Ischemic preconditioning decreases oxidative stress during reperfusion: a chemiluminescence study.
The mechanism responsible for ischemic preconditioning (IPC) is still unknown but may involve the induction of antioxidant enzymes decreasing oxidative stress during subsequent periods of ischemia (I) and reperfusion (RP). The purpose of this study was to determine whether, in fact, an antioxidant mechanism is involved in the protection afforded by IPC. Lucigenin-enhanced chemiluminescence (LEC), a direct, continuous, nondestructive, on-line method was used to monitor the net amount of free oxygen radicals (FOR) produced during perfusion of rat hearts. Isolated rat hearts were perfused inside a chemiluminescence chamber with lucigenin (1 x 10(-5) M) and subjected to either: (a) 80 min of equilibration (EQ80 group, n = 6), (b) 15 min of EQ, 2 min of IPC, 10 min of reequilibration (REQ), 25 min of I, and 28 min of RP (IPC group, n = 8), or (c) 27 min of EQ, 25 min of I, and 28 min of RP (CTRL, n = 7). Chemiluminescence was measured as counts per minute (cpm) and expressed as %EQ15 (mean +/- SEM). Paired and nonpaired t tests were used for statistical evaluation. EQ80 showed no changes in oxidative stress throughout perfusion (4.5 +/- 0.2 x 10(3) cpm at EQ15 vs 5.1 +/- 0.5 x 10(3) cpm at EQ80, P = NS). During REQ (after IPC) there was a surge of chemiluminescence in IPC hearts compared with CTRL (130 +/- 8% vs 108 +/- 4%, P < 0.05). During reperfusion there was a surge of chemiluminescence in CTRL hearts that was diminished in the IPC hearts (550 +/- 50% vs 380 +/- 50% in IPC, P < 0.05). We conclude that: (1) IPC induces an oxidative stress generating FOR during REQ, (2) IPC decreases the initial FOR burst during RP. We speculate that IPC increases cellular antioxidant defenses which result in decreased oxidative stress during early RP.
Department of Cardiothoracic Surgery, The Medical College of Pennsylvania-Hahnemann University, Presbyterian Hospital, Philadelphia 19129, USA.
J A
JA
Crestanello
D M
DM
Lingle
J
J
Kamelgard
J
J
Millili
G J
GJ
Whitman
D000166:Acridines / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008163:Luminescent Measurements; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D012039:Regional Blood Flow
D000166:Acridines; C033472:10,10'-dimethyl-9,9'-biacridinium