Exercise increased the growth of new muscle cells and blood vessels in the weakened muscles of people with heart failure, according to two new studies.
"If you have heart failure, exercise training can improve your health status, increase your ability to exercise and reverse patterns of muscle damage that are common in heart failure," said Axel Linke, M.D., assistant professor of medicine at the University of Leipzig, Germany, and a co-author on both studies.
In chronic heart failure, the heart can't pump enough blood to other organs in the body.
"In addition to getting out of condition because it becomes difficult to exercise, people with heart failure have cellular-level changes in their muscles that make them weaker, more prone to fatigue, and in later stages results in actual muscle shrinkage," he said.
In one study (abstract 3797), researchers investigated whether exercise training could activate progenitor cells, a pool of immature cells in skeletal muscle that can divide into various mature cells as needed for muscle repair.
Compared with healthy people, those with heart failure have about a 50 percent reduction in the number of progenitor cells in their muscles, Linke said.
Researchers examined biopsies of the vastus lateralis, the largest quadricep muscle in the outer thigh, in 50 men, average age 56, with moderate to severe heart failure -- a level at which any exercise is uncomfortable. Researchers took the biopsies before and after a six-month period in which 25 men remained inactive and the other 25 participated in an individualized, physician-supervised endurance exercise program.
Study participants rode a stationary bicycle at least 30 minutes a day (usually divided into two sessions) at about half their peak exercise capacity.
At the end of the six-month study, levels of progenitor cells stayed the same in the inactive group but changed significantly in the exercisers:
- Total number of progenitor cells (identified by c-kit+ protein marker on the cell surface) increased by 109 percent.
- Progenitor cells differentiating into muscle cells (identified by c-kit/MEF2+ marker) increased by 166 percent.
- Progenitor cells actively dividing to form new cells and repair muscle damage (identified by c-kit/Ki67+ protein marker) significantly increased six-fold.
"With exercise, the number of progenitor cells became almost normal, the cells started to divide again, and they began to differentiate into myocytes (muscle cells). And that's exactly what patients with heart failure need -- replacement of muscle cells," Linke said.
Participants in the exercise program also felt better and increased their exercise capacity 20 percent during the six-month study, Linke said.
Whether exercise can induce similar changes in heart muscle is not known, researchers said.
"We also have c-kit+ cells in the heart but we don't know whether they are similar to those in skeletal muscle," Linke said.
In the second study (abstract 3796), researchers tracked endothelial progenitor cells that are created in bone marrow and circulate through the bloodstream. The cells help repair damaged blood vessel linings and spur new vessels to form in a process called vasculogenesis.
In heart failure, the linings of blood vessels are damaged, blood vessels in muscle do not dilate normally, and the number of small blood vessels (capillaries) in muscle tissue is reduced.
Researchers randomly assigned 37 men, average age 65, with severe heart failure to receive either 12 weeks of exercise training or to remain inactive. They took blood tests and biopsies of the quadricep muscle before and after the program. After 12 weeks, researchers found no changes in men assigned to the control group. In contrast, exercisers changed significantly:
- Circulating progenitor cells (identified by CD34+ marker) increased 47 percent.
- Circulating progenitor cells beginning to mature into endothelial cells (identified by CD34/KDR+ marker) significantly increased 199 percent.
- Functional activity of the circulating progenitor cells (measured by migratory capacity) significantly increased 149 percent.
- The density of capillaries in skeletal tissue significantly increased 17 percent.
"Whether you have moderate or severe heart failure, you can benefit from exercise therapy," Linke said. "These studies show that the benefits come from both the regeneration of muscle cells and the formation of blood vessels."
More than 5 million people in the United States have heart failure. About 1 percent of people over age 65 start having heart failure annually.
Co-authors of both studies are Volker Adams, Ph.D., presenter; Sandra Erbs, M.D.; Robert Höllriegel, M.D.; Ephraim B. Beck, M.D.; Stephan Gielen, M.D.; Sven Möbius-Winkler, M.D.; Rainer Hambrecht, M.D.; and Gerhard Schuler, M.D.
These studies were reported at the American Heart Association's Scientific Sessions 2007. The German Heart Foundation funded the studies.
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