Effects of OG-VI, a nucleoside/nucleotide mixture, and its constituents on myocardial stunning in dogs

Background: OG-VI is a solution composed of 30 mmol/l inosine, 30 mmol/l sodium 5'-guanylate, 30 mmol/l cytidine, 22.5 mmol/l uridine and 7.4 mmol/l thymidine, and has a protective effect on stunned myocardium. We examined the effects of the constituents of OG-VI on stunned myocardium in dogs, and compared them with that of acadesine (5-amino-4-imidazole carboxamide riboside; AlCAr) to try to elucidate the mechanism of the effect of OG-VI. Methods: Dogs anesthetized with pentobarbital were subjected to left anterior descending coronary artery ligation for 20 min followed by reperfusion for 30 min. Saline, OG-VI, its purine component (inosine and sodium 5'-guanylate; IG), its pyrimidine component (cytidine, uridine and thymidine; CUT) or AlCAr (30 mmol/l) was infused at 0.1 ml/kg/min, starting 30 min before the ischemia. Myocardial segment shortening function was determined by sonomicrometry. The tissue level of adenosine triphosphate (ATP) was determined in the hearts reperfused for 30 min. Results: Following reperfusion, the group treated with saline showed an incomplete recovery of segment shortening function, which had been decreased by ischemia, to the pre-ischemic level. The segment shortening function was almost completely recovered in the groups treated with OG-VI and IG, to a lesser extent in the AlCAr-treated group, and CUT was found to be ineffective. The levels of ATP in the OG-VI- and AlCAr-treated groups were significantly higher than that in the saline-treated group. In contrast to saline, IG and CUT were both ineffective at increasing ATP during reperfusion. Conclusion: Of the compounds tested, only OG-VI improves both ATP levels and segment shortening recovery in stunned dog myocardium. The increase in ATP levels is not the only factor responsible for contractile recovery.