Collateral Circulation

BackgroundAcute ischemic stroke (AIS) is a common neurological event that causes varying degrees of disability. AIS outcome varies considerably, from complete recovery to complete loss of tissue and function. This diversity is partly explained by the compensatory ability of the collateral circulation and the ensuing cerebral flow grade. The collateral flow to the anterior circulation largely supplies the cortical areas. The deep brain tissue is supplied by penetrating arteries and has little or no collateral supply. Although these brain compartments differ substantially in their collateral supply, there are no published data on the different effects the collateral circulation has on them. In addition, the influence of baseline collateral flow on the final infarct size following endovascular or reperfusion therapies remains unknown. This study was designed to determine the effect of the collateral circulation on cortical infarct volume and deep infarct volume, and to investigate the relation between the collateral grade, response to reperfusion therapy and clinical outcome.MethodsWe studied consecutive patients presenting to our medical center between April 2008 and April 2012 with AIS and anterior proximal artery occlusion. To be included patients had to undergo a computerized tomographic angiographic study within 12 h of symptom onset demonstrating the occlusion. Imaging data and clinical and laboratory values were extracted retrospectively from the original scans and medical records. Cortical infarct volume (CIV) and deep infarct volume (DIV) were calculated as well as collateral grade. Clinical outcome was assessed at discharge using the modified Rankin Scale (mRS).ResultsOf the 51 study patients, 13 were treated conservatively, 22 received intravenous recombinant tissue plasminogen activator, and 16 received intra-arterial thrombolysis. The collateral grading was similar for all three treatment groups. While there was a moderate inverse correlation between the collateral grade and CIV (Spearman's rho = -0.49, P ConclusionsOur data shows that the collateral circulation is an important determinant of cortical infarct volume and, in turn, of clinical outcome in the setting of anterior circulation major artery occlusion. Our findings further demonstrate the benefit of recanalization in sparing cortical tissue from injury. Additional studies are needed to determine the impact of stroke therapy on the final infarct volume in relation to the collateral grade.

Collaterals are unique blood vessels present in the microcirculation of most tissues that, by cross-connecting a small fraction of the outer branches of adjacent arterial trees, provide alternate routes of perfusion. However, collaterals are especially susceptible to rarefaction caused by aging, other vascular risk factors, and mouse models of Alzheimer's disease-a vulnerability attributed to the disturbed hemodynamic environment in the watershed regions where they reside. We examined the hypothesis that endothelial and smooth muscle cells (ECs and SMCs, respectively) of collaterals have specializations, distinct from those of similarly-sized nearby distal-most arterioles (DMAs) that maintain collateral integrity despite their continuous exposure to low and oscillatory/disturbed shear stress, high wall stress, and low blood oxygen. Examination of mouse brain revealed the following: Unlike the pro-inflammatory cobble-stoned morphology of ECs exposed to low/oscillatory shear stress elsewhere in the vasculature, collateral ECs are aligned with the vessel axis. Primary cilia, which sense shear stress, are present, unexpectedly, on ECs of collaterals and DMAs but are less abundant on collaterals. Unlike DMAs, collaterals are continuously invested with SMCs, have increased expression of Pycard, Ki67, Pdgfb, Angpt2, Dll4, Ephrinb2, and eNOS, and maintain expression of Klf2/4. Collaterals lack tortuosity when first formed during development, but tortuosity becomes evident within days after birth, progresses through middle age, and then declines-results consistent with the concept that collateral wall cells have a higher turnover rate than DMAs that favors proliferative senescence and collateral rarefaction. In conclusion, endothelial and SMCs of collaterals have morphologic and functional differences from those of nearby similarly sized arterioles. Future studies are required to determine if they represent specializations that counterbalance the disturbed hemodynamic, pro-inflammatory, and pro-proliferative environment in which collaterals reside and thus mitigate their risk factor-induced rarefaction.

BackgroundRecent studies have substantiated the role of the triglyceride glucose (TyG) index in predicting the prognosis of coronary artery disease (CAD) patients, while no relevant studies have revealed the association between the TyG index and coronary collateralization in the event of coronary chronic total occlusion (CTO). The current study intends to explore whether, or to what extent, the TyG index is associated with impaired collateralization in CAD patients with CTO lesions.MethodsThe study enrolled 1093 CAD patients undergoing cardiac catheterization for at least one CTO lesion. Data were collected from the Beijing Anzhen Hospital record system. The degree of collaterals was determined according to the Rentrop classification system. The correlation between the TyG index and coronary collateralization was assessed.ResultsOverall, 318 patients were included in a less developed collateralization (Rentrop classification 0-1) group. The TyG index was significantly higher in patients with impaired collateralization (9.3±0.65 vs. 8.8±0.53, PConclusionsThe increased TyG index is strongly associated with less developed collateralization in CAD patients with CTO lesions and its risk assessment performance is better than single metabolic abnormality indicators.

Leptomeningeal collateral vessels help redistribute cerebral blood flow following arterial obstruction, reducing tissue damage. This study investigates the Tie2 receptor peptide agonist Vasculotide in a permanent middle cerebral artery occlusion (pMCAO) model. Vasculotide enhanced early diameter enlargement of pre-existing pial collaterals, which may be mediated by structural remodeling, as evidenced by endothelial proliferation. These changes correlated with reduced infarct volume, blood-brain barrier disruption, enhanced blood flow, and functional recovery at 3-28 days post-pMCAO. Conditional endothelial cell (EC)-specific EphA4 knockout (KO) mice exhibited increased Tie2 and Ang-1 expression, mimicking the effects of Vasculotide on collateral size. Simultaneous genetic loss of EC-specific EphA4 and Tie2 attenuated these outcomes. Nitric oxide inhibition partially blocked collateral enlargement in EC-KO mice, suggesting the presence of additional contributors. Bulk RNAseq of meningeal tissue revealed upregulation of Krt5, Krt14, and Col17a1 in the ipsilateral meninges of Vasculotide-treated and EC-specific EphA4 KO mice. Notably, the number of Krt5-expressing cells is increased on the leptomeningeal arterial vasculature of KO mice, suggesting a novel contribution to collateral enlargement. The opposing roles of EphA4 and Tie2 in collateral dynamics are demonstrated, and a novel molecular program is identified that can be targeted to enhance their diameter enlargement in ischemic stroke.