Beneficial metabolic effect of nucleoside augmentation on reperfusion injury following cardioplegic arrest.
Restoration of coronary flow after hyperkalemic cardioplegic arrest (HCA) is associated with a unique metabolic reperfusion injury (RI) manifested by declining nucleotide stores despite their end-ischemic preservation. Prevention of this RI by exogenous provision of adenosine with or without inhibition of adenosine's major catabolic enzyme was assessed in 27 dogs subjected to 60 minutes of HCA. The effect of aortic root infusion of 40 mg/kg of adenosine in addition to adenosine deaminase inhibition by 10 mg/kg of EHNA (group 2) initiated during 60 minutes of reperfusion on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores and coronary blood flow (CBF) were compared to animals having adenosine infusion alone (group 3) or controls (group 1). Although ATP levels were preserved at the end of HCA in all groups, adenosine infusion with or without EHNA prevented the significant 23 percent decline in ATP stores incurred during unmodified reperfusion (p less than 0.01, group 1). The CP stores decreased (p less than 0.05, all groups) during arrest, but were restored to preischemic levels during reperfusion. When measured 60 minutes after aortic unclamping, CBF was 312 percent of preischemic flow in group 3 (p less than 0.01), only 170 percent in group 2 (p less than 0.05), and unchanged in controls (group 1). The data indicate that provision of adenosine as a nucleotide precursor prevents the metabolic RI following HCA. In addition, inhibition of adenosine catabolism is not necessary for this salutary effect, nor is adenosine's efficacy solely mediated by augmentation of CBF.
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000241:Adenosine / Q000627:therapeutic use*; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D006324:Heart Arrest, Induced; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D010725:Phosphocreatine; C010192:9-(2-hydroxy-3-nonyl)adenine; D000255:Adenosine Triphosphate; D000225:Adenine; D000241:Adenosine