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

Abstract

BackgroundThis 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.MethodsFifteen 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.ResultsDifferences 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.ConclusionResults 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.

Quantitative perfusion and water transport time model from multi b-value diffusion magnetic resonance imaging validated against neutron capture microspheres

“…In comparison, standard relative perfusion requires comparison to an internal reference that is confounded if the internal reference varies. 22 However, the correlation also highlights an example of the remaining difficulty of CSF removal: partial volume contamination of CSF may falsely add to the perfusion signal at normocapnia, shown in Fig. 3(c), and lead to higher average perfusion with p < 0.05 at normocapnia, though this study does not explore this.…”

“…Note that values are considerably higher in the MCAO model due to the use of aggressive flow augmentation. 21,22 4 Discussion…”

“…Normocapnia and hypercapnia include both the left and right hemispheres, whereas occlusion and contralateral are split into corresponding hemispheres. Note that values are considerably higher in the MCAO model due to the use of aggressive flow augmentation 21 , 22 …”

“…By showing correlation to an absolute quantitative method, the work supports a method that allows absolute comparison across multiple subjects, days, and experimental groups. In comparison, standard relative perfusion requires comparison to an internal reference that is confounded if the internal reference varies 22 …”

“…Subjects were transported to the MRI suite for imaging studies within 60 min of occlusion. We evaluated experimental flow augmentation during MCAO via simultaneous administration of a vasopressor and vasodilator intended to augment CBF; 22 therefore, highly dynamic and abnormally high perfusion throughout the brain post-occlusion is expected by experimental design. Throughout the experiments, physiologic parameters were maintained within normal range (excluding PaCO2 for experiments involving intentional hypercapnia and blood pressure for experiments involving flow augmentation).…”