Effects Of Adenosine On Energy Substrate Metabolism During Ischemia And Reperfusion In Isolated Working Rat Hearts(Mechanism Studies Of Cardioprotection Of Adenosine)

Adenosine, an endogenous nucleoside, is an important metabolite intermediate and exerts widespread regulatoiy and control throughout the body by interacting with specific cell-surface adenosine receptors. It is said that adenosine possesses marked cardioprotective properties, but the mechanisms for this beneficial effect are unclear. The role of adenosine in cardiac energy metabolism as a homeostatic metabolite has recently attracted much attention. The cardiovascular effects of adenosine appear to regulate the balance between 02 supply and energy demand, and the formation of adenosine is facilitated during periods of energy deficit. This provides a sensitive link between cardiac metabolic activity and adenosine release. The objective of this study was to determine the effect of adenosine on mechanical function, exogenous glucose oxidation, glycolysis, metabolite levels, and ultrastructure changes of heart cells in isolated working rat hearts perfused with glucose and fatty acids. Meanwhile, glycolysis, oxidation, H+ production, metabolite levels, and ultrastructure changes in hearts subjected to antecedent ischemic stress (AIS) (not ischemic preconditioning) and subsequent ischemia and reperfusion was studied. The effect of phentolamine-an a -adrenoceptor antagonist in preventing adenosine-induced stimulation of glycolysis and reduced H+ production from glucose was also studied. The main work was described as foliows: 1. Establishment the model of isolated working rat hearts The model, reported by Neely et al, was established in Hearts from male Sprague-Dawley rats perfused with non-recirculating Krebs-Henseleit solusion (37℃, pH 7.4, gassed with a 95%O2-5%CO2 mixture). It is a biperfusing system because the Langendorff perfusion was attached. The model well mimicked the hearts in vivo. Perfusions were performed at a constant 1.5kPa left atrial preload and 1O.7kPa aortic 5 aflerload. The non-recirculating perfusion avoided the cumulation of metabolites and kept the the same baseline during the perfusion. It provide lots of help for the subsequent research work. 2. Adenosine altered glucose metabolism and mechanical function during ischemia and reperfusion in isolated rat heart In isolated working rat hearts perfused with modified Krebs-Henseleit solution containing 2. 5mM free Ca2~, 11mM glucose, 1.2mM palmitate pre-bound to 3% bovine serum albumin, 500 ju U/mi insulin, adenosine (100 ~.t M) pretreatment or adenosine (100 ~ M) at reperfusion markedly increased the recovery of mechanical function (from 12.31 ?7.68% to 70.58 ?24.84% and 69.05 ?12.88%, respectively) after 60 minutes of low-flow ischemia (coronary flow