Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB004

Poster Communications

Preventing Hypertension after Ischemic Stroke in the Spontaneously Hypertensive Rat

P. Thakkar1, C. Barrett1, A. McGregor3, A. Barber2, J. F. Paton1,4, F. McBryde1

1. Physiology, University of Auckland, Auckland, New Zealand. 2. Centre for Brain Research, University of Auckland, Auckland, New Zealand. 3. Pharmacy, University of Otago, Dunedin, New Zealand. 4. Physiology, University of Bristol, Bristol, United Kingdom.


Over 80% of patients show a transient increase in blood pressure (BP) after ischemic stroke, regardless of their previous blood pressure level. However, whether this increased pressure is necessary to enhance or maintain oxygenation of penumbra tissues remains uncertain. We aimed to determine the impact of preventing post-stroke hypertension in the spontaneously hypertensive (SH) rat model of ischemic stroke. Male SH rats (374±9 g) were instrumented under isoflurane anaesthesia (2-3% in 100% oxygen) to allow the long-term telemetry recording of BP, intracranial pressure (ICP) and brain tissue oxygen in the penumbra (pO2). After recording a 3-day baseline, ischemic stroke was induced on Day 0 via a two-hour occlusion of the middle cerebral artery (MCAo), under anaesthesia as above. The increase in BP after stroke was either Untreated (n= 6), or Treated (n=6) and controlled to baseline levels with the clinically-indicated adrenergic antagonist, labetalol (0.25mg/kg/hr sc via osmotic pump). Neurological recovery (SHIRPA score) was assessed on Days 1, 3, 7 and 10 to evaluate the functional recovery from stroke over time, and post-mortem stroke infarct size assessed by histology on Day 10. Following stroke, BP increased rapidly in Untreated SH rats, reaching a peak of 35±3 mmHg above baseline within 24 hours. Treatment with labetalol significantly reduced BP on D0 and D1 (p<0.05), which in combination with a small increase in ICP (+3±0.8 mmHg in Untreated; +0.4±0.3 mmHg in Treated; p=0.047) on D0 resulted in a lower cerebral perfusion pressure (CPP=MAP-ICP) in Treated animals. Penumbra tissue oxygen levels were not reduced with labetalol treatment, with a small but significant elevation in pO2 seen in the treated animals in the 24 hours after stroke. Treated and Untreated rats showed a similar impairment after stroke in terms of neurological score, functional outcome and infarct volume (274±26mm3 vs Untreated 256±11mm3). Treating post-stroke hypertension does not appear to have a major impact on the functional recovery from stroke in rats with pre-existing hypertension. Future studies will examine the impact of blood pressure lowering (1) in SH rats already receiving treatment for pre-existing hypertension, and (2) treatment to normotensive BP levels after stroke in SH rats, to mimic the clinical situation of undiagnosed pre-existing hypertension.

Where applicable, experiments conform with Society ethical requirements