Elevation of plasma adenosine levels may attenuate the severity of chronic heart failure

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.