Marriage of resistance and conduit arteries breeds critical limb ischemia

2005 ◽  
Vol 288 (3) ◽  
pp. H1044-H1050 ◽  
Author(s):  
Paul Coats ◽  
Roger Wadsworth
Keyword(s):  
Blood Supply ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Sudden Increase ◽  
Large Artery ◽  
Resistance Arteries ◽  
Tissue Edema ◽  
Surgical Bypass ◽  
Small Resistance ◽  
And Function

Atherosclerosis in a major leg artery leads to impaired blood supply, which normally progresses to critical limb ischemia. Atherosclerosis produces substantial alterations of structure and endothelial function in the large conduit arteries. Pressure unloading and ischemia in the distal vasculature bring about alterations in microvascular function. Resistance arteries undergo significant wall thinning and changes in their contractile regulation. Optimization of large artery dimensions by the small arteries through flow-mediated vasodilation is impaired. Angiogenesis is stimulated, which can result in the formation of major collateral feeder vessels in addition to small nutritive blood vessels. However, angiogenesis can also contribute to instability of atherosclerotic plaques, which ultimately leads to further deterioration in blood supply. Surgical bypass grafting to restore blood supply to the distal leg generates a sudden increase of pressure in the weakened resistance vasculature, leading to uncontrolled changes in capillary hydrostatic pressure, extravasation of fluid, and tissue edema. This review aims to highlight the importance of the resistance vasculature in critical limb ischemia and the interdependence of pathophysiological changes in the large conduit and small resistance arteries. The major unresolved question is why the physiological mechanisms that regulate vascular structure and function ultimately break down, leading to circulatory failure within the distal limb.

Abstract 119: Potential Role for Bone Marrow Niche and Endothelial Progenitor Cell Dysfunction in Critical Limb Ischemia

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Martin Teraa ◽  
Ralf W Sprengers ◽  
Frans L Moll ◽  
Marianne C Verhaar ◽  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Progenitor Cell ◽  
Limb Ischemia ◽  
Endothelial Damage ◽  
Inverse Association ◽  
Healthy Controls ◽  
Endothelial Progenitor ◽  
And Function

Background Critical limb ischemia (CLI) is characterized by obstruction of lower extremity arteries and a largely unexplained impaired ischemic neovascularization response. Bone marrow (BM) derived endothelial progenitor cells (EPC) contribute to postnatal neovascularization. We hypothesize that reduced levels and function of circulating progenitor cells and a dysfunctional BM environment contribute to impaired neovascularization in CLI. Methods Levels of primitive (CD34+ and CD133+) progenitors and CD34+KDR+ haemangioblastic EPC were analyzed using flow cytometry in peripheral blood (PB) and BM from 101 CLI patients in the JUVENTAS trial ( NCT00371371 ) and healthy controls (n=37 and n=12 for PB and BM, respectively). Endothelial damage markers (sE-selectin, sICAM-1, sVCAM-1, thrombomodulin) and PB levels of progenitor cell mobilizing (VEGF, SDF-1α, SCF, G-CSF) and inflammatory (IL-6, IL-8, IP-10) factors were assessed by ELISA and multiplex. Levels and activity of the EPC mobilizing protease MMP-9 were assessed in BM plasma by ELISA and zymography. Circulating angiogenic cells (CAC) were cultured from PB, and CAC paracrine function was assessed. Results Endothelial damage markers were higher in CLI ( p< 0.01). PB levels of VEGF, SDF-1α, SCF, G-CSF ( p< 0.05) and of IL-6, IL-8 and IP-10 were higher in CLI ( p< 0.05). Circulating EPC and CD133+ cells and BM CD34+ cells were significantly lower in CLI (all p <0.05), BM levels and activity of MMP-9 were lower in CLI (both p< 0.01). Multivariate regression analysis showed an inverse association between IL-6 levels and BM CD34+ cell levels ( p= 0.007). CAC outgrowth did not differ significantly between CLI patients and healthy controls ( p= 0.137), however CAC from CLI patients had profoundly reduced migration stimulating potential ( p< 0.0001). Conclusion CLI patients have reduced levels of circulating EPC despite profound endothelial injury and an EPC mobilizing response. Moreover, CLI patients have lower BM CD34+ cell levels, which were inversely associated with the inflammatory marker IL-6, and lower BM MMP-9 levels and activity. Our data suggest that reduced levels and function of circulating progenitor cells and BM dysfunction contribute to the defective neovascularization response in CLI.

Effects of intravenous prostaglandin E1 on arterial compliance: a randomized controlled trial

VASA ◽  
2004 ◽  
Vol 33 (3) ◽  
pp. 131-136 ◽  
Author(s):  
Mlekusch ◽  
Schillinger ◽  
Sabeti ◽  
Al-Awami ◽  
Gschwandtner ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Critical Limb Ischemia ◽  
Arterial Compliance ◽  
Controlled Trial ◽  
Limb Ischemia ◽  
Prostaglandin E ◽  
Large Artery ◽  
Small Artery ◽  
Randomized Controlled ◽  
Intravenous Application

Background: Prostanoids are in widespread use for the treatment of critical limb ischemia and are suggested to improve arterial compliance. However, dose- and time-dependency of these drug effects are indeterminate. We investigated the influence of intravenous application of prostanoids on arterial compliance parameters in patients with critical limb ischemia due to peripheral artery disease (PAD). Patients and methods: We included 82 consecutive patients with PAD Fontaine stage III and IV in a patient-blinded, randomized controlled trial. Patients were randomly assigned to either single dose intravenous treatment with 40 mug (n = 29) or 60 mug (n = 27) of Alprostadil (PGE1) in 250 ml 0.9% saline over 2 hours, or 250 ml 0.9% saline solution as a placebo group (n = 26). Large and small artery compliance was measured by peripheral pulse contour analysis at baseline, at one hour during intravenous infusion of Alprostadil, immediately after and 24 hours after the end of the infusion. For study purpose the patients received Alprostadil only once during the observation period of 2 days. Results: Large artery compliance, blood pressure, heart rate and cardiac output were unaffected by PGE1 administration irrespectively of drug-dosage or time interval. Small artery compliance increased at 1 hour during intravenous application of Alprostadil (40 mug Alprostadil p = 0.001; 60 mug Alprostadil p < 0.0001) compared to placebo and increased median +47% (IQR +5% to +100%) after administration of 40 mug Alprostadil and median +32% (IQR –11% to +88%) after 60 mug Alprostadil (p = 0.5). Immediately after the end of Alprostadil infusion small artery compliance decreased to baseline levels. Conclusions: Prostaglandin E1 causes a significant improvement of small artery compliance during the time of intravenous application. However, this effect rapidly diminishes after the end of administration and no dose-dependency between 40 mug and 60 mug Alprostadil is observed.

scholarly journals Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension

2015 ◽  
Vol 38 (6) ◽  
pp. 394 ◽  
Author(s):  
Ernesto L Schiffrin
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Clinical Investigation ◽  
Antihypertensive Agents ◽  
Tissue Perfusion ◽  
Vascular Wall ◽  
Resistance Arteries ◽  
Small Arteries ◽  
Small Resistance ◽  
And Function

This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

scholarly journals Endovascular 30-day Outcomes for Critical Limb Ischemia Are Improving in Recent Years Relative to Surgical Bypass Grafting

2020 ◽  
Vol 72 (1) ◽  
pp. e133-e134
Author(s):  
Christopher A. Latz ◽  
Laura T. Boitano ◽  
Linda J. Wang ◽  
Anna A. Pendleton ◽  
Brandon J. Sumpio ◽  
...  
Keyword(s):  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Bypass Grafting ◽  
Surgical Bypass

scholarly journals Improvement in Blood Supply After “Heparin-Dextran” Therapy in Patients of Buerger’s Disease with Critical Limb Ischemia

2012 ◽  
Vol 75 (6) ◽  
pp. 462-468 ◽  
Author(s):  
Sanand Bag ◽  
Arunanshu Behera ◽  
Niranjan Khandelwal ◽  
J. R. Bapuraj ◽  
Rakesh Kumar Vasishta
Keyword(s):  
Blood Supply ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Buerger’S Disease ◽  
Buerger's Disease

Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

Hypertension ◽  
2022 ◽  
Author(s):  
Stephane Laurent ◽  
Claudia Agabiti-Rosei ◽  
Rosa Maria Bruno ◽  
Damiano Rizzoni
Keyword(s):  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Vicious Circle ◽  
Large Artery ◽  
Resistance Arteries ◽  
Cross Link ◽  
Small Artery ◽  
Structural Abnormalities ◽  
Small Resistance

Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.

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