title: Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit.
abstract: BACKGROUND
  We hypothesized that: (1) endogenous adenosine released during ischemia/reperfusion reduces infarct size and preserves postischemic myocardial blood flow by receptor-mediated mechanisms and (2) this cardioprotection is exerted predominantly during reperfusion.
  
  
  RESULTS
  Sixty-one anesthetized open-chest rabbits subjected to 30 minutes of coronary occlusion and 120 minutes of reperfusion were randomized to six groups: group 1, saline (Vehicle) (n = 10) to allow receptor interaction of endogenous adenosine (Ado) during ischemia/reperfusion; group 2, Ado-receptor blockade during both ischemia and reperfusion with intravenous 8-p-sulfophenyltheophyl-line (10 mg/kg) (SPTIR, n = 10); group 3, Ado-receptor blockade in multiple doses during both ischemia and reperfusion (MSPTIR, n = 11); group 4, blockade during reperfusion (SPTR, n = 10); group 5, blockade during reperfusion with PD115,199 (6 mg/kg) (PDR, n = 10); and group 6, blockade after 30 minutes of reperfusion (SPT30R, n = 10) to allow adenosine receptor interaction during early reperfusion. Transmural myocardial blood flow in the area at risk (Ar) (15-microns radiolabeled microspheres) was reduced by 96.7% in all groups, from 137.9 +/- 15.5 to 4.5 +/- 1.4 mL.min-1 x 100 g-1 (P < .001). MSPTIR, SPTIR, and SPTR significantly attenuated reactive hyperemia at 15 minutes of reperfusion (144 +/- 18, 141 +/- 22, and 144 +/- 20 mL.min-1 x 100 g-1, respectively) compared with Vehicle (257 +/- 40 mL.min-1 x 100 g-1, P < .05). This attenuation was more pronounced in the necrotic zone than in the nonnecrotic zone. Reactive hyperemia at 15 minutes of reperfusion in SPT30R group was comparable to the Vehicle group. At 120 minutes of reperfusion, blood flow in Ar was significantly less in MSPTIR (77 +/- 10), SPTIR (82 +/- 9), and SPTR (80 +/- 11) compared with Vehicle (140 +/- 12) and SPT30R (105 +/- 24 mL.min-1 x 100 g-1). Infarct size (by triphenyltetrazolium chloride), expressed as a percent of Ar, was largest in the multiple-dose group with blockade during both ischemia and reperfusion (MSPTIR, 51.9 +/- 2.3%) and was significantly increased also in single-dose SPTIR (39.1 +/- 2.2%) compared with 25.7 +/- 1.7% in the Vehicle group (P < .05). Ado-receptor blockade only during reperfusion was associated with 14% smaller infarct size in the SPTR group than the MSPTIR group (P < .05). In contrast, Ado-receptor blockade after 30 minutes of reperfusion (SPT30R) did not increase infarct size (27.9 +/- 2.2%), which was comparable to infarct size in the Vehicle group.
  
  
  CONCLUSIONS
  We conclude that: (1) endogenous adenosine released from the myocardium during ischemia/reperfusion reduces infarct size by receptor-mediated mechanisms and (2) Ado-mediated cardioprotection is most pronounced during the early phase of reperfusion.
authors.affiliation: Department of Cardiothoracic Surgery, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1096.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: S
authors.initials: S
authors.lastname: McGee
authors.forename: K
authors.initials: K
authors.lastname: Nakanishi
authors.forename: C F
authors.initials: CF
authors.lastname: Toombs
authors.forename: W E
authors.initials: WE
authors.lastname: Johnston
authors.forename: M S
authors.initials: MS
authors.lastname: Ashar
authors.forename: J
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D011983:Receptors, Purinergic / Q000502:physiology*
chemical_list: D011983:Receptors, Purinergic; D000241:Adenosine