Effects of Adenosine Infusion During Reperfusion After Cold Cardioplegic Ischemia in Neonatal Lambs

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Abstract

Background.

Postischemic infusion of adenosine (Ado) has been postulated to reduce reperfusion injury after normothermic ischemia, but the effect of Ado after hypothermic ischemia is unknown.

Methods and Results.

######We infused Ado (350 μmol/L), Ado+Ado antagonist theophylline (Ado+T, 7 mmol/L), A#####1###### agonist cyclohexyl-Ado (0.25 μmol/L), A#####2###### agonist cyclopropyl carboxamide Ado (0.25 μmol/L), or blood alone (group C) during the first 20 minutes of reperfusion after 2 hours of cold cardioplegic ischemia using an isolated, blood-perfused neonatal lamb heart model (n=8 in each group). At 30 minutes of reperfusion, left ventricular (LV) maximum developed pressure (DP), dP/dt, -dP/dt, maximum DP at V10 (volume that gives LVEDP of 10 mm Hg at baseline measurement), dP/dt at V10, and LV stiffness constant (###K#########A######) at V10 were measured. Coronary blood flow and oxygen consumption (MV̇o#####2######) were also measured to evaluate the metabolic recovery. Groups Ado, A#####1######, and A#####2###### showed better functional recovery than group C (DP for group C, 74.6±5.60%; group Ado, 94.2±10.7%; group A#####1######, 89.3±4.40%; group A#####2######, 86.7±9.00%; ###P####<.01), but theophylline offset the Ado effect (Ado+T, 74.6±6.4%). Coronary blood flow was higher in groups Ado+T and A#####2###### than group C (group C, 156.7±45.7%; group Ado+T, 238.0±41.0%; group A#####2######, 258.6±70.3%; ###P####<.05). MVo#####2###### was higher in groups Ado, Ado+T, A#####1######, and A#####2###### than group C (group C, 57.7±11.0%; group Ado, 91.5±20.1%; group Ado+T, 210.7±60.0%; group A#####1######, 82.8±31.9%; group A#####2######, 83.5±12.8%; ###P####<.05).########

Conclusions.

Ado infusion improved recovery of mechanical function after hypothermic ischemia, and its beneficial effect appears to involve both A1 and A2 receptors. Since group Ado+T had high coronary blood flow but not improved systolic function and group A1 had low coronary blood flow and improved systolic function, coronary vasodilation alone is not responsible for this beneficial effect. Ado may be a useful agent after hypothermic ischemia in the immature heart, although the precise mechanisms remain unclear. (Circulation.1993;88[part 2]:380–386.)

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