Augmenting collateral blood flow during ischemic stroke via transient aortic occlusion.
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ABSTRACT:
SUBMITTER: Winship IR
PROVIDER: S-EPMC3887343 | biostudies-other | 2014 Jan
REPOSITORIES: biostudies-other
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Project description:Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P<0.001) and smaller baseline diffusion lesion volume (Rho -0.70, P<0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute (P=0.02) and relative (P<0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho -0.68, P<0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute (P=0.003) and relative (P=0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.
| S-EPMC3734777 | biostudies-literature
Project description:Background and purposeCollateral flow in acute ischemic stroke is known as a predictor of treatment outcome and long-term prognosis. However, factors determining the initial collateral flow remain unclear. We investigated factors related to collateral flow in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and further analyzed the results according to stroke etiology.MethodsThis was a retrospective study using prospective stroke registry data from a single university hospital from October 2014 to May 2021. AIS-LVO with middle cerebral artery M1 occlusion identified by pre-treatment multiphasic computed tomography angiography was included. Collateral flow score was graded on a 6-point ordinal scale according to pial arterial filling.ResultsA total of 74 patients [cardioembolism (CE): 57; large artery atherosclerosis (LAA): 17] was included. The mean age of all patients was 72.2 ± 11.7 years, and 37.8 % (n = 28) were men. Multivariate regression analysis showed that initial SBP [odds ratio (OR): 0.994; 95% confidence interval (CI): 0.990-0.998; p = 0.002] and stroke etiology (OR: 0.718; 95% CI: 0.548-0.940; p = 0.019) were independent factors of the collateral flow grade. Collateral flow grade was independently associated with initial SBP in the CE group (OR: 0.993; 95% CI: 0.989-0.998; p = 0.004) but not in the LAA group (OR: 0.992; 95% CI: 0.980-1.004; p = 0.218). Initial SBP was significantly correlated with NIHSS score in the CE group but not in the LAA group (r 2= 0.091, p = 0.023; r 2 = 0.043, p = 0.426, respectively).ConclusionsElevated initial SBP was associated with poor cerebral collateral flow and more severe symptoms in the CE group, but not in the LAA group in patients with AIS-LVO. These findings suggest differential effects of initial SBP elevation on collateral flow by stroke subtypes.
| S-EPMC9136006 | biostudies-literature
Project description:Background and purposeCollaterals sustain the penumbra before recanalization and offset infarct growth, yet the influence of baseline collateral flow on recanalization after endovascular therapy remains relatively unexplored.MethodsWe analyzed consecutive patients who received endovascular therapy for acute cerebral ischemia from 2 distinct study populations. We assessed the relationship between pretreatment collateral grade and vascular recanalization (Thrombolysis In Myocardial Ischemia [TIMI] scale). In addition, we assessed infarct growth on serial MRI.ResultsA total of 222 patients was included, 138 from the United States and 84 from South Korea. Complete revascularization occurred in 14.1% (11 of 78) patients with poor pretreatment collateral grades, whereas it was observed in 25.2% (26 of 103) patients with good collaterals and 41.5% (17 of 41) patients with excellent collaterals (P<0.001). This relationship was consistently observed in both study populations, although the mode of endovascular therapy was different between them. After adjustment for other factors, including mode of endovascular therapy, prior use of intravenous tissue plasminogen activator, and site of occlusion, pretreatment collateral grade was independently associated with recanalization. When revascularization was achieved, greater infarct growth occurred in patients with poor collaterals than in those with good collaterals (P=0.012).ConclusionsOur data indicate that angiographic collateral grade determines the recanalization rate after endovascular revascularization therapy. When therapeutic revascularization was achieved, beneficial effects were not observed in patients with poor collaterals. Angiographic collateral grade may therefore help guide treatment decision-making in acute cerebral ischemia.
| S-EPMC3051344 | biostudies-literature
Project description:Background and purposeCollateral blood supply is a key determinant of outcome in large-vessel occlusion acute ischemic stroke. Single- and multiphase CTA collateral scoring systems have been described but are subjective and require training. We aimed to test whether the CTP-derived hypoperfusion intensity ratio is associated with CTA collateral status and whether a threshold hypoperfusion intensity ratio exists that predicts poor CTA collaterals.Materials and methodsImaging and clinical data of consecutive patients with large-vessel occlusion acute ischemic stroke were retrospectively reviewed. Single-phase CTA and multiphase CTA scoring were performed by 2 blinded neuroradiologists using the Tan, Maas, and Calgary/Menon methods. CTP was processed using RApid processing of PerfusIon and Diffusion software (RAPID). Hypoperfusion intensity ratio = ratio of brain volume with time-to-maximum >10 seconds over time-to-maximum >6-second volume. Correlation between the hypoperfusion intensity ratio and CTA collateral scores was calculated using the Pearson correlation. The optimal threshold of the hypoperfusion intensity ratio for predicting poor collaterals was determined using receiver operating characteristic curve analysis.ResultsFifty-two patients with large-vessel occlusion acute ischemic stroke were included. Multiphase CTA collateral scoring showed better interrater agreement (κ = 0.813) than single-phase CTA (Tan, κ = 0.587; Maas, κ = 0.273). The hypoperfusion intensity ratio correlated with CTA collateral scores (multiphase CTA: r = -0.55; 95% CI, -0.67 to -0.40; P ≤ .001). The optimal threshold for predicting poor multiphase CTA collateral status was a hypoperfusion intensity ratio of >0.45 (sensitivity = 78%; specificity = 76%; area under the curve = 0.86). Patients with high hypoperfusion intensity ratio/poor collateral status had lower ASPECTS/larger infarcts, higher NIHSS scores, and larger hypoperfused volumes.ConclusionsThe hypoperfusion intensity ratio is associated with CTA collateral status in patients with large-vessel occlusion acute ischemic stroke. The hypoperfusion intensity ratio is an automated and quantitative alternative to CTA collateral scoring methods for both clinical and future stroke trial settings.
| S-EPMC8367626 | biostudies-literature
Project description:Background: Neurovascular coupling enables a rapid adaptation of cerebral blood flow (CBF) to support neuronal activities. Whether this mechanism is compromised during the acute phase after ischemic stroke remains unknown. In this study, we applied a phase-amplitude cross-frequency coupling (PAC) algorithm to investigate multimodal neuro signals including CBF velocity (CBFV), and electroencephalography (EEG). Methods: Acute ischemic stroke patients admitted to the Neurointensive Care Unit, Tiantan Hospital, Capital Medical University (Beijing, China) with continuous monitoring of 8-lead EEG (F3-C3, T3-P3, P3-O1, F4-C4, T4-P4, P4-O2), non-invasive arterial blood pressure (ABP), and bilateral CBFV of the middle cerebral arteries or posterior cerebral arteries were retrospectively analyzed. PAC was calculated between the phase of CBFV in frequency bands (0-0.05 and 0.05-0.15 Hz) and the EEG amplitude in five bands (δ, θ, α, β, γ). The global PAC was calculated as the sum of all PACs across the six EEG channels and five EEG bands for each patient. The hemispherical asymmetry of cross-frequency coupling (CFC) was calculated as the difference between left and right PAC. Results: Sixteen patients (3 males) met our inclusion criteria. Their age was 60.9 ± 7.9 years old. The mean ABP, mean left CBFV, and mean right CBFV were 90.2 ± 31.2 mmHg, 57.3 ± 20.6 cm/s, and 68.4 ± 20.9 cm/s, respectively. The PAC between CBFV and EEG was significantly higher in β and γ bands than in the other three bands. Occipital region (P3-O1 and P4-O2 channels) showed stronger PAC than the other regions. The deceased group tended to have smaller global PAC than the survival group (the area under the receiver operating characteristic curve [AUROC] was 0.81, p = 0.57). The unfavorable outcome group showed smaller global PAC than the favorable group (AUROC = 0.65, p = 0.23). The PAC asymmetry between the two brain hemispheres correlates with the degree of stenosis in stroke patients (p = 0.01). Conclusion: We showed that CBFV interacts with EEG in β and γ bands through a phase-amplitude CFC relationship, with the strongest PAC found in the occipital region and that the degree of hemispherical asymmetry of CFC correlates with the degree of stenosis.
| S-EPMC6422917 | biostudies-literature
Project description:Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury.
| S-EPMC5221807 | biostudies-literature
Project description:Background and purposeCollateral blood flow is an important prognostic marker in the acute stroke situation but approaches for assessment vary widely. Our aim was to compare strategies of collateral blood flow assessment in dynamic and conventional CTA in their ability to predict the follow-up infarction volume.Materials and methodsWe retrospectively included all patients with an M1 occlusion from an existing cohort of 1912 consecutive patients who underwent initial multimodal stroke CT and follow-up MR imaging or nonenhanced CT. Collateralization was assessed in both conventional CT angiography and dynamic CT angiography by using 3 different collateral grading scores and segmentation of the volume of hypoattenuation. Arterial, arteriovenous, and venous phases were reconstructed for dynamic CT angiography, and all collateral scores and the volume of hypoattenuation were individually assessed for all phases. Different grading systems were compared by using the Bayesian information criterion calculated for multivariate regression analyses (Bayesian information criterion difference = 2-6, "positive"; Bayesian information criterion difference = 6-10, "strong"; Bayesian information criterion difference = >10, "very strong").ResultsOne hundred thirty-six patients (mean age, 70.4 years; male sex, 41.2%) were included. In the multivariate analysis, models containing the volume of hypoattenuation showed a significantly better model fit than models containing any of the 3 collateral grading scores in conventional CT angiography (Bayesian information criterion difference = >10) and dynamic CT angiography (Bayesian information criterion difference = >10). All grading systems showed the best model fit in the arteriovenous phase. For the volume of hypoattenuation, model fit was significantly higher for models containing the volume of hypoattenuation as assessed in the arteriovenous phase of dynamic CT angiography compared with the venous phase (Bayesian information criterion difference = 6.2) and the arterial phase of dynamic CT angiography (Bayesian information criterion difference = >10) and in comparison with conventional CT angiography (Bayesian information criterion difference = >10).ConclusionsThe use of dynamic CT angiography within the arteriovenous phase by using quantification of the volume of hypoattenuation is the superior technique for assessment of collateralization among the tested approaches.
| S-EPMC8013068 | biostudies-literature
Project description:IntroductionPeripheral arterial disease (PAD) is a major risk factor for lower-extremity amputation in diabetic patients. Unfortunately, previous clinical studies investigating therapeutic angiogenesis using the vascular endothelial growth factor (VEGF) have shown disappointing results in diabetic patients, which evokes the necessity for novel therapeutic agents. The apelinergic system (APJ receptor/apelin) is highly upregulated under hypoxic condition and acts as an activator of angiogenesis. Apelin treatment improves revascularization in nondiabetic models of ischemia, however, its role on angiogenesis in diabetic conditions remains poorly investigated. This study explored the impact of Pyr-apelin-13 in endothelial cell function and diabetic mouse model of hindlimb ischemia.MethodsNondiabetic and diabetic mice underwent femoral artery ligation to induce limb ischemia. Diabetic mice were implanted subcutaneously with osmotic pumps delivering Pyr-apelin-13 for 28 days. Blood flow reperfusion was measured for 4 weeks post-surgery and exercise willingness was assessed with voluntary wheels. In vitro, bovine aortic endothelial cells (BAECs) were exposed to normal (NG) or high glucose (HG) levels and hypoxia. Cell migration, proliferation and tube formation assays were performed following either VEGF or Pyr-apelin-13 stimulation.Results and discussionFollowing limb ischemia, blood flow reperfusion, functional recovery of the limb and vascular density were improved in diabetic mice receiving Pyr-apelin-13 compared to untreated diabetic mice. In cultured BAECs, exposure to HG concentrations and hypoxia reduced VEGF proangiogenic actions, whereas apelin proangiogenic effects remained unaltered. Pyr-apelin-13 induced its proangiogenic actions through Akt/AMPK/eNOS and RhoA/ROCK signaling pathways under both NG or HG concentrations and hypoxia exposure. Our results identified the apelinergic system as a potential therapeutic target for angiogenic therapy in diabetic patients with PAD.
| S-EPMC10450936 | biostudies-literature
Project description:BackgroundPatients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.MethodsIn this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.ResultsBy 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).ConclusionsIn this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).
| S-EPMC4887756 | biostudies-literature
Project description:BackgroundIntravenous levosimendan is indicated for acute heart failure. The compound has shown promising beneficial effects in ischemic stroke models.ObjectiveWe evaluated the efficacy and safety of oral levosimendan in patients with a history of cerebral ischemia.MethodsIn a randomized, double-blind, placebo-controlled, parallel-group study, 16 patients with a history of ischemic stroke/transient ischemic attack received oral levosimendan in 5 escalating doses from 0.125 to 2.0 mg daily for 18-day intervals of each dose; 5 patients received placebo. Twenty-four-hour ambulatory ECG and cerebral blood flow velocities using transcranial Doppler ultrasound were recorded at baseline and at the end of each dosing period. Vasomotor reactivity was assessed via the breath holding index. In addition, plasma levels of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and the metabolites of levosimendan were determined.ResultsLevosimendan induced an increase in cerebral blood flow velocities and a decrease in NT-pro-BNP compared with placebo. There was no significant effect on breath holding index. Doses ≥0.5 mg increased heart rate by 5 to 9 beats/min. The dose level of 2.0 mg exceeded the preset safety margin of ventricular extrasystoles per hour (ie, upper 90% CI of the ratio of levosimendan to placebo above 2) with an estimate of 3.10 (90% CI, 0.95-10.07).ConclusionsOral levosimendan increases cerebral blood flow velocities and diminishes NT-pro-BNP levels in patients with earlier ischemic cerebrovascular event. Daily doses up to 1.0 mg were well tolerated, whereas the 2.0 mg dose level induced an increase in ventricular extrasystoles. ClinicalTrials.gov identifier: NCT00698763.
| S-EPMC4461857 | biostudies-literature