Preventing Hypertension After Ischemic Stroke In The Spontaneously Hypertensive Rat

Abstract

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 treating post‐stroke hypertension in the spontaneously hypertensive (SH) rat model of ischemic stroke.Male SH rats (374±9 g) were instrumented to allow the long‐term recording of BP, intracranial pressure (ICP) and brain tissue oxygen in the penumbra (pO2) via telemetry. After recording a 3‐day baseline on Day 0 an ischemic stroke was induced via a two‐hour occlusion of the middle cerebral artery (MCAo). BP was either Untreated (n= 6) or Treated (n=6) and controlled to baseline levels with the clinically‐indicated adrenergic antagonist, labetalol (0.25 mg/kg/hr sc via osmotic pump). Behavioural testing and neurological scoring (SHIRPA score) were performed on Days 1, 3, 7 and 10 to evaluate the functional recovery from stroke over time, and postmortem stroke infarct size assessed by histology on Day 10.Following a 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±26 mm3 vs Untreated 256±11 mm3).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 in rats already receiving treatment for pre‐existing hypertension, and of treatment to normotensive BP levels in SH rats to mimic the clinical situation of ‘undiagnosed pre‐existing hypertension’.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.