The purpose of this study was to angioscopically observe the process of thrombolysis after intracoronary administration of thrombolytic agents and to investigate the effects of these agents on coagulation/fibrinolysis systems in dogs. The coronary endothelium was removed and thrombus formation was confirmed by angioscopy. In the tissue plasminogen activator (tPA) group (n=8), complete thrombolysis occurred in all animals, but thrombolysis was incomplete in the urokinase (UK) group (n=6). The plasma level of plasmin alpha2-plasmin inhibitor complex peaked at 15 minutes after treatment in both the tPA and UK groups. Plasma thrombin-antithrombin III (TAT) complex decreased transiently at 15 minutes after tPA administration but increased at 30 and 60 minutes (P<0.05). In the UK group, plasma TAT also showed a transient decrease followed by an increase, which was minimal compared with that in the tPA group. Plasma TAT decreased transiently after infusion of tPA and subsequently increased to above the pretreatment level, suggesting a risk of rethrombosis after successful recanalization.

The calcitonin gene-related peptide (CGRP), a known potent intrinsic cerebral vasodilator, is contained in the sensory nerves from trigeminal ganglia that inervate the cerebral arteries. We previously reported that human alpha CGRP (hCGRP) dilates spastic cerebral arteries after experimental subarachnoid haemorrhage (SAH) in rabbits. In the present study, we investigated the prophylactic potential of a sustained higher cerebrospinal fluid level of hCGRP against experimental cerebral vasospasm. An hCGRP slow-release tablet (hCGRP s-r tablet) was developed for cisternal implantation. Experimental SAH was induced by percutaneous cisternal injection of autologous arterial blood. Angiography was initiated on day 1 (before SAH) and performed everyday. The hCGRP s-r tablet was implanted into the cisterna magna on day 2 in the treated groups. The spastic response of the basilar artery was maximized on day 4 in the non-treated (80.7% of day 1) and the placebo-treated (79.3%) groups. In contrast, the arterial diameters on day 4 were 96.1% and 90.5% of day 1 in the groups implanted with hCGRP 24 micrograms and 153 micrograms s-r tablets, respectively. We also measured the concentration of hCGRP in the cerebrospinal fluid (CSF) following implantation of the hCGRP 24 micrograms s-r tablet in the cisterna magna. The hCGRP concentration before implantation was below the dectable level. Following implantation, the hCGRP level in the CSF was 23.12 nmol/L on the second day and remained at elevated levels until the fifth day. These experiments suggest that the intrathecal single implantation of the hCGRP s-r tablet could produce an elevated concentration of hCGRP in the CSF over five days and have prevented the cerebral vasospasm after SAH in the rabbit. The hCGRP s-r tablet may be clinically applicable in the treatment of patients with SAH against cerebral vasospasm.

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1 A possible cerebroprotective effect of nicorandil was investigated in a canine model of 5 min global cerebral ischaemia, and compared with protective effects of nitroglycerin and nicardipine. 2 Cerebral ischaemia was produced by occlusion of the left subclavian and the brachiocephalic arteries with preceding ligation of the intercostal arteries. The decrease in baroreflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, was used to assess the cerebroprotective effect. kg-' min-', i.v.) were infused for 60 min just before ischaemia. Nitroglycerin and nicardipine decreased mean arterial blood pressure to an extent similar to that induced by the lower dose of nicorandil. Blood flow in the dorsal medulla oblongata was increased by nicorandil and nicardipine, but not by nitroglycerin. 4 Nicorandil at both doses and nitroglycerin prevented the post-ischaemic decrease in BRS. In these cases, bilateral vagotomy during the reperfusion period decreased BRS, indicating that the vagal component of BRS was protected from ischaemia. On the other hand, nicardipine failed to exert a cerebroprotective effect. 5 The present study suggests that nicorandil may possess a direct cerebroprotective effect and that its property as a nitrate might, at least in part, be important for the observed cerebral protection.