title: Ischemic preconditioning preserves end-ischemic ATP, enhancing functional recovery and coronary flow during reperfusion.
abstract: The mechanisms by which ischemic preconditioning (IPC) protects against reperfusion (RP) injury are unknown. The purpose of this study was to relate IPC to postischemic mechanical function, vascular reactivity, and bioenergetics. Isolated perfused rat hearts were randomized to two groups. Control (CTRL) hearts underwent 25 min of global, 37 degrees C ischemia and 40 min RP. IPC hearts underwent 2.5 min ischemia and 10 min RP followed by 25 min ischemia and 40 min RP (RP40). Left ventricular developed pressure (DP) and coronary flow were continuously measured. 31P NMR spectra determined phosphocreatine and ATP concentrations in parallel hearts every 5 min. Results are means +/- SEM; n = 6/group. Significance was assumed for P < 0.05 by paired (within groups) and unpaired (between groups) t test. CTRL heart DP recovered to 35 +/- 4% of preischemic (PI) DP by RP40 (P < 0.001), while IPC heart DP reached 99 +/- 4% (P = NS vs PI; P < 0.001 vs CTRL). CTRL coronary flow recovered to only 75 +/- 3% of PI (P < 0.001) by RP40. IPC coronary flow exceeded baseline during RP (RP40 = 118 +/- 3%, P < 0.001 vs CTRL; P < 0.05 vs PI). After 25 min ischemia, CTRL heart ATP fell to 40 +/- 4% of PI (P < 0.001) while the IPC group fell to only 60 +/- 4% (P < 0.05 IPC vs CTRL; P < 0.001 vs PI). IPC preserves more end-ischemic ATP compared to CTRL hearts with a resultant improvement in mechanical function during reperfusion. Only preconditioned hearts preserve the adaptive mechanism(s) responsible for postischemic vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Medical College Hospital, Division of Cardiothoracic Surgery, Philadelphia, Pennsylvania 19129.
authors.forename: L J
authors.initials: LJ
authors.lastname: Kaplan
authors.forename: C F
authors.initials: CF
authors.lastname: Bellows
authors.forename: H
authors.initials: H
authors.lastname: Blum
authors.forename: M
authors.initials: M
authors.lastname: Mitchell
authors.forename: G J
authors.initials: GJ
authors.lastname: Whitman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation; D004734:Energy Metabolism; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate