IN-VIVO UPTAKE OF [H-3] NIMODIPINE IN FOCAL CEREBRAL-ISCHEMIA - MODULATION BY HYPERGLYCEMIA

Cell membrane depolarization and tissue acidosis occur rapidly in seve rely ischemic brain. Preischemic hyperglycemia is recognized to increa se ischemic tissue acidosis and the present studies were undertaken to correlate depolarization and tissue acidosis during acute focal cereb ral ischemia and hyperglycemia. We used a dual-label autoradiography m ethod to simultaneously measure the in vivo distribution of [H-3]nimod ipine and [C-14]DMO (5,5-dimethyl-2,4-oxazolidinedione) in brain to id entify regions of ischemic depolarization and measure regional net tis sue pH. Regional cerebral blood flow (CBF) was measured in separate st udies. Measurements were made 30 minutes after combined middle cerebra l artery and ipsilateral common carotid artery occlusion in normoglyce mic and hyperglycemic rats. Tissue pH in the ischemic cortex was depre ssed to 6.76 +/- 0.11 in normoglycemic rats (n = 12) and 6.57 +/- 0.13 in hyperglycemic rats (n = 12), with significantly greater acidosis i n the hyperglycemic group (P < 0.001). In contrast the ratio of [H-3]n imodipine uptake in the ischemic cortex relative to the contralateral nonischemic cortex was significantly greater in normoglycemic (1.83 +/ - 0.45) than hyperglycemic (1.40 +/- 0.50) rats (P < 0.05), Within thi s region of ischemic cortex CBF was 31 +/- 22 mL/100 g in normoglycemi c rats (n = 8) and 33 +/- 22 mL/100 g/min in hyperglycemic rats (n = 9 ). Cerebral blood flow did not differ between these two groups in any region. Thus hyperglycemia reduced the extent of ischemic depolarizati on within the cortex during the first 30 minutes of focal cerebral isc hemia. This effect may be related to the increased tissue acidosis or to other factors that may lessen calcium influx and preserve cellular energy stores in the ischemic cortex of the hyperglycemic rats.