Cerebral vasospasm.

Established vasospasm is refractory to vasodilators, although certain agents (nimodipine or papavarine) may reverse early vasospasm when administered in high local concentrations. Calcium channel antagonists do not affect the incidence of arteriographic vasospasm and probably improve outcome by other mechanisms. Mechanical dilatation of cerebral arteries in chronic vasospasm (angioplasty) produces a long-lasting increase in arterial caliber. Prolonged exposure of cerebral arteries to perivascular blood (probably OxyHb) is necessary for the development of vasospasm. Experimental data have implicated lipid peroxidation or inflammatory responses in the pathogenesis of vasospasm. OxyHb is the most likely pathogenic agent for vasospasm, although the specific mechanism is uncertain. OxyHb causes vasoconstriction by agonist-mediated SMC contraction and catalyzes the formation of reactive oxygen species with subsequent lipid peroxidation. Morphologic changes in SMC have been consistently observed in human and experimental vasospasm. Chronic exposure to perivascular blood produces reduced vessel wall compliance and insensitivity to vasoconstrictors and vasodilators. Although endothelial damage after SAH is sufficient to stimulate only minimal SMC proliferation, the physiologic response of injured endothelium may be manifested by increased ET-1 secretion, augmented platelet adherence, and increased permeability.