May 31, 2001 DALLAS, May 29 – A new therapy using the anti-clotting drug heparin and 10-minute spurts of exercise grew new blood vessels and widened blocked arteries in children with Kawasaki disease, according to a report in today’s Circulation: Journal of the American Heart Association.
Kawasaki disease (KD) is characterized by fever, rash, swollen hands, feet and lymph nodes, and inflammation of the mouth, lips and throat. Its cause is unknown. About 80 percent of cases occur in children younger than age 5, and in as many as 20 percent of children with KD, the heart is affected.
The coronary arteries or the heart muscle can be damaged and susceptible to atherosclerosis. “Some Kawasaki patients are unable to have surgical or catheter revascularization procedures because of the extent of their disease,” says Masaru Terai, M.D., co-author of the study and head of the cardiology division at Chiba University School of Medicine in Japan. “Our study may provide another therapeutic option for these cases.”
Researchers studied seven children, ages 6 to 19 years old, who had a totally blocked coronary artery and were ineligible for angioplasty or surgical revascularization. The children exercised on a stationary bicycle twice a day for 10 days, gradually increasing intensity. Each session lasted about 10 minutes. Heparin was given 10 minutes before each exercise session. Heparin promotes angiogenesis, which is the development of new blood vessels.
Terai’s team examined the blood flow around the children’s artery blockages using angiography, an X-ray of the blood vessels. Angiography was performed one to three months before the heparin/exercise treatment and again within three months following the completion of 20 treatment sessions in six of the children. The follow-up angiography was not performed on the seventh patient.
The average time between the initial and final angiography was about five months. The final angiography showed that a network of tiny new blood vessels had formed in two of the patients. In all participants, angiography showed that heparin/exercise therapy increased the size of the blocked artery, thus allowing more blood to pass through. The diameter of the blocked artery widened from 1.21 millimeters (mm) to 1.35 mm.
Researchers also used single photon emission computed tomography (SPECT) to evaluate the flow and volume of blood to the heart muscle around the occluded artery. SPECT produces X-ray-like images that, in this study, were graded on a 3-point scale in 17 regions of the heart with a 0 indicating normal blood flow. A patient’s total score was derived from adding the scores in all 17 regions.
At the beginning of the study, and again within a week after the last heparin/exercise session, patients underwent SPECT imaging at rest and after taking a drug called dipyridamole, which mimics the effects of physical stress on the heart. The SPECT images of the study patients were compared to those of three children with KD who did not undergo heparin/exercise therapy.
In all seven children, the heparin/exercise therapy was associated with improved blood flow to the heart muscle in the areas around the blockage. Their average SPECT scores after dipyridamole decreased from 14.2 to 8.3. In the control group, the incidence of stress-induced heart damage remained unchanged or increased, and average SPECT scores after dipyridamole increased from 8.1 to 11.4. None of the children showed evidence of new heart damage. “Previous studies of patients with angina have shown that exercise capacity was not improved by heparin or exercise alone,” says Terai. “This implies that the combination of heparin and physical stress is required for improvement in collateral circulation.”
Terai says other studies have shown that ischemia, meaning loss of blood flow that can result in tissue damage, increases the body’s production of angiogenic growth factors. “Although we did not have direct evidence of new blood vessels in the ischemic regions of the heart, there was evidence for increased blood flow to the areas, as shown by improved SPECT scores. “The heparin and exercise treatment protocol seems remarkably safe, inexpensive, and easy to perform. KD patients who have developed some collateral circulation for a blocked artery are good candidates for this therapy,” he says.
“Kawasaki disease and acute rheumatic fever are the two leading causes of acquired heart disease in children in the United States,” says Kathryn A. Taubert, Ph.D., vice president of science and medicine for the American Heart Association. “The findings from this study provide an encouraging step forward in treating children with this disease.”
Terai and his colleague’s are now investigating mid-term outcomes of heparin and exercise therapy and will report those findings soon.
Other researchers include Shigeru Tateno, M.D., Koichiro Niwa, M.D.; Toshiaki Jibiki, M.D.; Hiromichi Hamada, M.D.; Kumi Yasukawa, M.D.; Takafumi Honda, M.D.; Shinji Oana, M.D.; and Yoichi Kohno, M.D.
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