Endovascular Management of Cerebrovascular Disease by Dr. Ricardo A. Hanel MD PhD & Dr. Ciaran J. Powers MD PhD & Dr. Eric Sauvageau MD

Author:Dr. Ricardo A. Hanel, MD, PhD & Dr. Ciaran J. Powers, MD, PhD & Dr. Eric Sauvageau, MD
Language: eng
Format: epub
ISBN: 9780323311854
Publisher: Elsevier
Published: 2014-09-15T00:00:00+00:00

Ryanodine

Ryanodine receptors (RyRs) are a class of calcium release channels located at the endoplasmic reticulum that regulate luminal calcium concentration by mediating calcium-induced calcium release. There are 3 subtypes present in vascular smooth muscle (RyR1, RyR2, and RyR3).35,36 RyRs are involved in regulating cerebral artery luminal diameter,37,38 and RyRs, especially RyR1, are associated with symptomatic vasospasm after SAH. In a pilot gene association study of 46 patients, Rueffert and colleagues39 found that SAH patients who were heterozygous carriers for the G>T genotype of RyR1 c.6178G>T polymorphism had an increased risk of developing symptomatic vasospasm (OR 6.4; 95% CI, 1.1%–37.8%; P = .04) compared with C>T or G>A. In the patients without vasospasm (n = 30), there were only 6.7% G>T carriers (P = .04). In the patients with symptomatic vasospasm (n = 16), 31.3% carried the c.6178G>T polymorphism. In the 7 patients who were heterozygous for G>T, 5 (71.4%) developed symptomatic vasospasm: 3 died due to severe complications from vasospasm, 1 survived with serious disability, and 1 survived with moderate recovery. The other 2 patients with c.6178G>T polymorphism had no symptomatic vasospasm.

Further evidence implicating RyR1 in vasospasm is found in studies using RyR1 antagonists. Dantrolene, a specific RyR1 antagonist, may prevent cerebral vasoconstriction in basilar and femoral arteries in rats40 and has been shown to reduce vasoconstriction after dantrolene infusion in 3 human patients as measured by TCD velocities.41

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