RELATIONSHIP OF BLOOD-FLOW EFFECTS OF ADENOSINE DURING REPERFUSION TORECOVERY OF VENTRICULAR-FUNCTION AFTER HYPOTHERMIC ISCHEMIA IN NEONATAL LAMBS

Background Previous experiments have shown that infusion of either ade nosine (ADO) or an adenosine receptor agonist during reperfusion after hypothermic ischemia improved the recovery of ventricular function in neonatal lamb hearts. Adenosine has multiple actions that might be be neficial during postischemic reperfusion, and the A(2) effects include both coronary vasodilator and leukocyte inhibitory effects. In the cu rrent experiment we investigated the relationship between the coronary blood flow (CBF) effects of A(2) stimulation and the recovery of post ischemic ventricular function. Methods and Results Two hours of 10 deg rees C cardioplegic ischemia was induced in 40 isolated, blood-perfuse d, neonatal lamb hearts (n=8 in each group). Group I had ischemia foll owed by unmodified reperfusion for 90 minutes. During the first 20 min utes of reperfusion, Group IT received 350 mu mol/L ADO, Group III rec eived ADO and 100 nmol/L DPCPX (A(2) antagonist) to achieve an A(2) ef fect, Group TV received 0.25 mu mol/L CPCA (A(2) agonist), and Group V received ADO and DPCPX but CBF was limited to that of Group I levels. At 30 and 90 minutes of reperfusion, LV maximum developed pressure (D P), dP/dt, CBF, and oxygen consumption (MVo(2)) were measured. At 30 m inutes of reperfusion Groups II, III, and IV showed better functional recovery than Group I or Group V (DP: G-I=75.7+/-7.3%, G-II=97.6+/-9.5 %, G-III=88.1+/-4.8%, G-IV=86.7+/-9.0%, G-V=75.5+/-6.9%, P<.05; dP/dt: G-I=69.1+/-9.6%, G-II=94.2+/-10.7%, G-III=95.7+/-13.1%, G-IV=80.1+/-1 1.1%, G-V=75.2+/-8.2%, P<.05). Coronary blood flow was higher in Group s II, III, and IV compared with Group I or V (G-1=129+/-32%, G-II=183/-36%, G-III=266+/-72%, G-IV=259+/-70%, G-V=132+/-5%, P<.05). MVo(2)/b eat was higher in Group II than in Groups I and TV (G-I=98.3+/-21.3%, GII=135.5+/-28.0%, G-III=126.2+/-21.9%, G-IV= 102.5+/-16.7%, G-V=107.5 +/-29.3%, P<.05). At 90 minutes of reperfusion, Groups II, III, and IV , as well as V, showed better recovery of DP and dP/dt compared with G roup I (DP: G-I=50.6+/-11.4%, G-II=63.0+/-8.7%, G-III=69.0+/-10.8%, G- IV=72.5+/-12.7%, G-V=66.2+/-10.0%, P<.05; dP/dt: G-I=38.9+/-7.1%, G-II =53.5+/-3.8%, G-III=61.5+/-10.8%, G-IV=59.8+/-16.3%, G-V=58.2+/-9.8%, P<.05) although only in Groups III and IV was CBF higher than in Group I (G-1=116+/-54%, G-II=116+/-27%, G-III=210+/-67%, G-IV=239+/-85%, G- V=130+/-8%, P<.05). Conclusions Reperfusion under conditions of A(2) s timulation by ADO, by an A(2) agonist, or by ADO plus A(2) blockade wa s associated with improved recovery of LV function. The early A(2) eff ect seems to be related to coronary vasodilation because reduced CBF ( equal to Group I) in Group V reduced early recovery of LV function. Ho wever, there seems to be a second effect observed at 90 minutes that i s not related to CBF inasmuch as Groups II and V had CBF equal to Grou p I but had significantly higher DP and dP/dt. These findings suggest that mechanisms in addition to vasodilation are involved in the benefi cial effects of A(2) stimulation during postischemic reperfusion.