Diabetic foot cellular hypoxia may be due to capillary shunting – A novel hypothesis

Gabbay, Itay E.; Gabbay, Merav; Gabbay, Uri

doi:10.1016/j.mehy.2013.11.005

Cited by 12 publications

(13 citation statements)

References 21 publications

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“…The higher in-vivo RBC aggregation found concomitantly with higher shear rates (favoring the breaking down of reversible aggregates) in the diabetic population, for both cephalic and great saphenous veins, also support the hypothesis that enhanced RBC aggregating energies were determinant for explaining reported observations. The exact mechanism for the higher shear rate in veins of diabetic patients compared to the control population is unknown but might be associated with 1) a hemodynamic compensation phenomenon to avoid the deleterious effect of large flowing aggregates (inducing high blood viscosity) on the venous return, or 2) an arteriovenous shunting phenomenon that has already been described elsewhere [ 26 ]. We indeed observed higher mean velocities in the diabetic population ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Venous Assessment of Red Blood Cell Aggregate Sizes in Diabetic Patients with a Quantitative Cellular Ultrasound Imaging Method: Proof of Concept

et al. 2015

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BackgroundDiabetic patients present higher level of red blood cell (RBC) aggregation contributing to the development of vascular complications. While it has been suggested that this hematology/rheology parameter could bring additional prognostic information for the management of those patients, RBC aggregation screening is not included as a clinical practice. Most medical centers are not equipped to measure properly this parameter, although sedimentation tests can bring some indication. Here, we aimed at evaluating the feasibility of using ultrasound to assess in-vivo hyper-aggregation in type 2 diabetic patients.Research design and methodsSeventeen diabetic patients and 15 control subjects underwent ultrasound measurements of RBC aggregation in both cephalic and great saphenous veins. Non-invasive in-vivo ultrasound measurements were performed using a newly developed cellular imaging technique, the structure factor size and attenuation estimator (SFSAE). Comparisons with an ex-vivo gold standard rheometry technique were done, along with measurements of pro-aggregating plasma molecule concentrations.Results In-vivo RBC aggregation was significantly higher in diabetic patients compared with controls for cephalic vein measurements, while a trend (p = 0.055) was noticed in the great saphenous vein. SFSAE measurements were correlated with gold standard in-vitro measures, fibrinogen and C-reactive protein plasma concentrations.ConclusionRBC aggregation can be measured in-vivo in diabetic patients using ultrasound. Prospective studies are needed to determine whether the SFSAE method could help clinicians in the early management of vascular complications in this patient population.

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Section: Discussionmentioning

confidence: 99%

“…Specific flowing conditions could have impaired measurements in this foot area. Indeed, arteriovenous shunting has been proposed as a key factor of foot gangrene development in diabetic patients [ 26 ]. Such phenomena may have promoted unfavorable high shear flow conditions for the formation of RBC aggregates in this group.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Venous Assessment of Red Blood Cell Aggregate Sizes in Diabetic Patients with a Quantitative Cellular Ultrasound Imaging Method: Proof of Concept

et al. 2015

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“…The resulting loss of vasoconstrictor tone and peripheral vasodilatation gives rise to the appearance of a warm, oedematous neuropathic foot [ 60 ]. The high peripheral blood flow passes through arteriovenous shunts [ 60 ], and it was recently hypothesised that excessive microvascular shunting may give rise to tissue hypoxia, despite the high blood flow [ 61 ]. Our model of oxygen extraction in tissue [ 13 ] supports this notion, and predicts that failure to suppress blood flow in capillary dysfunction can be the source of severe oxidative stress, microvascular injury and pain [ 59 ].…”

Section: Sources Of Pain In Diabetic Neuropathymentioning

confidence: 99%

The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy

et al. 2014

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Diabetic neuropathy is associated with disturbances in endoneurial metabolism and microvascular morphology, but the roles of these factors in the aetiopathogenesis of diabetic neuropathy remain unclear. Changes in endoneurial capillary morphology and vascular reactivity apparently predate the development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early experimental diabetes, and of unaffected blood flow when early histological signs of neuropathy first develop in humans. We recently showed that disturbances in capillary flow patterns, so-called capillary dysfunction, can reduce the amount of oxygen and glucose that can be extracted by the tissue for a given blood flow. In fact, tissue blood flow must be adjusted to ensure sufficient oxygen extraction as capillary dysfunction becomes more severe, thereby changing the normal relationship between tissue oxygenation and blood flow. This review examines the evidence of capillary dysfunction in diabetic neuropathy, and whether the observed relation between endoneurial blood flow and nerve function is consistent with increasingly disturbed capillary flow patterns. The analysis suggests testable relations between capillary dysfunction, tissue hypoxia, aldose reductase activity, oxidative stress, tissue inflammation and glucose clearance from blood. We discuss the implications of these predictions in relation to the prevention and management of diabetic complications in type 1 and type 2 diabetes, and suggest ways of testing these hypotheses in experimental and clinical settings.

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“…Pathophysiological mechanisms predisposing to formation of tissue alteration include generation of advanced glycation end-products (AGEs) or glycotoxins and action of advanced lipoxidation products (ALEs) either of dietary origin or from intracellular sources (Gabbay et al, 2014). As potent prooxidants, they increase the intracellular oxidative stress, deplete the anti-oxidant reserve, and induce an inflammatory reaction.…”

mentioning

confidence: 99%

“…red meat) and prescription of drugs with antioxidant properties (Kang et al, 1998; Corathers et al, 2013; Kim and Steinberg, 2013). Gabbay et al (2014) hypothesize that the tissue blood flow in diabetic foot is rerouted through the metarteriole thoroughfare channel, bypassing the exchange capillaries (Gabbay et al, 2014). This disables the nutrient and oxygen exchange in tissues and results in local hypoxia.…”

mentioning

confidence: 99%

Perioperative management of diabetic foot

Soghomonyan¹

2014

Front. Pharmacol.

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Diabetic foot cellular hypoxia may be due to capillary shunting – A novel hypothesis

Cited by 12 publications

References 21 publications

In Vivo Venous Assessment of Red Blood Cell Aggregate Sizes in Diabetic Patients with a Quantitative Cellular Ultrasound Imaging Method: Proof of Concept

In Vivo Venous Assessment of Red Blood Cell Aggregate Sizes in Diabetic Patients with a Quantitative Cellular Ultrasound Imaging Method: Proof of Concept

The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy

Perioperative management of diabetic foot

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