Limitation of stunning in dog myocardium by nucleoside and nucleotide mixture, OG-VI.
OG-VI is a solution composed of 30 mM inosine, 30 mM sodium 5'-guanylate, 30 mM cytidine, 22.5 mM uridine, and 7.5 mM thymidine, expecting to use for total parenteral nutrition. We examined the effect of OG-VI on myocardial contractile dysfunction during reperfusion after ischemia (myocardial stunning) in dogs. Pentobarbital-anesthetized dogs were subjected to 20-min left anterior descending coronary artery ligation followed by 30-min reperfusion. Saline, OG-VI or its constituents [inosine and sodium 5'-guanylate mixture (IG), and cytidine, uridine, and thymidine mixture (CUT)], or 5-amino-4-imidazole carboxamide riboside (AICAr) was infused at 0.1 mL.kg-1.min-1, starting 30 min before the ischemia. The contractile function was determined by ultrasonometry and assessed as % segment shortening (%SS). %SS was markedly decreased by ischemia, and returned toward pre-ischemic level after reperfusion, although the recovery was incomplete. The %SS was almost completely recovered by OG-VI and IG, and to a lesser extent by AICAr; CUT was ineffective. In the presence of 1 mg.kg-1 of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, a selective adenosine A1 receptor antagonist), cardioprotective effect of OG-VI on stunned myocardium was still observed. In conclusion, infusion of OG-VI improved myocardial contractile dysfunction in stunned myocardium. This effect was more potent than its constituents and AICAr. Adenosine A1 receptors are not involved in the mechanism.
Ichihara
K
K
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Kano
S
S
Satoh
K
K
Nakai
T
T
Fukutomi
T
T
Okazaki
Y
Y
Kohri
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D006157:Guanosine Monophosphate / Q000494:pharmacology; D007288:Inosine / Q000494:pharmacology; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects; D017682:Myocardial Stunning / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D009705:Nucleosides / Q000494:pharmacology*; D009711:Nucleotides / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology
D002316:Cardiotonic Agents; D009705:Nucleosides; D009711:Nucleotides; C087081:OG-VI solution; D018047:Receptors, Purinergic P1; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D007288:Inosine; D006157:Guanosine Monophosphate; D000255:Adenosine Triphosphate; C031143:AICA ribonucleotide