Research Areas

5-HT, vasospasms, and TCD

Purpose of Study: The goal of this study will be to determine if there is a link between elevated levels of 5-HT in the CSF and the development of Cerebral vasospasm as defined by transcranial doppler.

Background: Cerebrovascular Vasospasm is the most deadly complication following Subarachnoid Hemorrhage from a ruptured aneurysm or AVM. Even after the source of a Subarachnoid hemorrhage has been dealt with, the patient is still at risk of significant morbidity and mortality from this dreaded complication. There has been much research into the cause of vasospasm, but the cause of this disease is still unknown. There have been a number of agents that have been studied as a possible source, however there is currently no clear-cut cause identified. Treatment for this disease is quite limited at this time and consists mainly of increasing the patient's blood pressure in order to increase blood flow through the constricted vessels. Another agent, Nimodipine is currently used and was originally tested as a means of causing arteries to relax and dilate, however there was no evidence that this compound actually caused arteries in the head to dilate. Even though the research failed to prove that Nimodipine worked as a cerebrovascular dilator, the research did show that patients receiving this drug did have improved outcomes compared to the control groups, and the drug is still used today.

There are a number of other vasospastic diseases that have been linked with 5-hydroxytryptamine as a possible source for the spasm including Raynauds disease1,2,3, Hereditary vascular retinopathy syndrome4, scleroderma5, coronary artery spasm6, and pre-eclampsia, and eclampsia7. Raynaud's disease in particular has had numerous studies that show elevated levels of 5-HT in the blood during vasospastic periods.

Due to the association of 5-HT with other vasospastic diseases, there is a possibility that this substance also plays a large role in the development of cerebral vasospasm. If this is the case then this information could lead to further research in developing a specific 5-HT receptor blocker to counteract the effect of the 5-HT in the CSF.

Relative hypercapnia and its effect on transcranial Doppler detected vasospasms following subarachnoid hemorrhage

Purpose: To better define the effects of expired pCO2 levels on cerebral vasculature during vasospastic periods following subarachnoid hemorrhage (SAH)

Background: It is well understood that cerebral vasculature will dilate under increasing CO2 tension and constrict as CO2 levels in the cerebral spinal fluid (CSF) fall. This physiologic response was one of the cornerstones of intracranial hypertension treatment for many years until the deleterious effects of low tension CO2 on morbidity and mortality were worked out in the 1980's. This deleterious effect is caused by the vasoconstriction that occurs during falling levels of CO2 caused by severe prolonged hyperventilation. This vasoconstriction causes decreased blood flow to the brain and therefore enlarges areas of the ischemic penumbra, extending areas of ischemic damage. Current treatment of cerebral vasospasms is to optimize the perfusion pressure to the brain by increasing blood pressure and thus blood flow.

Vasospasm is a phenomenon that occurs following subarachnoid hemorrhage (SAH) due to an aneurysm or other source of arterial bleeding. The proximal vessels of the cerebral circulation seem to be the most sensitive structures in the cerebral vasculature to this type of aberration. Vasospasm causes local, discrete areas of spasm that decreases the diameter of the vessel and therefore the total flow of blood through the constricted areas. The constricted areas also cause an increase in the velocity of the blood flowing through the vessel in an attempt to keep total blood flow pumped through the vessel constant. Vasospasm is a variant of normal cerebral blood flow (CBF), and has been shown in rabbit and dog models of SAH, that although CBF is reduced vascular reactivity does remain intact (1,3) being able to once again change as the situation changes. However, some cat SAH studies demonstrate that the reactivity to hypercarbia is blunted (2), possibly allowing the blood vessel to stay dilated longer, improving vasospasms even more.

Transcranial Doppler (TCD) is used to monitor the blood velocities through major vessels in the brain that are undergoing spasm. The velocity of the blood is directly proportional to the amount of spasm, the diameter, occurring in the vessel once corrected for the blood pressure. The velocities in the Internal Carotid Artery (ICA) are used to correct for the differences in the velocities caused by changes in blood pressure. When the velocity of the blood in the cerebral vessels is corrected for the velocity of blood in the ICA the Lindegaard ratio is obtained.