Minimising failure in critical lower limb ischaemia intervention: Adjuvant capillary bed recruitment is the missed opportunity

Abstract

Critical limb ischaemia is the end stage of peripheral arterial disease before limb loss. Contemporary interventions to restore blood flow have high morbidity and mortality and fail to provide sustained restoration of peripheral circulation. Cell-based therapies designed to promote neovascularisation or angiogenesis have been shown in trials to be safe but clinically ineffective. Notwithstanding endless research in the area, no headway has been made in identifying a successful therapy designed specifically to target muscle disease in critical lower limb ischaemia. Thus, the quest to find an effective, lasting solution for critical lower limb ischaemia continues and requires more innovative therapeutic tactics. Our aim is to highlight the crucially interlinked role of the capillary bed, skeletal muscle mass and mitochondria in critical lower limb ischaemia patients and to identify novel therapeutic mechanisms that the vascular interventionalist can add to their armamentarium.

An Observational Clinical Trial Examining the Effect of Topical Oxygen Therapy (Natrox™) on the Rates of Healing of Chronic DiAbetic Foot Ulcers (OTONAL Trial)

“…Currently, there is no surgical treatment to improve the micro-circulation of the foot among patients with MVD. Therefore, non-surgical treatments should be considered and trialed early once subtypes of CLTI involving MVD are established including TOT, 26 the rationale being that if oxygen delivery cannot be achieved from the vasculature, then it can be given directly onto the wound. The addition of TOT to SOC dressings has increased the DFU proportion healed at 3 months in several recently reported randomized controlled trials and OTONAL gives further credence to the efficacious role of TOT to close hard-to-heal chronic DFUs.…”

Role of Adipose Tissue and Skeletal Muscle in Atherosclerosis and in Central Hemodynamics

“…The preliminary data of this research project seems to suggest that CLI patients have SM dysfunction, with loss of muscle strength and density. The loss of muscle strength (measured from hand grip) is associated, according to the literature with arte rial stiffness, inflammation, endothelial dysfunction and allcause mortality including cardiovascular mortality [12,32,33]. Muscle strength has been shown to be more relevant than muscle quantity [32].…”

“…The loss of muscle strength (measured from hand grip) is associated, according to the literature with arte rial stiffness, inflammation, endothelial dysfunction and allcause mortality including cardiovascular mortality [12,32,33]. Muscle strength has been shown to be more relevant than muscle quantity [32]. A crosssectional study of cohort of 208 individuals, of ages of 80 years old and older, demonstrated that reduction of muscle mass and strength were associated with atherosclerosis and endothelial dysfunction [16].…”