Relationship of blood flow effects of adenosine during reperfusion to recovery of ventricular function after hypothermic ischemia in neonatal lambs.

BACKGROUND

Previous experiments have shown that infusion of either adenosine (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 beneficial during postischemic reperfusion, and the A2 effects include both coronary vasodilator and leukocyte inhibitory effects. In the current experiment we investigated the relationship between the coronary blood flow (CBF) effects of A2 stimulation and the recovery of postischemic ventricular function.

METHODS AND RESULTS

Two hours of 10 degrees C cardioplegic ischemia was induced in 40 isolated, blood-perfused, neonatal lamb hearts (n=8 in each group). Group I had ischemia followed by unmodified reperfusion for 90 minutes. During the first 20 minutes of reperfusion, Group II received 350 micromol/L ADO, Group III received ADO and 100 nmol/L DPCPX (A1 antagonist) to achieve an A2 effect, Group IV received 0.25 micromol/L CPCA (A2 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 (DP), dP/dt, CBF, and oxygen consumption (MVO2) were measured. At 30 minutes 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+/-11.1%, G-V=75.2+/-8.2%, P<.05). Coronary blood flow was higher in Groups 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). MVO2/beat was higher in Group II than in Groups I and IV (G-I=98.3+/-21.3%, G-II=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 Group 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 A2 stimulation by ADO, by an A2 agonist, or by ADO plus A1 blockade was associated with improved recovery of LV function. The early A2 effect seems to be related to coronary vasodilation because reduced CBF (equal to Group I) in Group V reduced early recovery of LV function. However, there seems to be a second effect observed at 90 minutes that is not related to CBF inasmuch as Groups II and V had CBF equal to Group I but had significantly higher DP and dP/dt. These findings suggest that mechanisms in addition to vasodilation are involved in the beneficial effects of A2 stimulation during postischemic reperfusion.