Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbit

Objective: Brain death (BD) abolishes the infarct-limiting effect of ischem ic preconditioning (IP) in rabbits. We wished to define the role of the nor epinephrine storm in this observation. Methods: Rabbits were randomized int o six groups of ten animals each. In control group (CTRL), anaesthetized ra bbits were subjected to 30 min left coronary marginal branch occlusion and 90 min reperfusion. In CTRL + IP group, anaesthetized rabbits were precondi tioned with a 5-min ischemia and 5-min reperfusion sequence before coronary occlusion. In CTRL + NE + IP group, anaesthetized rabbits received a 10 mu g/kg norepinephrine injection 90 min before IP. In BD group, rabbits were s ubjected to 90 min of BD before coronary occlusion. In BD + IP group, brain -dead rabbits were preconditioned before coronary occlusion. In BD + LA + I P group, rabbits received an intra-arterial bolus injection of an alpha and beta adrenoreceptor blocking agent (labetolol, 1 mg/kg) prior to brain dea th induction and subsequent preconditioning. BD was induced by rapid inflat ion of an intracranial balloon. At termination of the experiment, left vent ricular volume (LVV), myocardial volume at risk (VAR) and infarct volume (I V) were determined with methylene blue and tetrazolium staining, and measur ed using planimetry. Results: LVV was not significantly different among gro ups. Myocardial VAR/LVV was not significantly different between groups (CTR L, 22.5 +/- 6.9%; CTRL + IP, 23.3 +/- 2.2%; CTRL + NE + IP, 25.9 +/- 12.7%; BD, 19.9 +/- 4.8%; BD + IP, 21.7 +/- 3.1%; BD + LA + IP, 23.4 +/- 5.8%; P = NS). IV/VAR was significantly reduced in the CTRL + IP group as compared with CTRL and CTR + NE + IP groups (12.2 +/- 1.2 vs. 49.7 +/- 1.7 and 49.3 +/- 4.7%; P < 0.0001). There was no significant difference in IV/VAR betwee n BD and BD + IP groups. In contrast, IV/VAR was reduced in BD + LA + IP co mpared to BD and BD + IP groups (13.9 <plus/minus> 5.4 vs. 50.0 +/- 1.4 and 49.6 +/- 1.5%; P < 0.001). Conclusion: The loss of infarct-limiting effect of IP in brain-dead rabbits is related to the massive release of norepinep hrine that occurs as a consequence of BD. <(c)> 2001 Elsevier Science B.V. All rights reserved.