Permanent cerebral hypoperfusion: 'preconditioning-like' effects on rat energy metabolism towards acute systemic hypotension

Chronic cerebrovascular disorders are often complicated by additional tempo rary ischaemic insults, resulting in substantial deterioration of brain ene rgy metabolism. In the present study, chronic limitations of oxygen supply were induced in Wistar rats by 2 weeks of permanent bilateral common caroti d artery occlusion (2-vo) to initiate a 'preconditioning-like' effect that protects rat brain energy metabolism against further acute systemic hypoten sion (15 min). Haemodynamic parameters, arterial blood gases and body tempe rature were monitored. Energy metabolites were determined in rat parietotem poral cerebral cortex: adenosine 5'-triphosphate (ATP), adenosine 5'-diphos phate (ADP), adenosine 5'-monophosphate (AMP), phosphocreatine (PCr), and a denosine by the high-pressure liquid chromatography (HPLC) technique and la ctate spectrophotometrically. After 2 weeks, permanent 2-vo led to a signif icant decrease in the concentrations of cortical tissue ATP and PCr, from 3 .06 +/- 0.48 to 2.09 +/- 0.28 and from 4.27 +/- 0.63 to 3.35 +/- 0.41 mu mo l/g, respectively. These changes were associated with a two-fold increase i n AMP and adenosine. Acute systemic hypotension alone (non-preconditioning) reduced ATP and PCr drastically, to 0.97 +/- 0.51 and 1.76 +/- 1.23 mu mol /g. Tissue concentrations of lactate, AMP, and adenosine were markedly incr eased, three- to five-fold, in 'non-preconditioned' brain tissue. In contra st, after 2 weeks of 2-vo acute hypotension did not significantly alter the cortical energy state any further. The effects of preconditioning on tissu e ATP and PCr were most pronounced at 5 min and 48 h after reperfusion. In conclusion, permanent 2-vo seems to activate compensatory mechanisms, which effectively protect the rat's cortical energy metabolism against an additi onal ischaemic attack ('preconditioning-like' effect). (C) 2000 Elsevier Sc ience B.V. All rights reserved.