Propofol enhances ischemic tolerance of middle-aged rat hearts: effects on 15-F(2t)-isoprostane formation and tissue antioxidant capacity.
OBJECTIVE
Experimental study has shown that myocardial ischemic tolerance is reduced during middle-age. We investigated the effect of propofol on ischemic tolerance of middle-aged rat hearts.


METHODS
Hearts of young adult (10 weeks old, Y) and middle-aged rats (20 weeks old, M) were assigned to propofol (P-Y, P-M) and control (C-Y, C-M) groups (n=6 each). Hearts were perfused using a Langendorff preparation with Krebs-Henseleit solution (KH) at constant flow rates. We applied propofol (P-Y, P-M) for 10 min at 12 microg/ml before inducing 40 min global ischemia. During ischemia, saline (C-Y, C-M) or propofol (P-Y, P-M) in saline was perfused through the aorta at 60 microl/min. Propofol in KH was perfused at 12 microg/ml for the first 15 min of reperfusion and subsequently reduced to 5 microg/ml in propofol treatment groups. Coronary effluent was assayed for 15-F(2t)-isoprostane after equilibration, during ischemia (T(1)) and at 0.5 (T(2)) and 5 (T(3)) min of reperfusion. After 90 min of reperfusion (T(4)), hearts were harvested to assess tissue antioxidant capacity.


RESULTS
In P-Y, we observed an increased latency to ischemic-contracture and a significantly reduced contracture after 35 min ischemia compared to control groups. No ischemic contracture was observed in P-M. There were significantly lower 15-F(2t)-isoprostane levels in P-M and P-Y than in C-M and C-Y at T(1). At T(4), the recovery of left ventricular developed pressure in P-M was greater than in P-Y (P<0.05); both were greater than in C-M and C-Y.


CONCLUSIONS
Propofol enhanced ischemic tolerance of middle-aged hearts, primarily by inhibiting lipid peroxidation.
Xia
Zhengyuan
Z
Centre for Anesthesia and Analgesia, Department of Pharmacology and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Godin
David V
DV
Ansley
David M
DM
D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D004198:Disease Susceptibility; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010477:Perfusion; D015742:Propofol / Q000378:metabolism / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000975:Antioxidants; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D020122:tert-Butylhydroperoxide; D015742:Propofol