The Phosphodiesterase 3 Inhibitor Cilostazol Dilates Large Cerebral Arteries in Humans Without Affecting Regional Cerebral Blood Flow

Abstract

Summary:Cilostazol, an inhibitor of phosphodiesterase (PDE) type 3, is used clinically in peripheral artery disease. PDE3 inhibitors may be clinically useful in the treatment of delayed cerebral vasospasm after subarachnoid hemorrhage. The authors present the first results on the effect of cilostazol on cerebral hemodynamics in normal participants. In this double-blind, randomized, crossover study, 200 mg cilostazol or placebo was administered orally to 12 healthy participants. Cerebral blood flow was measured using During the 4-hour observation period, there was no effect on systolic blood pressure (P ‫ס‬ 0.28), but diastolic blood pressure decreased slightly compared with placebo (P ‫ס‬ 0.04). V MCA decreased 21.5 ± 5.7% after cilostazol and 5.5 ± 12.2% after placebo (P ‫ס‬ 0.02, vs. placebo), without any change in global or regional cerebral blood flow. The superficial temporal artery diameter increased 17.6 ± 12.3% (P < 0.001 vs. baseline) and radial artery diameter increased 12.6 ± 8.6% (P < 0.001 vs. baseline). Adverse events, especially headache, were common. The findings suggest that cilostazol is an interesting candidate for future clinical trials of delayed cerebral vasospasm.

Cilostazol, an Inhibitor of Type 3 Phosphodiesterase, Produces Endothelium-Independent Vasodilation in Pressurized Rabbit Cerebral Penetrating Arterioles

“…Although the present study demonstrated that cilostazol induced vasodilation of the resistance-sized blood vessels, cilostazol was reported to have no effect on human regional cerebral blood flow [14]. This discrepancy between the in vivo and in vitro experiments may depend on (1) species differences, (2) differences of circumstances inside or surrounding the arterioles, such as existence of plasma or blood cells, changes of intracranial pressure, changes of diastolic pressure, and changes of intraluminal flow velocity, (3) changes of distribution of resistance in cerebral vasculature induced by autoregulation, and (4) relatively weak effect of cilostazol on arterioles compared with large cerebral arteries.…”

The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage

“…Cilostazol, a phosphodiesterase 3 inhibitor is a platelet aggregation inhibitor, which also has an effect on smooth muscle cells 183. Cilostazol has been shown to ameliorate vasospasm in experimental models 184.…”

A randomised, multicentre, double blind, placebo controlled trial to evaluate the efficacy and safety of cilostazol in patients with vasospastic angina

“…The mechanism is mainly explained by cerebrovascular dilatation, which occurs with other vasodilators such as nitrates, dipyridamole, sildenafil, and calcium antagonists. However, there was no withdrawal from treatment in patients receiving cilostazol due to headache 28 – 30. The haemodynamic effects of cilostazol were minimal.…”