Oxyhemoglobin as the principal cause of cerebral vasospasm: a holistic view of its actions.

Abstract

While oxyhemoglobin (oxyHb) is deemed to be the principal cause of cerebral vasospasm following subarachnoid hemorrhage, the mechanism(s) whereby it leads to vasospasm is by no means clear. Of importance is the fact that prolonged contraction of arterial smooth muscle is not the sole feature of cerebral vasospasm, particularly in humans. Vasospasm is also associated with the occurrence of organic changes in the arterial wall as well as the derangement of cerebral microcirculation. These additional features may play a pivotal role when vasospasm in the proximal arteries incurs delayed ischemic neurological deficits and cerebral infarction. The question then arises as to whether or not all the features of vasospasm are attributable to the actions of oxyHb. In this regard, owing to the recent advances in vascular physiology, it has become clear that the cerebral vasculature should be regarded as an organ, not a mere conduit, in which all intracellular mechanisms are functionally integrated for the maintenance and regulation of cerebral blood flow (CBF). In the sense that the arterial function is not simply a sum of the individual cellular functions, it may be described as "holistic". According to extant literature, oxyHb has multifarious actions that can be divided into the following three categories: (1) scavenging of nitric oxide (NO), (2) generation of reactive oxygen species (ROS), (3) activation of the tyrosine kinase/mitogen-activated kinase (TK/MAPK) pathway. Based on such knowledge, the present review aims at a speculative synthesis in terms of how oxyHb pertains to the occurrence of vasospasm, in which the highly integrated, holistic mechanisms within the cerebral artery are perturbed for a prolonged period.