Effects of dipyridamole on coronary collateralization and myocardial perfusion in patients with ischaemic cardiomyopathy

AIMS: There is evidence that oral dipyridamole, a nucleoside uptake blocker that increases myocardial adenosine levels, lessens myocardial ischaemia by inducing coronary collateral growth in animal models of ischaemic heart disease. However, whether dipyridamole can exert a similar effect in humans with coronary artery disease is controversial. METHODS AND RESULTS: We studied 30 male patients (mean age 55+/-9 years) with coronary artery disease and left ventricular systolic dysfunction (ejection fraction >40%). Patients were randomized into three matched groups. Group A patients (n=10) received dipyridamole alone at a dose of 75 mg t.i.d. orally for 8 weeks. Group B patients (n=10) underwent exercise training at 60% of peak .VO(2)three times a week for 8 weeks, and received dipyridamole. Group C patients (n=10) had neither exercise testing nor dipyridamole. On study entry and after 8 weeks all patients underwent an exercise test with gas exchange analysis, dobutamine stress echocardiography, 201-thallium planar myocardial scintigraphy, and coronary angiography. Peak .VO(2)increased significantly only in trained patients. Thallium uptake of the collateral-dependent myocardium, coronary collateral score and wall thickening score increased significantly only in groups receiving dipyridamole, the greatest improvement being in group B patients. Plasma adenosine levels were also the highest in group B (P<0.001 vs A and C). Correlations were found between changes in adenosine levels and increases of both thallium uptake (r=-0.70;P=0.001) and collateralization (r=0.72;P=0.001). CONCLUSION: Exercise training potentiates the effects of dipyridamole on coronary collateralization and myocardial perfusion in humans with ischaemic cardiomyopathy.