Pharmacological treatment of delayed cerebral ischemia and vasospasm in subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is a common and serious complication following subarachnoid hemorrhage (SAH) after ruptured cerebral aneurismal [1,2]. Although this complication is at times reversible, it may develop into a cerebral infarction [3]. DCI occurs in approximately 20% to 40% [4] of patients and is associated with increased mortality and poor prognosis [5,6]. It is usually caused by a vasospasm [7], which, although preventable, remains a major cause of poor neurological outcome and increased mortality in the course of SAH [4-6].Vasospasm is defined as a reversible narrowing of the subarachnoid arteries occurring between the third to fifth and fifteenth day after the hemorrhage, with a peak at the tenth day. It is observed in 70% of patients on angiographic scans and causes symptoms in 50% [7-10]. Angiographic vasospasm is defined as evidence of arterial narrowing compared with the parent vessels [11]. It preferentially involves the vessels of the cranial base but also may affect small-caliber vessels or diffusely the entire cerebral vascularization. The severity of vasospasm is variable. The subsequent decrease in cerebral blood flow (CBF) in the spastic arteries leads to DCI, which may develop into cerebral infarction [7,12,13].The etiology of vasospasm is complex and still poorly understood. Several factors have been shown to be involved, such as endothelial dysfunction, loss of autoregulation, and a hypovolemic component leading to a decrease in CBF [14-16]. At the acute phase, the presence of oxyhemoglobin in the subarachnoid spaces causes a local and systemic inflammatory reaction [17] with activation of platelets and coagulation [8-10]. The products derived from red blood cells (bilirubin) and endothelium (endothelin-1, free radicals) are considered to be mediators of the vasospasm [18-22] Structural anomalies in endothelial and smooth muscle cells also have been reported [23].Treatments of DCI consist of preventing or minimizing secondary injuries