A method for recording effects of anti-epileptic drugs on interictal discharge in the cat's cerebral cortex. Factors determining the distribution of external carotid artery infusions.
The method utilizes infusion via the external carotid (ECA), the internal maxillary arteries and their anastomoses to the cerebral circulation. It takes into account the ipsilateral distribution of the carotid blood supply. A regular interictal epileptiform spiking from foci on both hemispheres was provided by local application to the cortical surface of small pieces of filter paper soaked in sodium benzylpenicillin, 100,000 IE ml-1. The infused drug affects the ipsilateral foci, and the contralateral one functions as a simultaneous untreated control. The stability of the interictal frequency and the effect of non-oxygen carrying solvents are described. The effect of changes in blood pressure, temperature and PCO2 are considered as well as the coupling between activity in ipsi- and contralateral foci. Experiments with infused radioactive microspheres were performed to determine the strictness of the ipsilateral distribution and the conditions under which it was upheld. With mean arterial blood pressures between 70 mm Hg and 170 mm Hg and infusion speeds between 1.0 ml min-1 and 6.3 ml min-1 the distribution to the contralateral cerebral hemisphere was 0.3% (SD 0.2, SEM 0.1). Infusions of [125I]albumin were used to determine the blood flow in ECA. The flow varied between 20 ml min-1 and 68 ml min-1. The higher values were seen when the extracerebral shunting was high. Conditions influencing the dilution of the infusion and its distribution within the brain were investigated. Important factors were carotid and cerebral blood flow, arterial blood pressure, speed and duration of the infusion, recirculation and cerebral temperature. Arterial PCO2, pH and PO2 should be carefully controlled. Computer-supported treatment of interictal spike frequency and amplitude, as well as of circulatory and respiratory parameters, was utilized. The method was tested in experiments with infusions of 5 alpha-pregnanolone. It was shown that infusions, shorter than the estimated circulation time, reduced the interictal spike frequency and amplitude recorded from the ipsilateral foci without effects on the contralateral ones.
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D002342:Carotid Artery, External; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D008722:Methods; D008863:Microspheres; D010313:Partial Pressure; D010400:Penicillin G / Q000008:administration & dosage
D000927:Anticonvulsants; D010400:Penicillin G