Influence of simultaneous pressor and vasodilatory agents on the evolution of infarct growth in experimental acute middle cerebral artery occlusion

• Published in: Journal of neurointerventional surgery Vol. 13; no. 8; pp. 741 - 745
• Main Authors: Saadat, Niloufar, Christoforidis, Gregory A, Jeong, Yong Ik, Liu, Mira, Dimov, Alexey, Roth, Steven, Niekrasz, Marek, Ansari, Sameer A, Carroll, Timothy
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.08.2021
• Subjects: Animal welfare; Animals; Blood pressure; Collateral Circulation - drug effects; Diffusion Magnetic Resonance Imaging - methods; Dogs; Drug Therapy, Combination - methods; Hydralazine - pharmacology; Infarction, Middle Cerebral Artery - diagnostic imaging; Infarction, Middle Cerebral Artery - physiopathology; Ischemic Stroke - diagnostic imaging; Ischemic Stroke - physiopathology; Laboratory animals; Magnetic Resonance Angiography - methods; Magnetic resonance imaging; Medical imaging; Norepinephrine - pharmacology; Regression analysis; Treatment Outcome; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology; Veins & arteries; United States > US; brain; MRI; stroke; angiography
• ISSN: 1759-8478; 1759-8486; 1759-8486
• DOI: 10.1136/neurintsurg-2020-016539

BackgroundThis study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke.MethodsTwenty mongrel canines (20–30 kg) underwent permanent middle cerebral artery occlusion (MCAO). Eight subjects received continuous infusion of norepinephrine (0.1–1.5200 µg/kg/min; titrated to a median of 34 mmHg above baseline mean arterial pressure) and hydralazine (20 mg) starting 30 min following MCAO. Pial collateral recruitment was scored prior to treatment and used to predict infarct volume based on a previously reported parameterization. Serial diffusion magnetic resonance imaging (MRI) acquisitions tracked infarct volumes over a 4-hour time frame. Infarct volumes and infarct volume growth between treatment and control groups were compared with each other and to predicted values. Fluid-attenuated inversion recovery (FLAIR) MRI, susceptibility weighted imaging (SWI), and necropsy findings were included in the evaluation.ResultsDifferences between treatment and control group varied by pial collateral recruitment based on indicator-variable regression effects analysis with interaction confirmed by regression model fit. Benefit in treatment group was only in subjects with poor collaterals which had 35.7% less infarct volume growth (P=0.0008; ANOVA) relative to controls. Measured infarct growth was significantly lower than predicted by the model (linear regression partial F-test, slope P<0.001, intercept=0.003). There was no evidence for cerebral hemorrhage or posterior reversible encephalopathy syndrome.ConclusionOur results indicate that a combination of norepinephrine and hydralazine administered in the acute phase of ischemic stroke mitigates infarct evolution in subjects with poor but not good collateral recruitment.