DIHYDROPYRIDINE LIGAND-BINDING DECREASES EARLIER IN ADOLESCENT THAN IN INFANT SWINE AFTER GLOBAL CEREBRAL-ISCHEMIA

Background and Purpose Voltage-dependent calcium channels (VDCCs) are thought to play a major role in the alteration of calcium homeostasis during ischemia. Tissue functional state as well as responsiveness to therapy with calcium channel blockers may be a function of regional ch anges in the density of VDCCs. This study determined whether VDCCs are altered by global ischemia in infant and adolescent swine. Methods We employed the radioligand (3)HPN200-110 to quantify the binding charac teristics of VDCCs in cerebral cortex caudate, and hippocampus by equi librium binding analysis. Adolescent and infant pigs underwent 3, 5, 1 0, and 20 minutes of global cerebral ischemia without reperfusion by l igation of the brachiocephalic and left subclavian arteries combined w ith hypotension to a mean arterial blood pressure of 50 mm Hg. Brain c ortex, hippocampus, and caudate samples were taken during ischemia and frozen immediately in liquid nitrogen, and crude synaptosomal membran es were isolated by differential centrifugation/filtration. (3)HPN200- 110 equilibrium binding assays were performed in the presence or absen ce of 1.0 mu mol/L unlabeled nitrendipine to determine total and nonsp ecific binding. Results Infant cortex maximal binding (B-max) increase d to 176% of control after 5 minutes of global cerebral ischemia and r emained significantly elevated (172% of control) after 10 minutes befo re falling to near control levels by 20 minutes. Adolescent cortex B-m ax increased to 157% of control levels after 5 minutes but did not rem ain elevated, falling to 131% of control by 10 minutes and near contro l by 20 minutes. Infant caudate and hippocampus binding were significa ntly elevated after 10 (124% and 149% of control, respectively) and 20 (115% and 120% of control, respectively) minutes of ischemia. Adolesc ent caudate and hippocampus binding was either not significantly diffe rent from control levels (hippocampus at 10 minutes) or less than cont rol after 10 and 20 minutes of global cerebral ischemia. The decrease in binding following the initial upregulation, which appeared earlier in the adolescent than the infant pigs, may indicate decreased toleran ce to ischemia in the adolescent. Conclusions The binding of (3)HPN200 -110 in brain is altered during 20 minutes of global cerebral ischemia , and these changes are region- and age-dependent.