Melissa Trotman-Lucas, PhD, BSc
@TroLucaM
Sudden increased blood pressure (BP), known as hypertension, following an ischaemic insult is the scenario for ~80% of acute ischaemic stroke (AIS) patients. This poststroke hypertension is the subject of continued scientific debate, with both the mechanism and its therapeutic relevance still poorly understood. There are two potential sides to the role of poststroke hypertension in AIS tissue damage: exacerbation and protection. Exacerbation of damage to vulnerable ischemic tissue may occur alongside promotion of edema formation; moreover, this abrupt increase in BP can increase the risk of cardiovascular events, including further strokes and heart attacks. On the flip side, this increased BP may be a reaction by the body to increase blood supply to the brain tissue, increasing oxygenation of the penumbral tissue. Therefore, creating the conundrum that treatment to reduce BP levels in AIS may be protective but, on the other hand, it may also escalate tissue damage and increase the risk of a poorer patient outcome.
A recent study by Thakkar et al., published in Stroke, sought to answer whether a neurally mediated increase in systemic BP protects cerebral perfusion by opposing the increase in intracranial pressure (ICP) through increasing supply pressure to the tissues. Undertaking this by characterising the cerebrovascular, ICP and cerebral oxygenation responses in a rat AIS model. Testing also the physiological impact of hypertension prevention on the maintenance of oxygenation in the penumbra and on functional recovery poststroke.
The study confirmed a significant and sudden elevation of BP immediately following AIS, providing evidence that this is likely sympathetically mediated, in part, realised by the approach used by the group. This approach allowed high temporal resolution of multiple simultaneous measurements reporting increases in both BP and sympathetic activity within seconds of AIS onset alongside the reduction in cerebral oxygen levels expected with ischaemia. The group found that, contrary to their hypothesis, poststroke hypertension was not secondary to poststroke ICP increase, refuting the suggestion that poststroke hypertension is a compensatory response to maintain supply pressure to the brain. However, they observed that cerebral perfusion pressure (CPP) increased following stroke onset while penumbra tissue oxygenation was maintained comparable to baseline, supporting the suggestion that poststroke hypertension may play a role in preserving blood flow to the penumbral area. Although treatment to reduce BP did not alter penumbral oxygenation, the authors discuss the possible role the drug nifedipine plays in maintaining cerebral blood flow despite reducing systemic BP. The rapidity of changes shown in the paper suggests that poststroke hypertension is likely to be directly linked to the hypoperfusion of ischaemia itself. The authors constructively discuss the possible mechanisms involved in this rapid communication, discussing the roles tissue oxygen, ischaemia markers and chemo-distress signals may play. Furthermore, due to the persistence of the rise in BP and sympathetic nerve activity for 2 days post ischemia, the authors also discuss the role of hormonal system involvement in the maintenance of increased BP poststroke.
In conclusion, the study reports that reducing poststroke hypertension with treatment of nifedipine does not appear to impact the ability of both the cardiovascular and cerebrovascular systems to provide adequate blood flow to the penumbra following AIS. The paper reports that reducing the acute increase in BP did not have a detrimental effect on infarct volume nor functional recovery. Importantly, the group highlights that these findings are from young normotensive male rats, emphasising that the impact of additional factors such as comorbidities and age must be explored clearly in future studies. With the increased risk factors associated with the sudden onset and severity of poststroke hypertension in patients, the findings reported here go some way towards deciphering the function of this BP increase and its role in stroke outcome.
