Dose-dependent protection of cardiac function by propofol during ischemia and early reperfusion in rats: effects on 15-F2t-isoprostane formation.
We examined the effects of propofol (2,6-diisopropylphenol) on functional recovery and 15-F2t-isoprostane generation during ischemia-reperfusion in Langendorff-perfused rat hearts. Before the induction of 40 min of global ischemia, hearts were perfused (10 min) with propofol at 5 (lo-P) or 12 microg/mL (hi-P) in saline or with saline only (control). During ischemia, saline, lo-P, or hi-P was perfused through the aorta at 60 microL/min. During the first 15 min of reperfusion, propofol (5 or 12 microg/mL) was continued, followed by perfusion with 5 microg/mL propofol for 75 min in both propofol-treated groups. After 90 min of reperfusion (Rep-90), heart tissues were harvested for assessment of antioxidant status. In hi-P, we observed increased latency to and greater reduction of ischemic contracture relative to the lo-P or control groups. 15-F2t-Isoprostane concentrations increased during ischemia and were significantly lower in hi-P and lo-P than in control (P < 0.01). At Rep-90, myocardial functional recovery was greater in both propofol-treated groups relative to control, and it correlated positively with tissue antioxidant capacity preservation. Tissue antioxidant capacity was better preserved in hi-P than in lo-P treatment (P < 0.05). We conclude that oxidant injury occurs during ischemia and reperfusion, and propofol provides dose-dependent protection primarily by enhancing tissue antioxidant capacity and reducing lipid peroxidation.
Xia
Zhengyuan
Z
Centre for Anesthesia & Analgesia, Department of Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC V6T IZ3, Canada.
Godin
David V
DV
Chang
Thomas K H
TK
Ansley
David M
DM
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes / Q000096:biosynthesis*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D018686:Anesthetics, Intravenous; D000975:Antioxidants; D028441:F2-Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D015742:Propofol