Development Of Collateral Arteries Research Articles

Regression of periventricular anastomosis after indirect revascularization in pediatric patients with moyamoya disease.

The aim of this study was to evaluate whether indirect revascularization in pediatric patients with moyamoya disease leads to periventricular anastomosis (PVA) regression, which is markedly developed in moyamoya vessels and is regarded as a risk factor for hemorrhage. Pediatric patients with moyamoya disease treated with indirect revascularization from 2011 to 2021 were included in this study. Magnetic resonance angiography and arterial spin labeling images acquired before and 1 year after surgery were assessed to obtain a visual scale of postoperative collateral artery formation, moyamoya vessels, PVA, and quantitative values of cerebral blood flow (CBF). The relationship between background information (age, sex, RNF213 p.R4810K variant status, and preoperative CBF) and postoperative collateral artery formation, as well as postoperative CBF improvement and regression of moyamoya vessels and PVA, was evaluated. Of 89 hemispheres in 58 patients (34 females; mean [SD] patient age 8.0 [3.4] years), 74.2% showed good postoperative collateral artery formation and a significant increase in CBF (p < 0.001). Postoperative PVA showed significant regression (postoperative score 1.46 [1.06] vs 2.02 [1.69], p = 0.001), especially in those arising from choroidal arteries (postoperative score 0.28 [0.50] vs 0.72 [0.67], p < 0.001). Compared with hemispheres without good collateral artery formation, those with good collateral artery formation were more likely to show a higher increase in CBF (9.74 [12.44] ml/min/100 g vs -4.86 [9.68] ml/min/100 g, p < 0.001) and regression of PVA (54.5% [36/66] vs 30.4% [7/23], p = 0.015). Although not statistically significant, patients with postoperative PVA progression were younger than those with regression (6.75 [3.03] years vs 8.18 [3.17] years, p = 0.188), and patients with the RNF213 p.R4810K variant were more likely to show regression (28/57 [49.1%] hemispheres vs 5/13 [38.5%] hemispheres, p = 0.069). Indirect revascularization in pediatric patients with moyamoya disease resulted in good collateral extracranial artery formation and an increase in CBF and PVA regression, especially of vessels arising from choroidal arteries. With good postoperative collateral artery development, patients were more likely to show improved CBF and regression of moyamoya vessels, including PVA. Whether postoperative PVA changes reduce future hemorrhage risk requires further investigation.

Stem Cell Therapy in Critical Limb Ischemia.

Critical limb ischemia (CLI), a serious outcome of peripheral artery disease, is frequently associated with morbid outcomes. The available treatment modalities do not provide satisfactory results, leading to marked morbidities such as joint contracture and amputations, resulting in a high economic burden. The peripheral vascular disease tends to cause more morbidity in patients with diabetes and atherosclerosis, given the pre-existing compromised perfusion of medium and small vessels in diabetic patients. With surgical procedures, the chance of vascular compromise further increases, inducing a significantly greater rate of amputation. Hence, the need for nonsurgical treatment modalities such as stem cell therapy (SCT), which promotes angiogenesis, is warranted. In CLI, SCT acts through neovascularization and the development of collateral arteries, which increases blood supply to the soft tissues of the ischemic limb, providing satisfactory outcomes. An electronic database search was performed in PubMed, SCOPUS, EMBASE, and ScienceDirect to identify published clinical trial data, research studies, and review articles on stem cell therapy in critical limb ischemia. The search resulted in a total of 2391 results. Duplicate articles screening resulted in 565 articles. In-depth screening of abstracts and research titles excluded 520 articles, yielding 45 articles suitable for full-text review. On review of full text, articles with overlapping and similar results were filtered, ending in 25 articles. SCT promotes arteriogenesis, and bone marrow-derived mesenchymal stromal cells produce significant effects like reduced morbidity, improved amputation-free survival (AFS ) rate, and improved distal perfusion even in "no-option" CLI patients. SCT is a promising treatment modality for CLI patients, even in those in whom endovascular and revascularization procedures are impossible. SCT assures a prolonged AFS rate, improved distal perfusion, improved walking distances, reduced amputation rates, and increased survival ratio, and is well-tolerated.

Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.

Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate. Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice. Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts. These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

Moyamoya Disease Complicating Ebstein's Anomaly.

Ebstein's anomaly is an uncommon congenital disorder affecting the tricuspid valve. We herein report a 38-year-old woman who experienced consciousness and sensory disturbance during treatment for heart failure caused by Ebstein's anomaly. Urgent magnetic resonance imaging and cerebral angiography demonstrated acute cerebral infarction and internal carotid artery obstruction with the development of collateral arteries. We diagnosed her with multiple cerebral infarctions due to moyamoya disease. Ebstein's anomaly concomitant with moyamoya disease is extremely rare. However, we should consider the possibility of this rare but important concurrence when treating patients with heart failure due to Ebstein's anomaly to avoid excessive diuresis and vasodilation and irreversible brain injury.

Impact of Anatomical Sub-types and Shunt Types on Aortopulmonary Collaterals in Hypoplastic Left Heart Syndrome

This study aims to clarify the relation of development of aortopulmonary collateral arteries (APCs) with anatomical sub-types and the shunt types at Norwood procedure in patients with hypoplastic left heart syndrome (HLHS). A total of 140 patients with HLHS who completed 3 staged palliation between 2003 and 2019 were included. Incidence of APCs and corresponding interventions were examined using angiogram by cardiac catheterization, with respect to the anatomical sub-types and shunt types. Totally, APCs were observed in 87 (62%) of the patients; pre-stage II in 32 (23%), pre-stage III in 64 (46%), and after stage III in 40 (29%). The incidence of APCs before stage II was significantly higher in patients with aortic atresia/mitral atresia (AA/MA) compared with other sub-types (P = 0.022). Patients with right ventricle to pulmonary artery conduit (RVPAC) had a higher incidence of APCs originating from the descending aorta, compared with those with modified Blalock-Taussig shunt (20% vs 2%, P= 0.002). Interventions for APCs were performed in 58 (41%) patients; before stage II in 10 (7%), after stage II in 7 (5%), before stage III in 22 (16%), and after stage III in 32 (23%). Patients with AA/MA had more interventions before stage II (P= 0.019), and patients with aortic stenosis/mitral stenosis (AS/MS) had a lower incidence of interventions after stage III (P= 0.047). More than half of the patients with HLHS developed APCs. Before stage II, patients with AA/MA sub-type had a higher incidence of APCs, and those with RVPAC had significantly more APCs from the descending aorta.

McKeown esophagectomy with concomitant median arcuate ligament release in a case of esophageal cancer with celiac artery stenosis

BackgroundThe celiac artery stenosis due to compression by median arcuate ligament (MAL) has been reported in many cases of pancreaticoduodenectomy, but not in cases of esophagectomy. Recently, the celiac artery stenosis due to MAL or arteriosclerosis has been reported to be associated with the gastric tube necrosis or anastomotic leakage following Ivor–Lewis esophagectomy. Herein, we present the first reported case of esophageal cancer with celiac artery stenosis due to compression by the MAL successfully treated by McKeown esophagectomy and gastric tube reconstruction following prophylactic MAL release.Case presentationA 72-year-old female patient was referred to our department for esophagectomy. The patient had received two courses of neoadjuvant chemotherapy with 5-FU and cisplatin for T2N0M0 squamous cell carcinoma of the middle esophagus. Preoperative contrast-enhanced computed tomography (CECT) showed celiac artery stenosis due to compression by the MAL. The development of collateral arteries around the pancreatic head was observed without evidence of aneurysm formation. The patient reported no abdominal symptoms. After robot-assisted esophagectomy with mediastinal lymphadenectomy, gastric mobilization, supra-pancreatic lymphadenectomy, and preparation of the gastric tube were performed under laparotomy. Subsequently, the MAL was cut, and released to expose the celiac artery. Improved celiac artery blood flow was confirmed by decreased pulsatility index on intraoperative Doppler sonography. The operation was completed with the cervical esophagogastric anastomosis following cervical lymphadenectomy. Postoperative CECT on postoperative day 7 demonstrated increased celiac artery patency. The patient had an uncomplicated postoperative course thereafter.ConclusionsProphylactic MAL release may be considered in patients with celiac artery stenosis due to compression by the MAL on preoperative CECT for esophagectomy.

Elastic Laminar Reorganization Occurs with Outward Diameter Expansion during Collateral Artery Growth and Requires Lysyl Oxidase for Stabilization.

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that deconstruction of the extracellular matrix is essential to remodel smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of internal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content was low. Outward remodeling of these vessels with a 10–20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension, as demonstrated by the straightening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

Risk factors for spinal cord ischemia in frozen elephant trunk\u2013induced upper spinal cord ischemia in patients with combination of degenerative arch aneurysms and peripheral artery diseases: a possible mechanism

BackgroundDegenerative aortic arch aneurysms are known to develop through a pathological process of arterial atherosclerosis, which could be accompanied by peripheral artery diseases and resultant development of intrapelvic collateral arteries to the ischemic lower limbs. The aim of this study was to investigate the relationship between peripheral collateral circulation and postoperative paraplegia after total arch repair with a frozen elephant trunk in patients with degenerative aortic arch aneurysms and peripheral artery diseases.MethodsBetween October 2014 and March 2020, 27 patients (20 men; 69.8 ± 7.7 years old) underwent total arch repair with a frozen elephant trunk. Two of the 27 patients developed paraplegia postoperatively. The patients were divided into two groups, spinal cord ischemia (SCI) group (2 patients) and no-SCI group (25 patients). The aortic shagginess score, arterial calcification (subclavian artery; hypogastric artery) score, and the number of hypogastric artery branches, assessed using preoperative contrast-enhanced computed tomography images, were compared between the two groups.ResultsThe ankle brachial artery pressure index (i.e., lower side value each patient) was lower in the SCI group than that in the no-SCI group (0.64, 0.71, and 1.09±0.07, respectively). There was no difference between the two groups in the arterial calcification scores or the aortic shagginess score. The number of hypogastric artery branches was greater in the SCI group than in the no-SCI group (66, 66, and 30.7±7.5, respectively).ConclusionsEnhanced collateral circulation to the ischemic lower limbs in patients with combination of degenerative aortic arch aneurysms and peripheral artery diseases may be involved in paraplegia the upper thoracic spinal cord injury after total arch repair with a frozen elephant trunk.

New Research Is Shining Light on How Collateral Arteries Form in the Heart: a Future Therapeutic Direction?

Collateral arteries create artery-artery anastomoses that could serve as natural bypasses that in the heart could relieve the various complications of ischemia heart disease. Recent work using animal models have begun to reveal details of how coronary collateral arteries form. Mouse genetics has been used to study the cellular and molecular mechanisms of collateral artery development. Collateral arteries are not pre-existing in the mouse heart, and only form in response to injury. Myocardial infarction creates tissue hypoxia that triggers the expression of growth factors and chemokines that guide collaterogenesis. Collateral development is more robust in neonatal hearts when compared with adults, and contributes to neonatal heart regeneration. The identification of signaling pathways and cellular responses underlying coronary collateral artery development suggests potential translational strategies. Continued investigation into this subject could lead to the identification of targetable pathways that induce collateral arteries for cardiac revascularization.

Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease.

Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.

Tumor suppressor protein p53 negatively regulates ischemia-induced angiogenesis and arteriogenesis

ObjectiveThe tumor suppressor protein p53 regulates angiogenesis and is a key regulatory mediator of cellular apoptosis, proliferation, and growth. p53 expression is induced in response to ischemia; however, its role in regulating ischemia-induced angiogenesis and arteriogenesis remains undefined. The objective of this study was to define the role of p53 in regulating ischemia-induced angiogenesis and arteriogenesis and to identify mechanisms by which this regulation occurs in vivo. MethodsSurgically induced hindlimb ischemia or mesenteric artery ligation was performed in wild-type (p53+/+) and p53 knockout (p53−/−) mice. Limb perfusion and revascularization were assessed by laser Doppler perfusion imaging, capillary density, and collateral artery development. Mesenteric collateral artery flow and development were determined by arterial flow measurement and by histologic analysis, respectively. An in vitro aortic ring assay was performed on p53+/+ and p53−/− aortic tissue to evaluate endothelial function. The p53 inhibitor and activator pifithrin-α and quinacrine, respectively, were used to modulate p53 activity in vivo after ischemia. ResultsAbsence of p53 in mice resulted in increased limb perfusion (P < .05), capillary density (P < .05), and collateral artery development (P < .05) after induction of hindlimb ischemia. In the nonischemic mesenteric artery ligation model of arteriogenesis, p53 expression was induced in collateral arteries and increased arterial blood flow in mice lacking p53 (P < .05). Lack of p53 decreased apoptosis in ischemic hindlimb tissue (P < .05) and increased proangiogenic factors hypoxia-inducible factor 1α and vascular endothelial growth factor (VEGF). Endothelial cell outgrowth in vitro increased in the absence of p53 (P < .05). Pharmacologic augmentation of p53 expression after ischemia impaired perfusion and collateral artery formation and decreased VEGF levels (P < .05). Conversely, inhibition of p53 with pifithrin-α augmented limb perfusion (P < .05) and collateral artery formation (P < .05) and increased protein levels of hypoxia-inducible factor 1α and VEGF. Pharmacologic augmentation and inhibition of p53 had no significant effect in mice lacking p53. Conclusionsp53 negatively regulates ischemia-induced angiogenesis and arteriogenesis. Inhibition of p53 increases ischemia-induced arteriogenesis and limb perfusion and thus represents a potential therapeutic strategy for arterial occlusive disease.

A modified rat model of hindlimb ischemia for augmentation and functional measurement of arteriogenesis.

Arteriogenesis (collateral artery development) is an adaptive pathway critical for salvage of tissue in the setting of arterial occlusion. Rodent models of arteriogenesis typically involve an experimental occlusion (ligation) of a hindlimb artery and then rely on indirect measures such as laser Doppler perfusion imaging to assess blood flow recovery. Unfortunately, the more commonly utilized measures of distal tissue perfusion at rest are unable to account for hemodynamic and vasoactive variables and thus provide an incomplete assessment of collateral network capacity. We provide a detailed description of modifications to the commonly used model of femoral artery ligation. These serve to alter and then directly assess collateral network’s hemodynamic capacity. By incorporating an arteriovenous fistula distal to the arterial ligation, arterial growth is maximized. Hindlimb perfusion may be isolated to measure minimum resistance of flow around the arterial occlusion, which provides a direct measure of collateral network capacity. Our results reinforce that arteriogenesis is driven by hemodynamic variables, and it can be reliably augmented and measured in absolute terms. Using these modifications to a widely used model, functional arteriogenesis may be more directly studied.

Evaluation of Collateral Source Characteristics With 3-Dimensional Analysis Using Micro-X-Ray Computed Tomography.

BackgroundCollateral arteries provide an alternative blood supply and protect tissues from ischemic damage in patients with peripheral artery disease. However, the mechanism of collateral artery development is difficult to validate.Methods and ResultsCollateral arteries were visualized using micro–x‐ray computed tomography. Developmental characteristics were assessed using confocal microscopy. We conducted a single‐center, retrospective, observational study and assessed the dilatation of collateral arteries on ischemic sides. We quantified the vascular volume in both ischemic and nonischemic legs. A prominent increase in vascular volume was observed in the ischemic leg using a murine hind‐limb ischemia model. We also performed qualitative assessment and confirmed that the inferior gluteal artery functioned as a major collateral source. Serial analysis of murine hind‐limb vessel development revealed that the inferior gluteal artery was a remnant of the ischial artery, which emerged as a representative vessel on the dorsal side during hind‐limb organogenesis. We retrospectively analyzed consecutive patients who were admitted for the diagnosis or treatment of peripheral artery disease. The diameter of the inferior gluteal artery on the ischemic side showed significant dilatation compared with that on the nonischemic side.ConclusionsOur findings indicate that an embryonic remnant artery can become a collateral source under ischemic conditions. Flow enhancement in the inferior gluteal artery might become a novel therapeutic approach for patients with peripheral artery disease.

A prostacyclin agonist and an omental flap increased myocardial blood flow in a porcine chronic ischemia model

ObjectiveWe hypothesized that therapeutic efficacy may be augmented by a combination of placing a sheet immersed in ONO-1301SR, a slow-release synthetic prostacyclin agonist-inducing multiproangiogenic cytokines, over the left ventricle and a pedicled omental flap in a chronic myocardial infarct heart. MethodsA minipig chronic myocardial infarction was generated by placing an ameroid constrictor ring around the left anterior descending artery for 4 weeks. The minipigs were then assigned into 4 groups of 6 each: sham, omental flap only, ONO-1301SR only, and ONO-1301SR combined with an omental flap (combined). Four weeks after treatment, therapeutic efficacy was evaluated histologically and via several modalities used in the clinical setting. ResultsIn an angiogram and pressure wire study, the combined group induced development of collateral arteries to decrease the resistance and increase the flow reserve of microvasculature in the left circumflex territory. In a 13N-ammonia positron emission tomography study, the combined group displayed a prominent increase in myocardial blood flow and myocardial flow reserve in the left circumflex territory, particularly at the infarct-border region. Consequently, the combined group showed greater regional cardiac function in the left circumflex territory particularly at the infarct-border region, contributing to a greater global ejection fraction with a smaller left ventricular endosystolic volume. Pathologically, attenuated fibrosis, nonswollen myocytes, and upgraded capillary density and proangiogenic cytokines were prominent in the combined group. ConclusionsONO-1301SR combined with a pedicled omental flap synergistically promoted myocardial angiogenesis, leading to function recovery in a porcine chronic myocardial infarction model.

Coronary autoregulation and assessment of stenosis severity without pharmacological vasodilation.

For identification of myocardial ischaemia by non-invasive imaging or invasive physiological assessment, administration of a vasodilating or positive inotropic agent is often considered indispensable to exhaust the cardiac compensation mechanisms. Indeed, microcirculatory dilatation is needed for assessment of myocardial perfusion or coronary blood flow. However, three different modalities exist that quantify myocardial ischaemia without recourse to pharmacological stress agents, using either myocardial contrast echocardiography, imaging of myocardial blood volume or invasive coronary pressure measurement with the instantaneous wave-free ratio (iFR). The theoretical framework of these vasodilator-free modalities revolves around the two innate mechanisms that protect the myocardium from ischaemia at rest: coronary autoregulation and arteriogenesis. Coronary autoregulation and metabolic dilatation form the putative processes that regulate microvascular tone and constitute of a complex interplay between metabolic factors, myogenic control, and endothelium-based control that each interact with coronary arterioles of a different size. Arteriogenesis describes the development of large calibre collateral arteries from a pre-existing network, triggered by occlusive coronary artery disease. Following these descriptions, the fundamental principles and the existing evidence of these three diagnostic modalities are reviewed. Emphasis is placed on iFR, which is clinically best applicable. Instantaneous wave-free ratio has proven to be an effective method to determine the haemodynamic significance of coronary stenoses in two recent large randomized clinical trials, together enrolling over 4500 patients. Ultimately, this review aims to clarify the theoretical rationale and to describe the clinical implications of functional stenosis assessment under resting conditions.

The relationship between fasting blood glucose variability and coronary artery collateral formation in type 2 diabetes patients with coronary artery disease.

Coronary collaterals are an alternative source of blood supply to ischemic myocardium. Well-developed coronary collateral arteries in patients with coronary artery disease (CAD) limit the size of acute myocardial infarction and improves survival. The aim of this study was to investigate the relationship between glycemic variability and coronary collateral formation in patients with type 2 diabetes mellitus and CAD. Consecutive patients undergoing percutaneous coronary intervention or coronary artery bypass grafting procedures were studied. Multivariate logistic regression models were used to examine the association between coronary artery collateral formation graded by Rentrope classification and glycemic variability, measured by coefficient variation of fasting blood glucose. In our study, we retrospectively enrolled 300 patients, of whom 239 were diabetic (age: 70.1±11.9, 56% men) and 61 were nondiabetic (age: 71.5±11.5, 72% men). Diabetic patients were further stratified as follows: those with poor coronary collateral artery development (n=171, age: 69.7±12.4, 55% men) and those with good coronary collateral artery development (n=68, age 71.1±10.8, 59% men) according to the Rentrope classification. Our findings did not show association between glycemic variability and coronary collateral vessels development after controlling for potential confounders (odds ratio: 2.51; 95% confidence interval: 0.57-11.03; P=0.22). The culprit lesion (≥75% stenosis) in the left anterior descending artery and the right coronary artery was more frequent in the good collateral group compared with the poor collateral group (66 vs. 50%, P=0.02; 63 vs. 45%, P=0.01 respectively). Glycemic variability is not associated with coronary collateral artery formation in patients with type 2 diabetes mellitus and CAD.

Coronary artery dominance dependent collateral development in the human heart.

In obstructive coronary artery disease, coronary collateral arteries serve as alternative conduits for blood flow to the myocardial tissue supplied by the obstructed vessel(s). Therefore, they are a "natural coronary arterial bypass" to the region supplied by the obstructed vessels. This study aims to determine the influence of demographic and morphologic coronary arterial factors on coronary collateral development in coronary arterial obstruction. The study group was selected from the coronary angiographic records of 2029 consecutive patients (mean age: 59 ± 12 years). Coronary collaterals were graded from 0 to 3 based on the collateral connection between the donor and recipient arteries. The angiograms of the patients (n = 286) with total obstruction of the coronary arteries were selected for analysis. There were no significant association between patients' age and sex and the formation of excellent collaterals. However, the location of atherosclerotic lesion affected collateral development in the right coronary artery. In addition, the right coronary arterial dominant pattern significantly influenced the formation of excellent coronary collaterals. Coronary collateral arteries are better developed in right dominant pattern. It may be concluded that coronary arterial morphological pattern influences coronary collateral artery development.

Suppression of ischemia in arterial occlusive disease by JNK-promoted native collateral artery development.

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive sprouting angiogenesis, and defects in developmental vascular morphogenesis. Our analysis demonstrates that the MLK-JNK signaling pathway is a key regulatory mechanism that protects against ischemia in arterial occlusive disease.

Perioperative Major Aortopulmonary Collateral Arteries (MAPCAs) Coiling in Tetralogy of Fallot Patients Undergoing for Total Correction

Background: Tetralogy of Fallot (TOF) is characterized by ventricular septal defect, an overriding aorta, varying degrees of pulmonic stenosis, and right ventricular hypertrophy. It may be associated with a number of lesions including development of major aortopulmonary collateral arteries (MAPCAs) in less than 5% of cases. In this study we just focused on the management of MAPCAs. Methodology: TOF patients with significant MAPCAs were selected after cardiac catheterization and planned for transcatheter embolization just before surgery. Results: A total of 45 patients underwent transcatheter closure of MAPCAs just before surgical correction with 100% success rate. The age varied from 3-30 years and 55% (n=25) were female. In majority 60% (n=27) the procedure was carried out under deep sedation with local anaesthesia while 18 (40%) patients had general anaesthesia. There was insignificant residual leak in 2 (4%) patients, transient bradycardia (n=1) and hypercyanotic spell in 4% (n=2). No serious complications or death occurred during this study period. Conclusion: Transcatheter coiling of MAPCAs is safe, easy, and effective procedure and protects the patient from its long term devastating complications.

5 The cardiac microrna miR-1 induces endothelial cell angiogenesis

Ischaemic heart disease is the leading cause of morbidity and mortality in the Western world. Progression of the disease is associated with the growth and/or episodic rupture of atherosclerosis lesions leading to narrowing or occlusion of major coronary arteries. Arterial occlusion activates sprouting of pre-existing capillaries (angiogenesis) and the development of collateral arteries (arteriogenesis) to protect the myocardial tissue against the ischaemic condition. Unfortunately, the molecular mechanisms that control post-ischaemic neovascularization of the heart are large unknown. Emerging evidence indicates that acute ischaemia in patients with ST-segment-elevation myocardial infarction induces the release of microRNA miR-1 from injured cardiomyocytes. miRNA-1 promotes physiological angiogenesis during the embryogenesis of zebra fish but its role in post-natal angiogenesis in human endothelial cells has not been studied thus far. In this work, we show that adenoviral-mediated delivery of miR-1 into primary Human Umbilical Vein Endothelial Cells (HUVECs) resulted in an increase in proliferation, migration and the ability of the cells to form tubular-like structures in in vitro matrigel assays. These results suggest that cardiac microRNAs released by ischaemic cardiomyocytes might activate angiogenic events in neighbouring endothelial cells to promote the formation of new blood vessels. Thus, therapeutic interventions aimed to potentiate this process might have important clinical applications to facilitate fast perfusion of the infarcted heart. Acknowledgments This work was supported by RIHS, The Wolverhampton Coronary Aftercare Support Group (WCASG) Charity, and The Rotha Abraham Bequest Charity.