VARIAZIONI INDOTTE DA FARMACI SULLO STATO ENERGETICO CEREBRALE

The evaluation of the energy state of the brain and of possible drug induced changes can be conveniently carried out through the quantification of the components of the pool of adenylates and of the measurements of the potentials of the metabolic systems related to the dehydrogenase activity, including the lactate pyruvate system. On the basis of these premises, series of experiments were performed, aimed at demonstrating functional and metabolic interactions between the following parameters: cortical flow; lactate pyruvate redox potential across the brain, as indirectly evaluated by measuring both the arterial and the venous concentrations of lactate and pyruvate; the energy charge potential, as determined by the measurement of the concentrations of ATP, ADP and AMP. On the whole, remarkable differences were found between the above mentioned parameters, with regard to a controlled experimental condition, i.e. hypoxemia in curarized beagle dogs in hypovolemic hypotension; indeed, both the cerebral flow and redox potential are subject to marked changes for values of PaO ₂ compatible with constant levels in the energy charge potential. Of the 2 drugs studied, bemegride always induced a discharge of the energy state, both under normotension and normoxia conditions, and during hypoxemia and hypovolemic hypotension, as well as during the posthypoxic recovery. This effect can be related to regional differences between energy requirements and oxygen availability, that is to say, in a state of potential hypoxia. On the contrary, nicergoline, though causing no basic changes in the energy charge under the first 2 experimental conditions described, significantly increased the ability for posthypoxic recovery. This favorable effect on recovery times is most likely related to an interference with enzymatic regulatory processes, which modulate the interconversion of the components of the pool of adenylates. (Journal received: 10 July 1974)