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 (350μmol/L), Ado+Ado antagonist theophylline (Ado+T, 7 mmol/L), A1 agonist cyclohexyl-Ado (0.25, mol/L), A2 agonist cyclopropyl carboxamide Ado (0.25 pgmol/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 (KA) at V10 were measured. Coronary blood flow and oxygen consumption (MVo2) were also measured to evaluate the metabolic recovery. Groups Ado, A1, and A2 showed better functional recovery than group C (DP for group C, 74.6+5.60%o; group Ado, 94.2±10.7%; group A1, 89.3±4.40%o; group A2, 86.7±9.00%o; P<.01), but theophylline offset the Ado effect (Ado+T, 74.6±6.4%). Coronary blood flow was higher in groups Ado+T and A2 than group C (group C, 156.7±45.7%; group Ado+T, 238.0±41.0%; group A2, 258.6±70.3%; P<.05). MVo2 was higher in groups Ado, Ado+T, A1, and A2 than group C (group C, 57.7±11.0%'Y; group Ado, 91.5±20.1%; group Ado+T, 210.7±60.0%:; group A1, 82.8+31.9%o; group A2, 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 A, 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.

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