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(Circulation. 1999;99:1249-1254.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Preconditioning in Immature Rabbit Hearts

Role of K_ATP Channels

John E. Baker, PhD; Patricia Holman, BS; Garrett J. Gross, PhD

From the Division of Cardiothoracic Surgery (J.E.B., P.H.) and Department of Pharmacology and Toxicology (J.E.B., G.J.G.), Medical College of Wisconsin, Milwaukee, Wis.

Background—The protective effects of ischemic preconditioning have been shown to occur in adult hearts of all species studied. We determined whether immature hearts normoxic or chronically hypoxic from birth could be preconditioned, the time window or memory of the cardioprotective effect, and the involvement of the K_ATP channel.

Methods and Results—Isolated immature rabbit hearts (7 to 10 days old) were subjected to 0, 1, or 3 cycles of preconditioning consisting of 5 minutes of global ischemia plus 10 minutes of reperfusion. This was followed by 30 minutes of global ischemia and 35 minutes of reperfusion. Normoxic hearts (FIO₂=0.21) subjected to 1 cycle of preconditioning recovered 70±7% of left ventricular developed pressure compared with 43±8% recovery in nonpreconditioned controls. Three cycles of preconditioning did not result in additional recovery (63±8%). Hearts from rabbits raised from birth in hypoxic conditions (FIO₂=0.12) and subjected to 1 and 3 preconditioning cycles did not show increased recovery (68±8% and 65±5%) compared with nonpreconditioned hypoxic controls (63±9%), although the recovery was greater in chronically hypoxic hearts than in age-matched normoxic controls. Increasing the recovery period after the preconditioning stimulus from 10 to 30 minutes resulted in a loss of cardioprotection. Pretreatment of normoxic hearts for 30 minutes with the K_ATP channel blocker 5-hydroxydecanoate (300 µmol/L) completely abolished preconditioning (70±7% to 35±9%) but had no effect on nonpreconditioned hearts (40±8%).

Conclusions—Immature hearts normoxic from birth can be preconditioned, whereas immature hearts hypoxic from birth cannot. Preconditioning in normoxic immature hearts is associated with activation of the K_ATP channel.

Key Words: cardiovascular diseases • heart defects, congenital • hypoxia • ions • ischemia

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