Chronic limb-threatening ischemia could benefit from growth hormone therapy for wound healing and limb salvage

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Abstract

Revascularization for chronic limb-threatening ischemia (CLTI) is necessary to alleviate symptoms and wound healing. When it fails or is not possible, there are few alternatives to avoid limb amputation in these patients. Although experimental studies with stem cells and growth factors have shown promise, clinical trials have demonstrated inconsistent results because CLTI patients generally need arteriogenesis rather than angiogenesis. Moreover, in addition to the perfusion of the limb, there is the need to improve the neuropathic response for wound healing, especially in diabetic patients. Growth hormone (GH) is a pleiotropic hormone capable of boosting the aforementioned processes and adds special benefits for the redox balance. This hormone has the potential to mitigate symptoms in ischemic patients with no other options and improves the cardiovascular complications associated with the disease. Here, we discuss the pros and cons of using GH in such patients, focus on its effects on peripheral arteries, and analyze the possible benefits of treating CLTI with this hormone.

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Most cited references 119

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Peripheral arterial disease detection, awareness, and treatment in primary care.

Alan Hirsch (2001)

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that is common and is associated with an increased risk of death and ischemic events, yet may be underdiagnosed in primary care practice. To assess the feasibility of detecting PAD in primary care clinics, patient and physician awareness of PAD, and intensity of risk factor treatment and use of antiplatelet therapies in primary care clinics. The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, a multicenter, cross-sectional study conducted at 27 sites in 25 cities and 350 primary care practices throughout the United States in June-October 1999. A total of 6979 patients aged 70 years or older or aged 50 through 69 years with history of cigarette smoking or diabetes were evaluated by history and by measurement of the ankle-brachial index (ABI). PAD was considered present if the ABI was 0.90 or less, if it was documented in the medical record, or if there was a history of limb revascularization. Cardiovascular disease (CVD) was defined as a history of atherosclerotic coronary, cerebral, or abdominal aortic aneurysmal disease. Frequency of detection of PAD; physician and patient awareness of PAD diagnosis; treatment intensity in PAD patients compared with treatment of other forms of CVD and with patients without clinical evidence of atherosclerosis. PAD was detected in 1865 patients (29%); 825 of these (44%) had PAD only, without evidence of CVD. Overall, 13% had PAD only, 16% had PAD and CVD, 24% had CVD only, and 47% had neither PAD nor CVD (the reference group). There were 457 patients (55%) with newly diagnosed PAD only and 366 (35%) with PAD and CVD who were newly diagnosed during the survey. Eighty-three percent of patients with prior PAD were aware of their diagnosis, but only 49% of physicians were aware of this diagnosis. Among patients with PAD, classic claudication was distinctly uncommon (11%). Patients with PAD had similar atherosclerosis risk factor profiles compared with those who had CVD. Smoking behavior was more frequently treated in patients with new (53%) and prior PAD (51%) only than in those with CVD only (35%; P <.001). Hypertension was treated less frequently in new (84%) and prior PAD (88%) only vs CVD only (95%; P <.001) and hyperlipidemia was treated less frequently in new (44%) and prior PAD (56%) only vs CVD only (73%, P<.001). Antiplatelet medications were prescribed less often in patients with new (33%) and prior PAD (54%) only vs CVD only (71%, P<.001). Treatment intensity for diabetes and use of hormone replacement therapy in women were similar across all groups. Prevalence of PAD in primary care practices is high, yet physician awareness of the PAD diagnosis is relatively low. A simple ABI measurement identified a large number of patients with previously unrecognized PAD. Atherosclerosis risk factors were very prevalent in PAD patients, but these patients received less intensive treatment for lipid disorders and hypertension and were prescribed antiplatelet therapy less frequently than were patients with CVD. These results demonstrate that underdiagnosis of PAD in primary care practice may be a barrier to effective secondary prevention of the high ischemic cardiovascular risk associated with PAD.

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The role of substance P in inflammatory disease.

Terence M. O'Connor, Joseph O'Connell, Darren O'Brien … (2004)

The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease. Copyright 2004 Wiley-Liss, Inc.

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Wound Healing: An Overview

Christopher Attinger, Jeffrey E. Janis, George Broughton (2006)

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Author and article information

Contributors

Diego Caicedo:

ORCID: https://orcid.org/0000-0002-9599-7047

Pablo Devesa

Víctor M. Arce

Julia Requena

Journal

Journal ID (nlm-ta): Ther Adv Cardiovasc Dis

Journal ID (iso-abbrev): Ther Adv Cardiovasc Dis

Journal ID (publisher-id): TAK

Journal ID (hwp): sptak

Title: Therapeutic advances in cardiovascular disease

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Print): 1753-9447

ISSN (Electronic): 1753-9455

Publication date (Electronic): 22 December 2017

Publication date (Print): February 2018

Volume: 12

Issue: 2

Pages: 53-72

Affiliations

[1-1753944717745494]Department of Angiology and Vascular Surgery, Complexo Hospitalario Universitario de Pontevedra, Avda. de Mourente, s/n; 36071-Pontevedra, Spain

[2-1753944717745494]Research and Development Medical Center Foltra, Teo, Spain

[3-1753944717745494]Department of Physiology, Santiago University School of Medicine, Spain

[4-1753944717745494]Department of Angiology and Vascular Surgery, Complexo Hospitalario Universitario de Pontevedra, Spain

[5-1753944717745494]Scientific Direction, Medical Center Foltra. Travesía Montouto, 24; 15710-Teo, A Coruña, 15886, Spain

Author notes

[*] diego.caicedo.valdes@ 123456sergas.es

[*] jesus.devesa@ 123456usc.es

Author information

Diego Caicedo https://orcid.org/0000-0002-9599-7047

Article

Publisher ID: 10.1177_1753944717745494

DOI: 10.1177/1753944717745494

PMC ID: 5772430

PubMed ID: 29271292

SO-VID: 0b14b4d6-a54d-4db6-ac55-08c1808a27ae

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

Chronic limb-threatening ischemia could benefit from growth hormone therapy for wound healing and limb salvage

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Abstract

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Cardiovascular Innovations and Applications

Most cited references 119

Peripheral arterial disease detection, awareness, and treatment in primary care.

The role of substance P in inflammatory disease.

Wound Healing: An Overview

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