was defined as peak oxygen consumption < 5 metabolic equivalents, COLR / body weight had an area under curve value of 0.814, with sensitivity of 0.781, specificity of 0.773, and a cut-off value of 68.3 mL/min/kg (positive predictive value 0.83; negative predictive value 0.71). Therefore, we conclude that PLRT during hospitalization has a good screening and predictive power for exercise intolerance/capacity in inpatients and early outpatients following coronary revascularization, which has clinical significance.

Cerebral desaturation in heart failure: Potential prognostic value and physiologic basis

Cerebral tissue oxygen saturation (SctO2) reflects cerebral perfusion and tissue oxygen consumption, which decline in some patients with heart failure with reduced ejection fraction (HFrEF) or stroke, especially during exercise. Its physiologic basis and clinical significance remain unclear. We aimed to investigate the association of SctO2 with oxygen transport physiology and known prognostic factors during both rest and exercise in patients with HFrEF or stroke. Thirty-four HFrEF patients, 26 stroke patients, and 17 healthy controls performed an incremental cardiopulmonary exercise test using a bicycle ergometer. Integrated near-infrared spectroscopy and automatic gas analysis were used to measure cerebral tissue oxygenation and cardiac and ventilatory parameters. We found that SctO2 (rest; peak) were significantly lower in the HFrEF (66.3±13.3%; 63.4±13.8%,) than in the stroke (72.1±4.2%; 72.7±4.5%) and control (73.1±2.8%; 72±3.2%) groups. In the HFrEF group, SctO2 at rest (SctO2rest) and peak SctO2 (SctO2peak) were linearly correlated with brain natriuretic peptide (BNP), peak oxygen consumption (V˙O2peak), and oxygen uptake efficiency slope (r between -0.561 and 0.677, p < 0.001). Stepwise linear regression showed that SctO2rest was determined by partial pressure of end-tidal carbon dioxide at rest (PETCO2rest), hemoglobin, and mean arterial pressure at rest (MAPrest) (adjusted R = 0.681, p < 0.05), while SctO2peak was mainly affected by peak carbon dioxide production (V˙CO2peak) (adjusted R = 0.653, p < 0.05) in patients with HFrEF. In conclusion, the study delineates the relationship of cerebral saturation and parameters associated with oxygen delivery. Moreover, SctO2peak and SctO2rest are correlated with some well-recognized prognostic factors in HFrEF, suggesting its potential prognostic value.

Short-term intensive training attenuates the exercise-induced interaction of mono-1/2 cells and platelets after coronary bypass in cardiac patients

The interaction between platelets and monocytes plays a critical role in the pathogenesis and progression of cardiovascular diseases. This study investigated how short-term intensive training (SIT) influences monocyte subset characteristics and exercise-induced monocyte and platelet aggregates (MPAs) following elective coronary bypass (CABG) in cardiac patients. Forty-nine patients hospitalised for CABG were randomised into SIT (N=26) and conventional training (CT, N=23) groups. The SIT subjects underwent supervised aerobic training at 80~120 % of the ventilatory anaerobic threshold based on sub-maximal exercise tests performed 7 days post-CABG for 20 sessions with two sessions/day and 30 min/session, which were completed within four weeks after surgery. The CT subjects performed light-intensity conditioning exercise for ≤4 sessions. Resting and maximal exercise-mediated monocyte characteristics and MPA were determined before and following intervention. The SIT group had a larger improvement in ventilation efficiency and anaerobic threshold than the CT group; the SIT group exhibited larger reductions in blood monocyte subtypes 1 and 2 (Mono1 and 2) counts at rest than the CT group; the SIT group but not the CT group exhibited attenuated formation of Mono1/platelet hetero-aggregation (MPA1) and CD42b expression on Mono1/2 caused by strenuous exercise; and plasma levels of macrophage inflammatory protein-1β and soluble P-selectin showed similar trends as Mono1/2 and MPA1, respectively. In conclusion, SIT modestly improved aerobic capacity in patients following CABG. Moreover, SIT simultaneously ameliorated the CD42b expression of Mono1/2 cells and maximal exercise-induced MPA1, which may reduce the risk of inflammatory thrombosis.