After the doxorubicin regimen (total dose of 15 mg/kg intraperitoneally, divided at six time points, every third day for 14 days to induce congestive heart failure), and after four weeks of rest, assessed in mice and rats with advanced disease, the increased big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT), before and after the subsequent 14 days of therapy, and clinical status (hypotension, increased heart rate, and respiratory rate, and ascites) every two days [84]. Here, EDN1 is linked to congestive heart failure.