Degree Of Collateral Flow Research Articles

Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV

We present an annotated dataset for the purposes of creating a benchmark in Artificial Intelligence for automated clot detection. While there are commercial tools available for automated clot detection on computed tomographic (CT) angiographs, they have not been compared in a standardized manner whereby accuracy is reported on a publicly available benchmark dataset. Furthermore, there are known difficulties in automated clot detection – namely, cases where there is robust collateral flow, or residual flow and occlusions of the smaller vessels – and it is necessary to drive an initiative to overcome these challenges. Our dataset contains 159 multiphase CTA patient datasets, derived from CTP and annotated by expert stroke neurologists. In addition to images where the clot is marked, the expert neurologists have provided information about clot location, hemisphere and the degree of collateral flow. The data is available on request by researchers via an online form, and we will host a leaderboard where the results of clot detection algorithms on the dataset will be displayed. Participants are invited to submit an algorithm to us for evaluation using the evaluation tool, which is made available at together with the form at https://github.com/MBC-Neuroimaging/ClotDetectEval.

Abstract P340: Chronic Cerebrovascular Damage and Acute Embolic Mechanisms Associated With Acute Leptomeningeal Collateral Flow in Embolic Large Vessel Occlusion

Background and Purpose: Acute leptomeningeal collateral flow is vital to maintain blood perfusion to penumbral tissue in acute ischemic stroke due to large vessel occlusion (LVO). However, the degree of this collateral flow differs among patients. Patient premorbid factors as well as factors caused by the mechanisms of stroke are expected to be associated with this collateral flow. We aimed to investigate the clinical determinants of acute leptomeningeal collateral flow in embolic LVO. Methods: Among consecutive stroke patients caused by acute embolic anterior circulation LVO, we retrospectively reviewed 108 patients who underwent evaluation of acute leptomeningeal collateral status (CS) on pretreatment CTA admitted from January 2015 to December 2019. Both premorbid information including cerebrovascular risk factors and leukoaraiosis evaluated by the total white matter (WM) Fazekas score on MRI, which was calculated as periventricular plus deep WM scores, and stroke related information including stroke subtypes, severity, time course, and occlusive thrombus characteristics were collected. Among thrombus characteristics, thrombus length was measured by tracing the filling defect of contrast on CTA. The clinical determinants of good leptomeningeal CS (> 50% collateral filling of the occluded territory) were analyzed. Results: CS was good in 67 patients (62%). On multivariate logistic regression analysis, cardioembolic stroke subtype was negatively related (OR, 0.170; 95% CI, 0.022-0.868), and mild leukoaraiosis (total WM Fazekas scores of 0-2) was positively related (OR, 9.57; 95% CI, 2.49-47.75) to good CS. On subgroup analysis limited to 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.913 per mm increase; 95% CI, 0.819-0.999) as well as mild leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good CS. Conclusions: Premorbid leukoaraiosis and cardioembolic etiology are determinants of acute leptomeningeal collateral flow in embolic LVO. In addition, thrombus length is also a determinant of collateral flow in cardioembolic LVO. These findings indicate that a combination of chronic cerebrovascular damage and acute embolic mechanisms could determine the degree of leptomeningeal collateral flow.

Leptomeningeal Collateral Flow Modifies Endovascular Treatment Efficacy on Large-Vessel Occlusion Strokes.

We aim to evaluate if good collateral flow (CF) modifies endovascular therapy (EVT) efficacy on large-vessel stroke. To do that, we used final degree of reperfusion and number of device-passes performed, factors previously associated with better functional outcome, as main outcome measures. Single-center retrospective study including consecutive stroke patients receiving EVT for anterior circulation large-vessel stroke. CF degree was assessed on CT angiography before EVT using a previously validated 4-grade score. Final degree of reperfusion, using modified Thrombolysis in Cerebral Ischemia (mTICI), and number of device-passes performed were prospectively collected. Multivariable analysis was performed to evaluate the influence of collateral flow degree on final degree of reperfusion and number of device-passes performed. Six hundred twenty-six patients were included in the study; 369 patients (59%) presented good collateral flow on CT angiography. Five hundred twenty-two patients (84%) achieved successful reperfusion (mTICI 2B-3) after EVT, 304 (48%) of them with a final mTICI 2C-3. Median number of device-passes was 2 (interquartile range, 1-3). Good CF was independently associated with better final degree of reperfusion (shift analysis for mTICI0-2A/2B/2C-3%, poor CF 19/38/43 versus good CF 15/32/53, adjusted odds ratio, 1.51 [95% CI, 1.08-2.11]). Poor CF was independently associated with higher number of device-passes performed to achieve successful reperfusion (mTICI2B-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.59, [95% CI, 1.09-2.31]) and complete reperfusion (mTICI2C-3; shift analysis for 1/2/3/4+ device-passes, adjusted odds ratio, 1.70 [95% CI, 1.04-2.90]). Patients with good CF treated with EVT experience higher rates of successful reperfusion with lower number of device-passes. CF may facilitate thrombus retrieval and prevent distal embolization of clot fragments, improving device-passes efficacy.

Abstract WP291: Stochastic Methods Can Resolve the Dilemma of Emergency Stroke Transport

Introduction: Drip and Ship (DNS) and Mothership (MS) are well-known emergency transport strategies in acute stroke care, but the criteria for choosing between the two is widely debated. Existing models define time-dependent outcomes but cannot resolve this debate with statistical significance because the independent variables are deterministic. We propose a novel stochastic framework that quantifies statistical significance between DNS and MS in a network of primary and comprehensive stroke centers. Methods: We represented the physiology of ischemic core growth as a stochastic first-order differential equation, enabling infarct volume at time of reperfusion to be calculated and mapped to 90-day mRS. Using Texas as a case study, we configured the state’s stroke network within 15,811 geographic blocks as defined by census data. For each block, we ran Monte Carlo simulations to generate Beta distributions of large- and small-vessel infarct volumes, which were then translated into cumulative distribution functions of mRS. A two-sample Kolmogorov-Smirnov test for significance, and Cohen’s d effect size statistic for practical significance were computed between each DNS and MS pair. Stable effect sizes were assured by sampling > 5,000 total infarct volumes for each block. All model parameters were established from large cohort studies or trials. Results: Of the 13,113 blocks where the primary stroke center is the closest hospital from origin, DNS produces significantly better stroke outcomes than MS in 79.0% (0.3% SEM; P < 0.05; 0.2 < d < 0.5). For the subset of patients with large-vessel strokes, MS produces significantly better outcomes in 44.6% of blocks (1.3% SEM; P < 0.05; 0.4 < d < 0.85). Conclusion: Stochastic methods enable the use of clinically relevant metrics for comparative significance of DNS and MS in a geographic region. This formalism, which has not been incorporated in previous models, can be further generalized beyond stochastic infarct volumes if sufficiently large datasets become available. For example, the kinetic growth model can integrate the statistical distributions of times (pre-hospital and hospital) leading up to intervention, and patient attributes that affect outcomes, such as the degree of collateral flow and comorbidities.

Predictors for the extent of pial collateral recruitment in acute ischemic stroke.

Pial arterioles can provide a variable degree of collateral flow to ischemic vascular territories during acute ischemic stroke. This study sought to identify predictive factors of the degree of pial collateral recruitment in acute ischemic stroke. Clinical information and arteriograms from 62 consecutive patients with stroke due to either middle cerebral artery (MCA) M1 segment or internal carotid artery (ICA) terminus occlusion within 6 h following symptom onset were retrospectively reviewed. Pial collaterals were defined based on the extent of reconstitution of the MCA territory. Patients with slow antegrade flow distal to the occlusion site were excluded and no anesthetics were used prior or during angiography. Results were analyzed using multivariate nominal logistic regression. Better pial collateral recruitment was associated with proximal MCA versus ICA terminus occlusion (p = 0.005; odds ratio (OR) = 9.3; 95% confidence interval (CI), 2.16-53.3), lower presenting National Institutes of Health Stroke Scale Score (NIHSSS) (p = 0.023; OR = 6.51; 95% CI, 1.49-41.7), and lower diastolic blood pressure (p = 0.0411; OR = 5.05; 95% CI, 1.20-29.2). Age, gender, symptom duration, diabetes, laterality, systolic blood pressure, glucose level, hematocrit, platelet level, and white blood cell count at presentation were not found to have a statistically significant association with pial collateral recruitment. Extent of pial collateral recruitment is strongly associated with the occlusion site (MCA M1 segment versus ICA terminus) and less strongly associated with presenting NIHSSS and diastolic blood pressure.

Collateral Automation for Triage in Stroke: Evaluating Automated Scoring of Collaterals in Acute Stroke on Computed Tomography Scans

Computed tomography angiography (CTA) collateral scoring can identify patients most likely to benefit from mechanical thrombectomy and those more likely to have good outcomes and ranges from 0 (no collaterals) to 3 (complete collaterals). In this study, we used a machine learning approach to categorise the degree of collateral flow in 98 patients who were eligible for mechanical thrombectomy and generate an e-CTA collateral score (CTA-CS) for each patient (e-STROKE SUITE, Brainomix Ltd., Oxford, UK). Three experienced neuroradiologists (NRs) independently estimated the CTA-CS, first without and then with knowledge of the e-CTA output, before finally agreeing on a consensus score. Addition of the e-CTA improved the intraclass correlation coefficient (ICC) between NRs from 0.58 (0.46–0.67) to 0.77 (0.66–0.85, p = 0.003). Automated e-CTA, without NR input, agreed with the consensus score in 90% of scans with the remaining 10% within 1 point of the consensus (ICC 0.93, 0.90–0.95). Sensitivity and specificity for identifying favourable collateral flow (collateral score 2–3) were 0.99 (0.93–1.00) and 0.94 (0.70–1.00), respectively. e-CTA correlated with the Alberta Stroke Programme Early CT Score (Spearman correlation 0.46, p < 0.001) highlighting the value of good collateral flow in maintaining tissue viability prior to reperfusion. In conclusion, ­e-CTA provides a real-time and fully automated approach to collateral scoring with the potential to improve consistency of image interpretation and to independently quantify collateral scores even without expert rater input.

Total mismatch of diffusion-weighted imaging and susceptibility-weighted imaging in patients with acute cerebral ischemia

Background and purposeMultiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) is associated with an increased oxygen demand in acute cerebral ischemia. Occasionally, some patients exhibit extensive MHV on SWI despite of negative diffusion-weighted imaging (DWI), which is a phenomenon called total mismatch DWI-SWI. We analyzed the clinical characteristics and imaging findings in patients with the total DWI-SWI mismatch. Materials and methodsWe selected patients with total DWI-SWI mismatch who underwent MRI within 12hours from onset. To evaluate the degree of collateral flow, we graded vessels on post-contrast time-of-flight MR angiography as 3 groups. Perfusion lesion volume was measured using threshold of>6seconds of mean transit time on perfusion-weighted imaging. ResultsTotal DWI-SWI mismatch was found in 10 (2.7%) out of 370 patients. Four out of 10 patients were excluded due to lack of data on perfusion studies. Hence 6 patients were finally selected in the study. Two patients with internal carotid artery dissection were treated with emergent stenting, one patient with intravenous thrombolysis and mechanical thrombectomy, and two patients with drug-induced hypertension. All of the enrolled patients exhibited extensive MHV on SWI and good collateral flows. The mean perfusion lesion volume was 72.6±15.3ml (range 0–325.0ml). Clinical outcome was favorable in all of the patients (mRS at 3 months, 0). ConclusionsOur results demonstrate that total mismatch of DWI-SWI is associated with good collateral flow and may be a predictor of good response to treatment in patients with acute cerebral ischemia.

Combined analysis of myocardial function, viability, and stress perfusion in patients with chronic total occlusion in relation to collateral flow.

Indications for revascularisation in chronic total occlusion (CTO) of the coronary artery depend on the interplay between myocardial function, viability, and ischaemia. The technical feasibility of the procedure often relies on the collateral flow to the occluded artery. To assess the relation between the degree of collateral flow and characteristics of the myocardium supplied by the oc-cluded artery. The study included 54 patients (mean age 62 years, 85% males) with CTO referred for cardiovascular magnetic resonance (CMR) to assess indications for revascularisation. The presence of well-developed collateral flow was defined as a collateral connection grade = 2 and Rentrop score = 3. The presence of well-developed collaterals (n = 24, 44%) was less likely to be related to systolic dysfunction of the segments supplied by the occluded artery (mean wall motion score index 1.31 ± 0.44 vs. 1.64 ± 0.67, p = 0.04) in comparison to a lack of well-developed collaterals. Patients with well-developed collaterals had a lower frequency of previous myocar-dial infarction of the CTO territory (38% vs. 67%, p = 0.03) with similar frequency of transmural infarctions (21% vs. 23%, p = 0.83). They less frequently presented perfusion deficits of the CTO area during hyperaemia (42% vs. 70%, p = 0.03) and the size of deficits was smaller (median 0.0% [interquartile range 0-12%] vs. 7.5% [0-15%], p = 0.04). Myocardial segments supplied by CTO with well-developed collaterals are less prone to inducible ischaemia, have better systolic function, and are less likely to undergo myocardial infarction, in comparison to those supplied by CTO with poor collateral circulation. CMR is a non-invasive method that can be used for a comprehensive workup of patients be-ing considered for CTO revascularisation.

Avoid overtreatment in the setting of chronic total occlusions: The role of blood flow restoration in positive vascular remodeling

A coronary chronic total occlusion (CTO) promotes negative remodeling in distal segments by negative vascular wall remodeling and plaque growth [ [1] Park J.J. Chae I.H. Cho Y.S. et al. The recanalization of chronic total occlusion leads to lumen area increase in distal reference segments in selected patients: an intravascular ultrasound study. JACC Cardiovasc. Interv. Aug 2012; 5: 827-836 Crossref PubMed Scopus (31) Google Scholar ]. As a result, epicardial coronary segments located distal to a CTO appear often as diffusely diseased arteries [ [2] Werner G.S. Schwarz G. Prochnau D. et al. Paclitaxel-eluting stents for the treatment of chronic total coronary occlusions: a strategy of extensive lesion coverage with drug-eluting stents. Catheter. Cardiovasc. Interv. 2006; 67: 1-9 Crossref PubMed Scopus (46) Google Scholar ]. It is unknown if these lesions are related to clinical events at follow-up and if they require percutaneous coronary intervention (PCI) with stenting, because blood flow restoration by recanalisation potentially leads to positive vascular remodeling in the distal reference segments [ [3] Gasparini G.L. Rossi M.L. Presbitero P. Follow-up improvement of distal vessel diameter after successful chronic total coronary occlusion recanalization. JACC Cardiovasc. Interv. Apr 2014; 7: e31-e33 Crossref PubMed Scopus (4) Google Scholar ]. Few data have been published to investigate the role of blood flow restoration in remodeling process after successful CTO PCI. A study of Park et al. [ [1] Park J.J. Chae I.H. Cho Y.S. et al. The recanalization of chronic total occlusion leads to lumen area increase in distal reference segments in selected patients: an intravascular ultrasound study. JACC Cardiovasc. Interv. Aug 2012; 5: 827-836 Crossref PubMed Scopus (31) Google Scholar ] showed that recanalization of a CTO led to lumen area increase in two-thirds of the patients. Independent predictors of lumen area increase were occlusion duration, a poor collateral flow and statin use. The degree of collateral flow might reflect the magnitude of hemodynamic stimuli deprivation, whereas the CTO duration correlates with the time in which vessels undergo a negative remodeling process. In a study of Galassi et al. [ [4] Galassi A.R. Tomasello S.D. Crea F. et al. Transient impairment of vasomotion function after successful chronic total occlusion recanalization. J. Am. Coll. Cardiol. Feb 21 2012; 59: 711-718 Crossref PubMed Scopus (70) Google Scholar ] authors have suggested that improvement of distal vessel diameter after CTO recanalization can be explained by an impaired endothelium-dependent and/or -independent vasomotion immediately after CTO recanalization, that improves at follow-up, or by a positive remodeling or by a combination of both. Gomez-Lara et al. [ [5] Gomez-Lara J. Teruel L. Homs S. et al. Lumen enlargement of the coronary segments located distal to chronic total occlusions successfully treated with drug-eluting stents at follow-up. EuroIntervention. Feb 2014; 9: 1181-1188 Crossref PubMed Scopus (32) Google Scholar ] have documented a notable late lumen enlargement between baseline and follow-up. These findings can be explained either by the absence of vasomotor response to non-endothelium-mediated stimuli immediately after the procedure and plaque regression. At follow-up, endothelium-independent response was restored in most patients, showing a remarkable luminal gain compared to the index procedure.

Influence of leptomeningeal collateral pattern on the prognostic value of mismatch in acute anterior circulation stroke.

This study aimed to investigate whether and to what degree leptomeningeal collateral flow as detected on angiography influences the prognostic value of computed tomography perfusion-estimated mismatch in interventional treatment of acute anterior circulation stroke. Thirty-eight consecutive patients with acute anterior circulation stroke who received interventional neuroradiologic treatment were assigned one of 2 groups depending on the patient's degree of collateral flow (18 patients with poor collaterals, 20 patients with high degree collaterals) according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system. In a multiregression model, we investigated a possible interaction between 2 independent variables mismatch ratio and degree of collateral flow using a "centered" variable approach. The mismatch ratio per se showed a significant correlation with final clinical outcome (β coefficient, -0.79; P = 0.02); whereas, there was no interaction shown between mismatch degree of collateral flow (β coefficient, 0.54; P = 0.1). This study suggests that the predictive value of computed tomography perfusion-estimated mismatch is not influenced by the degree of leptomeningeal collateral flow.

Multiple Hypointense Vessels on Susceptibility-Weighted Imaging in Acute Ischemic Stroke: Surrogate Marker of Oxygen Extraction Fraction in Penumbra?

Background: Multiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) are frequently observed in patients with acute cerebral ischemia, but their implication has not been clearly established. To elucidate the clinical significance of MHV on SWI, we investigated the association of MHV on SWI with clinical data and other MR markers in patients with acute ischemic stroke. Methods: We enrolled acute stroke patients with internal carotid or proximal middle cerebral artery occlusion who underwent MRI including SWI within 3 days from stroke onset. Baseline clinical data were reviewed. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). We graded the degree of MHV on SWI as four groups of none, subtle, relative, or extensive by the modified Alberta Stroke Program Early CT Scan (ASPECTS) system. To evaluate the degree of collateral flow, distal hyperintense vessels (DHV) on FLAIR and vessels on post-contrast time-of-flight MR angiography (TOF MRA) source images were graded respectively as 3 groups: none/subtle/prominent and poor/moderate/good. Diffusion and perfusion lesion volume and diffusion-perfusion mismatch (DPM) ratio were measured in all patients. We analyzed the association of the degree of MHV on SWI with clinical data and MR markers. Results: Eighty patients were included in the study. The mean MR time from stroke onset was 12.4 h (range 0.5-63.0). There is no difference in MR time from stroke onset between groups of MHV on SWI. MHV were observed in 68 (85%) of 80 patients: none in 12, subtle in 11, relative in 13, and extensive in 44. There were no statistically significant associations between MHV on SWI and vascular risk factors. Patients with more extensive MHV on SWI had a smaller diffusion volume (p < 0.001), larger DPM (p < 0.001), and lower initial NIHSS scores (p = 0.022). Prominent DHV was presented in 29 of 44 patients with extensive MHV (p < 0.001). Good collateral flow on TOF MRA source images was presented in 37 of 44 patients with extensive MHV (p < 0.001). Conclusions: More extensive MHV on SWI in acute ischemic stroke is associated with lower initial NIHSS scores, smaller diffusion lesion volume, better collateral flow, and larger DPM. Our results show the possibility that MHV on SWI may be a useful surrogate marker for predicting increased oxygen extraction fraction and diffusion-perfusion mismatch in acute ischemic hemisphere.

The combination of baseline magnetic resonance perfusion-weighted imaging-derived tissue volume with severely prolonged arterial-tissue delay and diffusion-weighted imaging lesion volume is predictive of MCA-M1 recanalization in patients treated with endovascular thrombectomy

IntroductionIndices of collateral flow deficit derived from MR perfusion imaging that are predictive of MCA-M1 recanalization after intravenous thrombolysis have been recently reported. Our objective was to test the performance of such MRI-derived collateral flow indices for prediction of recanalization after endovascular thrombectomy.MethodsFifty-seven patients with MCA-M1 occlusion evaluated with multimodal MRI prior to thrombectomy were included. Bayesian processing allowed quantification of collateral perfusion indices like the volume of tissue with severely prolonged arterial-tissue delay (>6 s) (VolATD6). Baseline DWI lesion volume was also measured. Correlations with angiographic collateral flow grading and post-thrombectomy recanalization were assessed.ResultsVolATD6 < 27 ml or DWI lesion volume <15 ml provide the most accurate diagnosis of excellent collateral supply (p < 0.0001). The combination of VolATD6 > 27 ml and DWI lesion volume >15 ml significantly discriminates recanalizers versus nonrecanalizers (whole cohort, p = 0.032; MERCI cohort (n = 50), p = 0.024). When both criteria are positive, 76.2 % of the patients treated with the MERCI retriever do not fully recanalize (p = 0.024). In multivariate analysis, the aforementioned combined criterion and the angiographic collateral grade are the only independent predictors of recanalization with the MERCI retriever (p = 0.015 and 0.029, respectively).ConclusionBayesian arterial-tissue delay maps and DWI maps provide a non-invasive assessment of the degree of collateral flow and a combined index that is predictive of MCA-M1 recanalization after endovascular thrombectomy. Further studies are needed to evaluate the accuracy of this index in patients treated with novel stent retriever devices.

Abstract WP20: Procedure Time and Degree of Collateral Flow Determines Outcome in Acute Endovascular Stroke Therapy

BACKGROUND AND PURPOSE: Treatment options for acute ischemic stroke remain limited. There is a clear time dependant nature to this condition, though more evidence is accumulating that degree of collateral flow is a powerful modulator of the effect of time in acute ischemic stroke. In addition, longer procedural times have been associated with worse outcome. We sought to study the relationship between procedure times, collateral flow, recanalization, and clinical outcomes. MATERIALS AND METHODS: A retrospective review of prospectively collected database of 152 patients with anterior circulation strokes treated with endovascular stroke therapy within 8 hours of symptom onset from August 2006 to December 2011. General demographics, clinical features, imaging findings, and outcomes were collected. Univariate and multivariate analysis was performed using JMP statistical analysis software. RESULTS: 152 patients [71 (46.7%) male, mean age: 68±15 years;] were included in the analysis. Complete or partial revascularization occurred in 121 (81%) patients. Collateral circulation was assessed on CTA with 7 (0.6%) having no significant collateral flow, 22 (20.7%) having low collateral flow (50% of affected territory), and 28 (26.4%) having full collateral flow. Overall, there was no significant difference in the baseline clinical and radiographic features between the groups. Analysis of procedural times showed significantly reduced chance of good outcome with procedure times &gt;90 minutes. This effect was more pronounced based on collaterals; in those with good collaterals, good outcome (mRS ≤3) was significantly higher in procedures &lt; 90 minutes (56% vs. 24%; p=0.02); in those with poor collaterals, no good outcomes were seen after 90 minutes of procedure time (39% vs. 0%; p=0.02). CONCLUSION: Procedure time and the degree of collateralization play a significant role in determining outcome in patients who undergo endovascular therapy in acute ischemic stroke, with significantly worse outcomes seen in patients with procedure times &gt;90 minutes, particularly in those with poor collaterals. Treating physicians should keep these factors in mind during the treatment of acute stroke patients.

Observed influence of nitroglycerine on myocardial perfusion scintigraphy in patients with multiple vessel coronary artery disease and well-developed collaterals

Observed influence of nitroglycerine on myocardial perfusion scintigraphy in patients with multiple vessel coronary artery disease and well-developed collaterals

Pharmacological possibilities for protection against myocardial reperfusion injury.

Reperfusion through thrombolysis or percutananeous coronary angioplasty is standard treatment in impending acute myocardial infarction. Although restoration of blood flow to the jeopardised myocardial area is a perquisite for myocardial salvage, reperfusion itself may lead to accelerated and additional myocardial injury beyond that generated by ischemia alone. This is referred to as the "reperfusion injury". Since the reperfusion injury is initiated by the treatment of myocardial infarction, it is of importance to limit the extent of the injury. Several studies aimed at preventing reperfusion injury by means of pharmacological agents have therefore been conducted. The design of such studies is crucial for the results. Factors of importance are the timing of drug administration, animal species used, the degree of collateral flow and the duration of ischemia. A variety of pharmacological compounds have been investigated in different experimental models of myocardial ischemia and reperfusion. These include oxygen free radical scavengers, antioxidants, calcium channel blockers, inhibitors of neutrophils, nitric oxide, adenosine-related agents, inhibitors of the renin-angiotensin system, endothelin receptor antagonists, Na(+)/H(+) exchange inhibitors, and anti-apoptotic agents. All these groups of pharmacological agents have been demonstrated to protect from reperfusion injury determined as limitation of infarct size, improved myocardial and endothelial function, and reduced incidence of arrhythmias. The mechanism behind the protective effect may differ between different groups of compounds, but some compounds may exert cardioprotection via common pathways. Such a pathway may be via maintained bioavailability of nitric oxide.

Early infarct artery collateral flow does not improve long-term survival following thrombolytic therapy for acute myocardial infarction

It is known that acutely developed collaterals can prevent the onset of acute myocardial infarction (AMI) in the presence of a total coronary occlusion. However, there still is controversy concerning long-term follow-up of coronary collateral circulation to the infarct-related artery. In this study we analyze the prognostic role of collateral flow (degrees 0 to 3) as well as anterograde flow (degrees 0 to 3) in patients with AMI treated with thrombolytic therapy. Four hundred twenty-two patients (median age 57 years, 355 men) with AMI were treated with intravenous streptokinase and followed prospectively for up to 8 years. At the end of the study period, patients with collateral coronary flow 3 (n = 30) and those with flow <3 (n = 392) at in-hospital coronary arteriography had survival rates of 66% and 85%, respectively (p <0.12). Meanwhile, patients with coronary anterograde flow 3 (n = 189) and those with flow <3 (n = 233) had survival rates of 89% and 80%, respectively (p <0.04). By censored regression analysis, a negative correlation was found between coronary collateral flow degree and survival (p = 0.0498) and, inversely, a positive correlation was found between coronary anterograde flow degree and survival (p = 0.0053). By Cox multivariate analysis, the following variables showed significant correlations with long-term survival: global left ventricular ejection fraction (p = 0.0003), anterograde flow degree (p = 0.0006), collateral flow degree (negative correlation, p = 0.0179), and medical treatment (negative correlation, p = 0.0464). Thus, patients treated with intravenous streptokinase during AMI and with adequate coronary collateral circulation had a worse prognosis than those who developed adequate anterograde flow, probably because of residual myocardial ischemia. Such patients may benefit from coronary revascularization (angioplasty or surgery) to restore anterograde blood flow and minimize myocardium at risk.

Long-term physical exercise and quantitatively assessed human coronary collateral circulation

Objectives. This prospective, cross-sectional study sought to determine an association between the level of long-term physical activity as well as other clinical and angiographic variables and an index of collateral flow to the vascular region undergoing percutaneous transluminal coronary angioplasty (PTCA).Background. There is limited and conflicting information about the effect of physical exercise on the coronary collateral circulation in humans, partly because previous studies lacked a quantitative means of assessing collateral channels.Methods. In 79 patients (mean [±SD] age 58 ± 10 years) with coronary artery disease undergoing PTCA (no transmural myocardial infarction), a coronary collateral flow index was determined as the ratio between the intracoronary (IC) distal flow velocity time integral during (Vioccl[cm]) and after (Viø-occl[cm]) PTCA of the stenosis. Vioccl/Viø-occlwas measured by a 0.014-in. Doppler guide wire, from which an IC electrocardiogram (ECG) was also recorded. Patients without ECG ST-T wave changes during PTCA were considered to have sufficient collateral channels (n = 29); those with ST-T wave changes were considered to have insufficient collateral channels (n = 50). The level of long-term physical activity was determined by a structured interview (score from 1 to 4). Univariate and multivariate analyses were used to find associations between physical activity as well as 30 other clinical and angiographic variables and the collateral flow index.Results. Long-term physical activity during leisure time, but not during work hours, and the severity of the stenosis undergoing PTCA were found to be independently and directly associated with sufficient versus insufficient collateral channels and with Vioccl/Viø-occl(leisure time physical activity [LTPA] score 3.3 ± 0.9 vs. 2.4 ± 1.0, p = 0.0002; percent diameter stenosis 88 ± 12% vs. 80 ± 14%, p = 0.001; Vioccl/Viø-occl= 0.1+0.1 LTPA score, p = 0.0002 for trend).Conclusions. In patients with coronary artery disease, the level of long-term physical activity during leisure time and the severity of the stenosis undergoing PTCA are directly associated with the quantitative degree of collateral flow.

The role of antegrade and collateral flow in relation to left ventricular function post-thrombolysis

The aim of the study was to analyze the relationship between antegrade and collateral flow degree to the “culprit” coronary artery, and between both variables and left ventricular systolic function. We analyzed five hundred patients with acute myocardial infarction, treated prospectively and consecutively within 6 h of evolution with intravenous streptokinase. The degree of antegrade (0–3) and collateral blood flow (0–3) were correlated with 18 other variables. Results: (a) By simple regression analysis, antegrade flow degree correlated positively (p<0.0001), and collateral flow degree negatively (p=0.0073) with left ventricular ejection fraction; (b) By multiple regression analysis, antegrade flow degree (p=0.0032), but not collateral flow degree (p>0.1), correlated independently with left ventricular ejection fraction; (c) In the subgroup of patients with occluded “culprit” coronary artery, the mean ejection fraction was significantly higher for those with collateral flow 3 (60.2%±13.3) in relation to those with collateral flow <3 (53.9%±13.1, p=0.032, 95% CI 11.96 to 0.53%). In conclusion, antegrade coronary flow degree, but not collateral flow degree, correlated significantly and independently with left ventricular ejection fraction. However, in the subgroup of patients with occluded “culprit” coronary artery, collateral flow 3 led to better left ventricular systolic function, in relation to collateral flow <3.

Pathophysiology of Brain Ischemia as It Relates to the Therapy of Acute Ischemic Stroke

Current knowledge of the pathophysiology of cerebral ischemia, summarized in the present study, predicts that neurological deficits caused by moderate ischemia (flows in the penumbral range between 23 and 10 ml/100 g/min) are reversible provided flow is restored within 3-4 h of onset. It also predicts that areas of dense ischemia cannot be salvaged and that reperfusion of such areas is risky, because massive edema or even hemorrhage may develop following reperfusion. On this basis, it is argued that selection of stroke cases for thrombolysis or surgical revascularization must be based not only on computed tomographic (CT) scanning to exclude hemorrhagic stroke, but also on cerebral blood flow (CBF) tomography to exclude lacunar infarcts, early reperfusion, and dense ischemia. The methods available for routing CBF tomography in acute stroke cases are discussed, and it is concluded that single photon emission computed tomography (SPECT) using [99mTc]hexamethyl propyleneamine oxide (HM-PAO) or [99mTc]ethyl cysteinate dimer (ECD) should be explored for this use. In concluding, the glutamate receptor antagonist is mentioned. This compound is therapeutically active in some animal stroke models. In humans, it is probably used only in the acute phase, and in those in whom some degree of collateral flow is preserved. Therefore, even with this therapeutic approach, CBF tomography may be of value for patient selection.