Cardiac microdialysis measurement of extracellular adenine nucleotide breakdown products during regional ischemia and reperfusion in canine heart: protective effect of propranolol against reperfusion injury.
Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations reached maximum values not at the end of ischemia but in the first 10 min of reperfusion. The effect was more pronounced after 20-min ischemia. Further reperfusion led to an ANBP decrease that was more prolonged after 40-min ischemia. Pretreatment with DL-propranolol (0.5 mg/kg, intravenously, i.v.) given 40 min before coronary occlusion had no effect on adenine nucleotide catabolism rate during 20- and 40-min ischemia, but it facilitated washout of ANBP from ischemic zone immediately after the start of reperfusion. A similar effect was elicited by a D-stereoisomer of propranolol with no beta-adrenoceptor blocking activity. Results suggest that the reperfusion injury and probably the no-reflow phenomenon were the cause of enhanced adenine nucleotide catabolism at the beginning of reperfusion and prolonged ANBP washout from the ischemic zone. Reduction of reperfusion injury by propranolol could be related to the membrane stabilizing and antioxidant activity of this agent. Examination of DL-propranolol kinetics in arterial and coronary venous blood plasma showed that drug accumulation in the myocardium was almost maximum at the start of ischemia; therefore, the efficiency of cardio-protection with DL-propranolol was not limited by pharmacokinetic causes. Insertion of an additional microdialysis probe in the myocardium allowed monitoring of extracellular propranolol concentrations.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D007042:Hypoxanthines / Q000378:metabolism; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011433:Propranolol / Q000627:therapeutic use*; D013056:Spectrophotometry, Ultraviolet
D000227:Adenine Nucleotides; D007042:Hypoxanthines; D007288:Inosine; D011433:Propranolol