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

• Published in: Brain research 2000-03, Vol.858 (2), p.363-370
• Main Authors: Plaschke, Konstanze, Weigand, Markus A., Michel, Andre, Martin, Eike, Bardenheuer, Hubert J.
• Format: Article
• Language: English
• Subjects: Acute Disease; Adenosine Diphosphate - analysis; Adenosine Triphosphate - analysis; Animals; Biological and medical sciences; Brain Chemistry - physiology; Brain Ischemia - physiopathology; Cerebral hypoperfusion; Cerebrovascular Circulation - physiology; Disease Models, Animal; Energy metabolism; Energy Metabolism - physiology; Hypotension - physiopathology; Ischemic Preconditioning; Male; Medical sciences; Neurology; Rats; Rats, Wistar; Reperfusion Injury - physiopathology; Systemic hypotension; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)01950-8

Chronic cerebrovascular disorders are often complicated by additional temporary ischaemic insults, resulting in substantial deterioration of brain energy metabolism. In the present study, chronic limitations of oxygen supply were induced in Wistar rats by 2 weeks of permanent bilateral common carotid artery occlusion (2-vo) to initiate a `preconditioning-like' effect that protects rat brain energy metabolism against further acute systemic hypotension (15 min). Haemodynamic parameters, arterial blood gases and body temperature were monitored. Energy metabolites were determined in rat parietotemporal cerebral cortex: adenosine 5′-triphosphate (ATP), adenosine 5′-diphosphate (ADP), adenosine 5′-monophosphate (AMP), phosphocreatine (PCr), and adenosine by the high-pressure liquid chromatography (HPLC) technique and lactate spectrophotometrically. After 2 weeks, permanent 2-vo led to a significant 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 μmol/g, respectively. These changes were associated with a two-fold increase in AMP and adenosine. Acute systemic hypotension alone (non-preconditioning) reduced ATP and PCr drastically, to 0.97±0.51 and 1.76±1.23 μmol/g. Tissue concentrations of lactate, AMP, and adenosine were markedly increased, three- to five-fold, in `non-preconditioned' brain tissue. In contrast, after 2 weeks of 2-vo acute hypotension did not significantly alter the cortical energy state any further. The effects of preconditioning on tissue 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 additional ischaemic attack (`preconditioning-like' effect).