Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury.
Ischemic preconditioning (IP) reduces infarct size in young animals; however, its impact on aging is underinvestigated. The effect of variations in IP stimuli was studied in young, middle-aged, and aged rat hearts. Isolated hearts underwent 35 min of regional ischemia and 120 min of reperfusion. Hearts with IP were subjected to either one ischemia-reperfusion cycle (5 min of ischemia and 5 min of reperfusion per cycle) or three successive cycles before 35 min of regional ischemia. Additional studies investigated the effects of pharmacological preconditioning in aged hearts using the adenosine A(1) receptor agonist 2-chloro-N(6)-cyclopentyladenosine, the protein kinase C analog 1,2-dioctanoyl-sn-glycerol, and the mitochondrial ATP-sensitive potassium (K(ATP))-channel opener diazoxide. Infarct sizes indicated that the aged rat heart could not be preconditioned via ischemic or pharmacological means. The middle-aged rat heart had a blunted IP response compared with the young adult (only an increased IP stimulus caused a significant reduction in infarct size). These results suggest that there are defects within the IP signaling cascade of the aged heart. Clinical relevance is important if we are to use any IP-like mimetics to the benefit of an aging population.
Schulman
D
D
Hatter Institute for Cardiovascular Studies, University College London Hospital and Medical School, WC1E 6DB, United Kingdom.
Latchman
D S
DS
Yellon
D M
DM
D000241:Adenosine / Q000031:analogs & derivatives; D000375:Aging / Q000502:physiology*; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D004075:Diglycerides; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; C044295:1,2-dioctanoylglycerol; C058394:2-chloro-N(6)cyclopentyladenosine; D000241:Adenosine; D003981:Diazoxide