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Ischemic preconditioning in immature myocardium
W I Awad1, M J Shattock, D J Chambers
1Rayne Institute, St Thomas' Hospital, London, UK.
Insights
Ischemic preconditioning (PC) protects adult rat hearts but not neonatal hearts. Protection develops after 7 days of age, with immature hearts (<7 days) unable to precondition effectively.
Area of Science:
- Cardiovascular Physiology
- Neonatal Cardiology
- Ischemic Preconditioning
Background:
- Ischemic preconditioning (PC) offers cardioprotection but has been understudied in immature hearts.
- Investigating developmental differences in the rat heart's response to PC is crucial.
Purpose of the Study:
- To examine the developmental trajectory of ischemic preconditioning (PC) in the immature rat heart.
- To determine the age at which rat hearts gain the ability to be protected by PC.
Main Methods:
- Hearts from rats of various ages (4 days to adult) were subjected to different ischemic preconditioning protocols.
- Left Ventricular Developed Pressure (LVDP) recovery after prolonged ischemia and reperfusion was measured.
Main Results:
- Neonatal rat hearts (<7 days old) did not exhibit protection from PC using standard or modified protocols.
- Cardioprotection via PC was observed in hearts from 14-day-old, 21-day-old, and adult rats.
- The inability of neonatal hearts to precondition was not due to insufficient stimulus duration or excessively prolonged ischemia.
Conclusions:
- The capacity for ischemic preconditioning (PC) protection emerges after 7 days of age in rat hearts.
- Neonatal hearts (<7 days) lack the ability to precondition, irrespective of stimulus or ischemia duration.
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.