Catabolism of adenine nucleotides in the human heart before and after cardiac bypass surgery

Uric acid (UA) is a catabolite of the high-energy purine phosphates and of purines in DNA and RNA. Thus, cardiac net release of UA could prevail in su bjects with chronic myocardial ischemia and during coronary occlusion assoc iated with cardiac artery bypass grafting surgery (CABG). However, in acute reperfusion, reactive oxygen species could cause chemical degradation of u rate, perhaps even giving rise to a negative coronary arteriovenous differe nce. Blood was sampled simultaneously from the arterial and coronary venous system of 24 patients undergoing elective CABG. Blood was immediately depr oteinated (0.4 M HClO4) in the presence of the glutathione-scavenger N-ethy lmaleimide (60 mM), and the supernatant was analysed for UA, purines, and g lutathione by high performance liquid chromatography. Before the operation, CABG patients revealed a small, but significant net production of UA in th e heart (+28 mu mol/liter whole blood; arterial level, 223 +/- 71 mu M; mea n +/- SD). There were no coronary differences for adenosine, inosine, or hy poxanthine. UA release was not elevated in early reperfusion after cardiac arrest and tended to decrease by 20-40 min of reperfusion (coronary sinus U A 10-18 mu M above arterial level, not significant). Adenosine levels were <0.2 mu M at all times in all blood samples. Coronary sinus (CS) inosine le vels rose approximately 10-fold during early reperfusion to 2 mu M (not sig nificant). However, CS hypoxanthine increased significantly from 8 (+/-3) t o 35 (+/-14) mu M at 1 min reperfusion, but after 5 min had returned to 15 mu M. There was a net release of reduced glutathione from the hearts before intervention, and individual changes in coronary glutathione levels were a pproximately parallel to those of urate in early reperfusion. Surprisingly, urate release did not correlate to the duration of cardiac ischemia (cross clamp time). Thus, in human hearts with chronic ischemia, myocardial releas e of uric acid is approximately 10-30% higher than the arterial input, indi cative of a pronounced catabolic state of the tissue. Metabolic recovery af ter CABG requires more than 1 h. Hypoxanthine (and not urate) is the better marker of acute myocardial nucleotide catabolism in early postischemic rep erfusion. Adenosine underlies a tight homeostasis in the coronary system. T he correlation of urate and glutathione release suggests that membrane pert urbation may accompany and/or contribute to nucleotide catabolism. Drug Dev . Res. 45:159-165, 1998. (C) 1998 Wiley-Liss, Inc.