Effects of OG-VI, a nucleosideucleotide mixture, on stunned myocardium in dogs: is the adenosine A1 receptor involved?

摘要

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 7.5 mmol/l thymidine; it limits myocardial stunning in dogs. We examined whether adenosine A1 receptors were involved in the mechanism of action of OG-VI. METHODS: Dogs anesthetized with pentobarbital were subjected to 20 min of left anterior descending coronary artery ligation followed by 30 min of reperfusion. Saline, OG-VI in several doses, adenosine or inosine was infused at 0.1 ml/kg/min, starting 30 min before the ischemia. In some experiments, 1 or 3 mg/kg 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, was injected intravenously 15 min before the start of the OG-VI infusion. The percentage myocardial segment shortening (%SS) was measured by sonomicrometry. The tissue concentration of ATP was measured in the 30-min-reperfused hearts. RESULTS: In the saline group, %SS that had been decreased by ischemia returned toward pre-ischemic values after reperfusion, although the metabolic recovery was incomplete, with a low concentration of ATP. The %SS was almost completely restored by 12 and 1.2 mumol/kg/min OG-VI, but 0.4 mumol/kg/min was less effective. Administration of adenosine or inosine did not modify the changes in %SS during ischemia/reperfusion. Pretreatment with DPCPX worsened the recovery of %SS during reperfusion after ischemia in both the saline and the OG-VI groups. Infusion of DPCPX (3 mg/kg) with saline caused the animals to die shortly after the onset of ischemia. However, the enhancement of %SS recovery during OG-VI reperfusion was observed in the presence of DPCPX. CONCLUSION: OG-VI improves the recovery of %SS during reperfusion after brief ischemia in a dose-dependent manner. This effect is not brought about by stimulation of adenosine A1 receptors.