Alleviation of myocardial ischemia after Kawasaki disease by heparin and exercise therapy

Background-Heparin promotes angiogenesis. We evaluated the effects of combi ned treatment with heparin and exercise on myocardial ischemia in the chron ic stage of Kawasaki disease. Methods and Results-This study was conducted in 7 patients (aged 6 to 19 ye ars) who had a totally occluded coronary artery and stress-induced myocardi al ischemia in the collateral-dependent areas. Twice-daily exercise using a bicycle ergometer was performed with increments of 0.5 W/kg every 3 minute s up to maximal exertion for 10 days. Heparin, which immediately increased circulating hepatocyte growth factor, was given intravenously 10 minutes be fore each exercise period. Newly developed myocardial infarction, ventricul ar tachyarrhythmia, anginal attack, or hemorrhagic complication was not obs erved in any patient. Dipyridamole-loading single photon emission computed tomography documented improved myocardial perfusion in the collateral-depen dent areas and a significant reduction in total defect scores in all patien ts after the completion of 20 sessions (P=0.01). In control patients who di d not receive the heparin-exercise therapy, however, stress defect scores r emained unchanged (n=1) or increased (n=2) during follow-up. Computerized q uantitative coronary angiography provided evidence that the heparin-exercis e therapy increased the diameter of the occluded artery to which collateral s terminated (P=0.001) but not that of the reference artery with which coll aterals were not connected (P=0.96). Conclusions-The findings suggest that a series of heparin and exercise trea tments over 10 days may have a dramatic effect on the alleviation of myocar dial ischemia in colateral-dependent regions. This may be a safe, noninvasi ve revascularization therapy for patients with coronary artery occlusion in the chronic stage of Kawasaki disease.