Acute brain death abolishes the cardioprotective effects of ischemic preconditioning in the rabbit.
BACKGROUND
Myocardial preconditioning with brief coronary artery occlusions before a sustained ischemic period is reported to reduce infarct size. We wished to evaluate whether ischemic preconditioning (IP) is efficient in an experimental brain death (BD) model in the rabbit.


METHODS
Rabbits were randomized into four experimental groups of eight animals each. In the control group (CTRL), anaesthetized rabbits were subjected to 30 min of left coronary marginal branch occlusion and 90 min of reperfusion without any pretreatment. In the CTRL+IP group, anaesthetized rabbits were preconditioned with a 3-min ischemia and 3-min reperfusion sequence before coronary occlusion. In the BD group, rabbits were subjected to 90 min of BD before 30 min of coronary occlusion and 90 min of reperfusion. In the BD+IP group, BD rabbits were preconditioned as in the CTRL+IP group before coronary occlusion. BD was induced by rapid inflation of an intracranial balloon and was validated by clinical and electroencephalographic examinations. At the termination of the experiment, left ventricular volume (LVV), myocardial volume at risk (VAR) and infarct volume (IV) were determined with methylene blue and tetrazolium staining and were measured using planimetry.


RESULTS
LW was not significantly different among the four experimental groups (CTRL, 6.54+/-0.90 cm3; CTRL+IP, 5.92+/-0.60 cm3; BD, 5.87+/-0.81 cm3; BD+IP, 6.16+/-0.95 cm3; P=ns). Furthermore, myocardial VAR, expressed as a percentage of LVV, was not significantly different between groups (CTRL, 20.0+/-4.2%; CTRL+IP, 22.32+/-2.25%; BD, 21.38+/-3.36%; BD+IP, 21.64+/-3.39%; P=NS). IV, expressed as a percentage of VAR, was significantly reduced in the CTRL+IP group compared with the CTRL group (15.76+/-8.47% vs. 49.95+/-1.51%; P<0.0001). In contrast, there was no significant difference in IV, expressed as a percentage of VAR, between the BD and the BD+IP groups (50.0+/-1.52% vs. 49.72+/-1.58%; P=NS).


CONCLUSIONS
The data indicate that the infarct-limiting effect of IP is lost in BD rabbits. Thus, the clinical potential of IP in the context of organ transplantation seems to be severely compromised.
Kirsch
M
M
Centre de Recherches Chirurgicales Henri Mondor, URA CNRS 1431, Hôpital Henri Mondor, Créteil, France.
Farhat
F
F
Garnier
J P
JP
Loisance
D
D
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D001926:Brain Death; D003331:Coronary Vessels / Q000502:physiology; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D009638:Norepinephrine / Q000097:blood; D011817:Rabbits; D013997:Time Factors; D016277:Ventricular Function, Left
D009638:Norepinephrine; D004837:Epinephrine