[A study on the interstitial level of endogenous adenosine and its cardioprotective effect during ischemia/reperfusion in the canine heart].
The role of endogenous adenosine on the functional recovery of the heart reversibly injured by ischemia/reperfusion (stunned myocardium) was studied in in vivo canine hearts. Anesthetized open-chest dogs (n = 37) were subjected to 15-min left anterior descending artery (LAD) occlusion followed by 60-min reperfusion. Group 1 (n = 13) received saline and group 3 (n = 9) received an adenosine potentiator, dipyridamole (20 micrograms/kg/min, i.v.), from 15 min before LAD occlusion for 45 min. Group 2 (n = 8) and group 4 (n = 7) were pretreated with an adenosine blocker, 8-phenyltheophilline (8-PT; 10 mg/kg, i.v.), before the saline or dipyridamole infusion, respectively. Interstitial levels of adenosine and its metabolites were measured using cardiac microdialysis technique. Regional cardiac function in the ischemic area was assessed by segment shortening (%SS) with ultrasonic crystals. The dialysate concentration of adenosine in the ischemic region increased from 0.32 to 1.90 microM by the 15-min LAD occlusion in group 1. Dipyridamole enhanced this increase in adenosine to 5.51 microM, with a significant improvement of %SS (36.8 vs. 61.0% at 60 min after reperfusion in group 1 and group 3, respectively; each preischemic level: 100%). Pretreatment with 8-PT did not modify the change of adenosine level in groups 2 and 4, however, significantly deteriorated %SS compared with groups 1 and 3, respectively. Hemodynamic parameters were not statistically different among 4 groups throughout the experiment. Thus, endogenous adenosine was clearly demonstrated to protect stunned myocardium against ischemia/reperfusion. The enhancement of cardiac interstitial level of adenosine with adenosine potentiators, such as dipyridamole, may be expected to ameliorate cardiac function during coronary recanalization therapy or cardiac surgery.
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
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Numazawa
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D004176:Dipyridamole / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D008297:Male; D017551:Microdialysis; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D004176:Dipyridamole; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine