Brain metabolic and ionic responses to global brain ischemia in the newborn dog in vivo: 1. Methodological aspects

A variety of methods has been used in order to obtain a state of acute cere bral ischemia. Most of these methods suffered from drawbacks such as irreve rsible ischemia, difficult to obtain total ischemia and heart injury. The a im of this study was to develop a new method for induction of global or par tial cerebral ischemia in the newborn dog at various post-natal ages. A mul ti-parameter monitoring system (MPA) measures the metabolic (mitochondria N ADH oxidation/reduction state), hemodynamic (reflectance), ionic (extracell ular potassium and calcium) and electrical changes (ECoG) continuously and simultaneously in the puppy's brain in vivo. A hole uas made in the chest c avity, the two large arteries supplying blood to the brain, the brachioceph alic and the subclavian arteries (B+S) were isolated and occluded during th e monitoring. In most of the animals, occlusion of these two arteries alone resulted in partial ischemia. For obtaining 100% ischemia, rye occluded bo th the B + S arteries as well as the aortic arch. Immediately at the onset of ischemia, an increase (reduction) of NADH begins. During complete ischem ia the average time until maximal increase was 4 min, compared to ischemia of up to 50% of the maximal reduction of the NADH where the average time wa s I min. After reperfusion of the brain, mitochondria recovery was very rap id and the average time until return of this parameter to its pre-ischemic level was 1.4 +/- 0.2 min. The ionic changes which occurred immediately upo n the onset of ischemia were the accumulation of extracellular potassium io ns was recorded. The rate of potassium ion accumulation was dependent on th e severity of the ischemia (range 0.19 +/- 0.08-2.2 +/- 0.4 mM min(-1)). Th e increase in the extracellular potassium ion concentration occurs in two s tages, an initial slow stage and a second rapid stage (13.0 +/- 1.8 mM). Th e results presented in this paper suggest and prove the usefulness of a new approach for global and partial ischemia in the newborn dogs. In addition, our results assess the brain metabolic, ionic, hemodynamic and electrical responses to brain ischemia in the puppies.