Adenosine is known to be an endogenous cardioprotective substance. Since we have reported that
adenosine levels increase in patients with chronic
heart failure, we tested whether further elevation of the
adenosine levels due to
dipyridamole or
dilazep for 6 months modulates the pathophysiology of chronic
heart failure. In patients with chronic
heart failure, either
dipyridamole (300 mg/d n = 17) or
dilazep (300 mg/d n = 5) were administered for 6 months. Twenty-two patients (mean +/- SE age 58 +/- 4 years old) attending a specialized chronic
heart failure (CHF) clinic over 6 months and judged as in New York Heart Association (NYHA) function class II or III were examined. The other drugs used for the treatment of CHF were not altered during the study. There were 5 patients with CHF caused by
ischemic heart diseases, and 17 patients with either
valvular heart diseases or
dilated cardiomyopathy. We found that increases in the plasma
adenosine levels (202 +/- 34 and 372 +/- 74) nmol/L before and after
dipyridamole administration, P < 0.005 ameliorate the severity of CHF (NYHA: 2.1 +/- 0.5 to 1.7 +/- 0.2). Both ejection fraction and maximal oxygen consumption increased. These improvements in the severity of chronic
heart failure returned to baseline levels 6 months after discontinuation of
dipyridamole. Comparable results were obtained in the
dilazep protocol. We suggest that the elevation of plasma
adenosine levels improves the pathophysiology of CHF.