Marriage of resistance and conduit arteries breeds critical limb ischemia

Coats, Paul; Wadsworth, R. M.

doi:10.1152/ajpheart.00773.2004

Cited by 48 publications

(39 citation statements)

References 83 publications

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“…Other studies (34,56) have shown that perfusion subsequent to femoral artery occlusion is not correlated with capillarity. Studies have shown that chronic reductions in flow and pressure can result in enhanced constriction and inward remodeling characterized by wall thinning (1,6,8,17,19,41,49,50,64,67), characteristics that occur in human critical limb ischemia (17)(18)(19). Thus, the profound decrease in distal microvascular flow and pressure could result in similar decompensatory events in the precapillary arterioles and small arteries that control the majority of microvascular resistance (3,27,42,77).…”

Section: Discussionmentioning

confidence: 99%

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth

Distasi

Case

Ziegler

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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arteriogenesis; hindlimb ischemia; necrosis; regeneration; NADPH oxidase 2 IN THE PERIPHERAL CIRCULATION, the dilation and enlargement of preexisting vessels that form collateral pathways subsequent to arterial occlusion are the primary vascular compensations that preserve tissue viability and maintain function. These vessels dilate within seconds (25,39,45,70) and undergo expansion for weeks (20,25,45,69). In various species, the preexisting vessels are the size of the smallest arteries, and they enlarge ϳ100% (14,20,35,45,56). Available clinical studies have indicated that subsequent to arterial occlusion in the peripheral circulation, the primary vessels that enlarge as collaterals are preexisting arteries (4,29,57). The largest of the preexisting vessels are typically those that become the dominant collaterals (35,45,51). Combined anatomic and modeling studies have predicted that hindlimb flow subsequent to femoral artery occlusion is primarily determined by these collaterals (22,56). This is consistent with studies of segmental resistances that demonstrated that compensation in the collateral vessels is of significantly greater hemodynamic importance than adaptations in the distal microvasculature (43,71,75). Nevertheless, few studies investigating the mechanisms of vascular compensation subsequent to arterial occlusion in mice have specifically identified and studied these preexisting vessels that form the primary collateral pathways. Such investigations are needed because angiogenesis and collateral growth are initiated by different stimuli, and differences exist in the molecules and mechanisms that mediate these important processes (7, 11).Leukocytes, especially lymphocytes (63, 74) and macrophages (2,33,37), have been shown to have an important role in vascular compensation to hindlimb ischemia. Recent studies by Tojo et al. (66) and Urao et al. (72) have established that NADPH oxidase 2 (Nox2)-derived ROS from bone marrowderived cells (BMDCs) have an important role in neovascularization in the ischemic mouse hindlimb. The initial report (66) concluded from microsphere data that collateral growth was impaired, but did not specifically identify collateral bypass vessels or measure their diameters.To investigate the hypothesis that Nox2-derived NAD(P)H oxidase mediates primary collateral growth subsequent to arterial occlusion, the present study used Rac2-null (Rac2 Ϫ/Ϫ ) and Nox2-null (Nox2 Ϫ/Ϫ ) mice and a novel method of identifying primary hindlimb collaterals. Rac2 is expressed primarily, if not exclusively, in hematopoietic cells (38, 52) and binds to and activates Nox2-containing NAD(P)H oxidase (24,40). In addition, leukocytes from Rac2 Ϫ/Ϫ and Nox2 Ϫ/Ϫ mice have impaired function related to reduced ROS production (47,66,72). We present a method to identify the dominant or primary collateral that should be the major collateral supplying flow to

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Section: Discussionmentioning

confidence: 99%

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth

Distasi

Case

Ziegler

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Tissue necrosis occurs when the ischemic milieu established in the absence of straight line flow to the foot eventually exhausts compensatory mechanisms such as ischemic preconditioning of the limb and development of collaterals. 6 Markers of inflammation (such as interleukin-6, tumor necrosis factor alpha and C-reactive protein) and platelet activation are increased in patients with CLI compared with normal individuals. 7,8 Endovascular therapy for critical limb ischemia…”

Section: Pathophysiology Of Critical Limb Ischemiamentioning

confidence: 99%

Endovascular therapy for critical limb ischemia

Arain

White

2008

Vasc Med

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Chronic critical limb ischemia (CLI) occurs when arterial perfusion is reduced below a threshold level that results in rest pain and/or tissue breakdown in the lower extremities. Importantly, it is associated with high cardiovascular morbidity and mortality. Without prompt revascularization, CLI may result in loss of a limb (i.e. amputation) and/or life. The goal of endovascular therapy is the re-establishment of pulsatile, straight-line flow to the distal extremity. Percutaneous transluminal angioplasty (PTA) has been shown to be effective and safe in the setting of CLI, with limb salvage rates that compare favorably with surgical procedures. Stents are indicated for failed PTA, while adjunctive therapies such as lasers, thermal angioplasty and atherectomy devices lack data demonstrating improved efficacy compared with conventional lower extremity interventions. In addition to successful revascularization, the institution of lifestyle changes, atherosclerotic risk factor modification, and pharmacologic therapies are indicated to reduce cardiovascular morbidity and mortality.

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“…24,25 These responses fail to supply the necessary amount of blood flow and oxygen to the limb, causing arterioles in patients with CLI to become maximally vasodilated and insensitive to provasodilatory stimuli. 25 This phenomenon, referred to as vasomotor paralysis, is thought to be the result of chronic exposure to vasorelaxing factors Severe claudication 4…”

Section: Epidemiology and Natural Historymentioning

confidence: 99%

Critical limb ischemia

Varu

Hogg

Kibbe

2010

Journal of Vascular Surgery

312

249

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Critical limb ischemia (CLI) continues to be a significantly morbid disease process for the aging population. Rigid guidelines for the management of patients with CLI are inappropriate due to the complexities that are involved in optimally treating these patients. A thin line exists in the decision process between medical management vs surgical management by revascularization or amputation, and the perception of "success" in this patient population is evolving. This review explores these issues and examines the challenges the treating physician will face when managing the care of patients with CLI. The epidemiology and natural history of CLI is discussed, along with the pathophysiology of the disease process. A review of the literature in regards to the different treatment modalities is presented to help the physician optimize therapy for patients with CLI. New scoring systems to help predict outcomes in patients with CLI undergoing revascularization or amputation are discussed, and an overview of the current status of patient-oriented outcomes is provided. Finally, we briefly examine emerging therapies for the treatment of CLI and provide an algorithm to help guide the practicing physician on how to approach the critically ischemic limb with regard to the complicated issues surrounding these patients.

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Marriage of resistance and conduit arteries breeds critical limb ischemia

Abstract: Coats, Paul, and Roger Wadsworth. Marriage of resistance and conduit arteries breeds critical limb ischemia.

Cited by 48 publications

References 83 publications

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth

Endovascular therapy for critical limb ischemia

Critical limb ischemia

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Marriage of resistance and conduit arteries breeds critical limb ischemia

Abstract: Coats, Paul, and Roger Wadsworth. Marriage of resistance and conduit arteries breeds critical limb ischemia.

Cited by 48 publications

References 83 publications

Suppressed hindlimb perfusion in Rac2−/− and Nox2−/− mice does not result from impaired collateral growth

Suppressed hindlimb perfusion in Rac2−/− and Nox2−/− mice does not result from impaired collateral growth

Endovascular therapy for critical limb ischemia

Critical limb ischemia

Contact Info

Product

Resources

About

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth