Impairment of cerebrovascular autoregulation by theophylline

The relationship between pressure and flow was investigated in the cerebral vascular bed during intraarterial theophylline infusion. The experiments were performed on isolated canine brains supported by a donor system, thus eliminating all secondary effects of theophylline on cerebral blood flow (i.e., changes in systemic blood pressure, respiration and extracranial blood flow). Cerebral blood flow was measured continuously as the total venous outflow of the confluence of sinuses and perfusion pressure was measured in the circle of Willis. Cerebral autoregulation was tested by varying the perfusion pressure in sudden steps. The position and shape of the pressure-flow curve during theophylline infusion differed significantly from control. Theophylline induced vasodilation and a considerable impairment of cerebral autoregulation, i.e., the independence of flow and pressure over the physiological range was lost. At a perfusion pressure of 80 mm Hg the mean decrease of cerebral resistance due to theophylline was 28%. During theophylline infusion the pressure-flow regression line of the pressure range, where control flow values remained constant, differed significantly from control regression line. Possible mechanisms of cerebral vasodilation due to theophylline are discussed with regard to the impairement of cerebral autoregulation. The ability of the brain to autoregulate therefore seems dependent upon the initial degree of vasodilation due to the myotropic action of theophylline. Metabolic effects of theophylline are probably not responsible for the impairment of cerebral autoregulation.