PATHOPHYSIOLOGICAL ASSESSMENT OF NITRIC-OXIDE (GIVEN AS SODIUM-NITROPRUSSIDE) IN ACUTE ISCHEMIC STROKE

Acute ischaemic stroke is characterised by reductions in local cerebra l blood flow (CBF) and activation of circulating platelets and leucocy tes, Nitric oxide is a vasodilator and can inhibit these circulating c ells. The aim of this study was to assess the effect of nitric oxide o n platelet function and regional CBF in patients with acute ischaemic stroke. Sodium nitroprusside (SNP), a spontaneous nitric oxide donor, was administered at a dose which caused a 10 mm Hg fall in mean arteri al blood pressure (MABP) in a pathophysiological study to 22 patients with acute ischaemic stroke and 12 matched control subjects. Platelet function (whole blood aggregation and flow cytometry) was assessed bef ore and during SNP administration. Changes in regional CBF were measur ed using single photon emission computerised tomography (SPECT) scanni ng. SNP significantly reduced platelet aggregation in both the patient and control subject groups. Equally, the expression of platelet adhes ion molecules P-selectin (CD62) and glycoprotein (GP) GP IIIa (CD61) w ere significantly reduced in both groups. GP Ia (CDw49b) expression wa s significantly attenuated in the patient but not in the control group . Four patients underwent SPECT scanning and improvements in local CBF corresponding to the penumbral area of the clinical stroke site were seen in 3 of these patients. A total of 24 regions of asymmetrical per fusion were examined, pre-SNP (median (SQR)), 0.68 (0.14) vs. peri-SNP 0.78 (0.17), 2p = 0.065. SNP, given at a dose which reduced MABP by 1 0 mm Hg, significantly inhibited platelet aggregation and adhesion mol ecule expression. Improved regional CBF was seen in some patients. SNP is a candidate therapeutic agent for patients with acute ischaemic st roke and warrants further study.