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Augmentation of perfusion with simultaneous vasodilator and inotropic agents in experimental acute middle cerebral artery occlusion: a pilot study


Background This study tests the hypothesis that simultaneous cerebral blood pressure elevation and potent vasodilation augments perfusion to ischemic tissue in acute ischemic stroke and it varies by degree of pial collateral recruitment.

Methods Fifteen mongrel canines were included. Subjects underwent permanent middle cerebral artery occlusion; pial collateral recruitment was scored before treatment. Seven treatment subjects received a continuous infusion of norepinephrine (0.1–1.52 µg/kg/min; titrated 25–45 mmHg above baseline mean arterial pressure while keeping systolic blood pressure below 180 mmHg) and hydralazine (20 mg) starting 30 min post-occlusion. Perfusion (cerebral blood flow—CBF) was evaluated with quantitative dynamic susceptibility contrast MRI 2.5 hours post-occlusion to produce images in mL/100 g/min, and relative CBF measured as ratios. Mean region of interest (ROI) values were reported, and compared and subject to regression analysis to elucidate trends.

Results Differences in quantitative CBF (qCBF) between treatment and control group varied by degree of pial collateral recruitment, based on Wilcoxon rank sum scores and regression model fit. For poorly collateralized subjects, ipsilateral anatomic, core infarct, and penumbra regions showed treatment with higher qCBF, raised above the ischemic threshold, compared with the control, while well collateralized subjects showed a paradoxical decrease maintained above the ischemic threshold for neuronal death. qCBF on the contralateral side increased regardless of collateralization.

Conclusion Results suggest that perfusion can be augmented in ischemic stroke with norepinephrine and hydralazine. Perfusion augmentation depends on degree of collateralization and territory in question, with some evidence of vascular steal.

  • MRI
  • Angiography
  • Brain
  • Stroke

Data availability statement

Data are available upon reasonable request.

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