Hypothesis related to the regulation of inducible nitric oxide synthase during carotid endarterectomy.

Sudden occlusion of an artery caused by a thrombus or emboli is the most frequent cause of acute brain ischemia (ABI). Carotid endarterectomy (CEA) represents the gold standard for preventing strokes of carotid origin. However, neuronal damage caused by ischemia and/or reperfusion may contribute to a poor clinical outcome after CEA. In response to shear stress caused by hypoxic-ischemic conditions in patients undergoing CEA, stimulation of the hypothalamic-pituitaryadrenal axis leads to biological responses known as hypermetabolic stress, characterized by hemodynamic, metabolic, inflammatory and immunological changes. These changes maintain homeostasis and assist recovery, but an unregulated inflammatory response could lead to further tissue damage and death of neurons. Nitric oxide (NO) is an important signaling molecule involved in several physiological and pathological processes, including ABI. However, an excess of NO could have detrimental effects. We hypothesized that the hypoxic-ischemic state induced by carotid clamping leads to overexpression of inducible NO synthase and that uncontrolled production of NO could adversely affect outcome after CEA.