Ischemic preconditioning in immature myocardium

BACKGROUND: Protection by ischemic preconditioning (PC) has not been studied extensively in immature hearts. We studied the developmental differences in the ability of the rat heart to precondition with ischemia.

METHODS AND RESULTS: Hearts from 4-, 7-, 14-, and 21-day-old and adult (approximately 50-day-old) rats were aerobically perfused in Langendorff mode before a PC stimulus of either (1) 3-minute ischemia (I), 3-minute reperfusion (R), 5-minute I, 5-minute R, or (2) 4 cycles of 5-minute I and 5-minute R, before a prolonged I (chosen to give 30% to 40% recovery) and 60-minute R. LVDP recovery was expressed as percent of baseline reading (after 20-minute aerobic perfusion). Protection was seen after protocol 1 in 14- and 21-day-old and adult hearts (45 +/- 5%, 53 +/- 7%, and 58 +/- 5% versus 30 +/- 4%, 29 +/- 3%, and 32 +/- 2% in controls, respectively) but not in 4- and 7-day (neonatal) hearts; neonatal hearts were also not protected in protocol 2. To determine whether this inability of neonatal hearts to precondition was due to insufficient duration of the PC cycle, they were subjected to increased I durations up to 20 minutes before 5-minute R, prolonged I (90 minutes and 60-minute R) (protocol 3); protection was not seen. To determine whether the inability to precondition was due to an excessively prolonged ischemic duration, neonatal hearts were subjected to only 45 minutes of prolonged I (protocol 4); again, PC protection was not evident.

CONCLUSIONS: Protection by PC develops after 7 days; the inability of neonatal hearts (< 7 days old) to precondition is not due to insufficient stimulus or extended ischemia.