gms | German Medical Science

Objective: Spreading Depolarizations (SDs) play a central role in cerebrovascular diseases. They produce secondary damage in subarachnoid hemorrhage (SAH), head trauma, intracerebral hemorrhage and ischemic stroke. The vasomotor components of SDs in humans are rarely described. SDs with vasoconstrictor components produce more brain damage. Decreasing frequency and changing the hemodynamic characteristics of SDs produce neuroprotection in lissencephalic brains. Therefore, modulation of the vasoconstrictive responses of SDs might be important for neuroprotection. We previously showed that ketamine can block 70% of SDs in patients with SAH similar to the effect seen in our swine models. Before planning a clinical trial in patients, the hemodynamic response of the SDs in gyrencephalic brains should be better characterized.

The aim of this work was first to describe the hemodynamic patterns of SDs according to their components; and second to investigate the influence of ketamine, on the vasomotor components of the hemodynamic response to SD in the swine brain.

Methods: Intrinsic optical signal imaging, as a measure of cerebral blood volume changes was used to monitor the hemodynamic changes to SDs in two different models of 20 swine in total, divided into 4 groups. In the first model, SDs were elicited by topical application of KCl; and in the second model, they occurred spontaneously after middle cerebral artery occlusion. Intervention with ketamine at a high dose of 4 mg/kg/h and 5 mg/kg/h was given in two groups.

Results: We identified four vasomotor components, two hyperemic and two oligemic, of the hemodynamic response to SD. The presence or absence, and the spatio-temporal order of this components resulted in the development of 13 different patterns, ranging from a monophasic pattern of either pure hyperemia or oligemia, to the development of more complex patterns consisting of 4 or 5 phases. The pharmacological intervention with ketamine influenced the magnitude and timing of the different vasomotor elements, and is capable of shaping the hemodynamic response to SD.

Conclusion: Identification and characterization of the diversity of hemodynamic responses to SDs and their vasomotor components are possible in a gyrencephalic swine model. This is of particular interest for the development of therapeutic options that could conteract their noxious effects when considering a clinical trial.