Angiogenesis Modulated by EPC Clinical Trial
Official title:
Effects of Aerobic Interval and Continuous Exercise Trainings on Cardiovascular Hemorheological Characteristics and Atherothrombosis/Angiogenesis-related Variables in Patients With Chronic Heart Failure
Heart failure (HF) is a major and increasingly common cardiovascular syndrome, and is the
end result of many cardiovascular disorders. It has been reported that HF patients with
pharmacological therapy often remain burdened by dyspnea and fatigue, diminished exercise
tolerance, reduced quality of life, recurrent hospitalizations, and early mortality. HF is
associated with neurohumoral changes as the body attempts to reverse the effect of reduced
cardiac output and organ perfusion. Persistent neurohumoral excitation, however, actually
results in deterioration of myocardial function with inflammatory response, end-organ
damage, and skeletal muscle derangement, which lead to worsened exercise capacity.
Physical training can have beneficial effects on neurohumoral, inflammatory, metabolic and
central hemodynamic responses, as well as on endothelial, skeletal muscle and cardiovascular
function, leading to improvement in functional capacity and quality of life. All these
training-induced changes can effectively counteract the progression of deleterious
compensatory mechanisms of HF.
Several lines of evidence suggest greater aerobic and cardiovascular adaptations after
high-intensity exercise than with moderate levels in patients with coronary artery disease
or left ventricular dysfunction function and in healthy subjects. Aerobic interval training
(AIT) involving periods at 90% of VO2peak has been shown to rescue impaired cardiomyocyte
contractility, attenuate myocardial hypertrophy, and reduce myocardial expression of atrial
natriuretic peptide in animal model of post-infarction heart failure. However, underlying
mechanisms of AIT-improved regulations remain unclear.
The different effects of AIT and moderate continuous training (MCT) on hemorheology,
atherothrombosis or angiogenesis modulated by erythrocyte, monocyte or EPC in patients with
CHF have been not investigated yet. Accordingly, the investigators will conduct this
three-year study to clarify how the two exercise trainings affect cardiovascular
hemorheological characteristics and atherothrombosis/ angiogenesis-related variables in
patients with chronic heart failure. The investigators expect that these results obtained
from this study can aid in determining appropriate exercise intervention to improve aerobic
fitness as well as simultaneously improve hemodynamic control and minimize the risk of
thrombogenesis in patients with CHF.
Heart failure (HF) is a major and increasingly common cardiovascular syndrome, and is the
end result of many cardiovascular disorders. It has been reported that HF patients with
pharmacological therapy often remain burdened by dyspnea and fatigue, diminished exercise
tolerance, reduced quality of life, recurrent hospitalizations, and early mortality. HF is
associated with neurohumoral changes as the body attempts to reverse the effect of reduced
cardiac output and organ perfusion. Persistent neurohumoral excitation, however, actually
results in deterioration of myocardial function with inflammatory response, end-organ
damage, and skeletal muscle derangement, which lead to worsened exercise capacity.
Physical training can have beneficial effects on neurohumoral, inflammatory, metabolic and
central hemodynamic responses, as well as on endothelial, skeletal muscle and cardiovascular
function, leading to improvement in functional capacity and quality of life. All these
training-induced changes can effectively counteract the progression of deleterious
compensatory mechanisms of HF. Which exercise intensity yields maximal beneficial
adaptations is controversial.
Several lines of evidence suggest greater aerobic and cardiovascular adaptations after
high-intensity exercise than with low and moderate levels in patients with coronary artery
disease or left ventricular dysfunction function and in healthy subjects. Aerobic interval
training (AIT) involving periods at 90% of VO2peak has been shown to rescue impaired
cardiomyocyte contractility, attenuate myocardial hypertrophy, and reduce myocardial
expression of atrial natriuretic peptide in animal model of post-infarction heart failure.
However, underlying mechanisms of AIT-improved regulations of cardiac hemodynamics and risk
factors in patients with CHF remain unclear.
Pathological erythrocyte deformability and aggregation reduces capillary perfusion and
oxygen transfer to tissue, resulting in tissue ischemia or infraction. Shedding of
procoagulant-rich microparticles from activated monocytes can accelerate the pathogenesis of
atherothrombosis. Bone marrow-derived, circulating endothelial progenitor cells (EPC) is
contributes to the maintenance of endothelial function and organ perfusion by mechanisms
ranging from endothelial repair to angiogenesis. However, the different effects of AIT and
moderate continuous training (MCT) on hemorheology, atherothrombosis or angiogenesis
modulated by erythrocyte, monocyte or EPC in patients with CHF have been not investigated
yet.
Accordingly, we will conduct this three-year study that includes 1st year study: the effects
of AIT and MCT on hemorheology modulated by erythrocyte in patients with CHF; 2nd year: the
effects of AIT and MCT on atherothrombosis modulated by monocyte in patients with CHF; and
3rd year study: the effects of AIT and MCT on angiogenesis modulated by EPC in patients with
CHF to clarify how the two exercise trainings affect cardiovascular hemorheological
characteristics and atherothrombosis/ angiogenesis-related variables in patients with
chronic heart failure. We expect that these results obtained from this study can aid in
determining appropriate exercise intervention to improve aerobic fitness as well as
simultaneously improve hemodynamic control and minimize the risk of thrombogenesis in
patients with CHF.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment