Claudication induces systemic capillary endothelial swelling

Hickey, N C; Hudlická, O; Simms, M.H.

doi:10.1016/s0950-821x(05)80092-1

Cited by 30 publications

(14 citation statements)

References 9 publications

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“…Interestingly, biopsies from muscles proximal to the site of the bypass showed similar structural changes, indicating that the EC swelling of capillaries is a systemic effect not directly related to ischemia (47). Similarly, in a rodent model of experimentally induced ischemia, ligation of the femoral artery was accompanied by substantial swelling of the capillary EC in skeletal muscles of the hindlimb (14,23,27). Amiloride (a Na ϩ /H ϩ exchange blocker) and to a lesser extent allopurinol (a xanthine oxidase inhibitor), but not vitamin E, prevented this reaction of the capillary system suggesting that EC swelling is related to acidosis (29).…”

Section: Discussionmentioning

confidence: 93%

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Baum

Torchetti

Malik

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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(PAD). Impaired limb blood flow is a major casual factor of lower exercise tolerance in PAD but cannot entirely explain it. We hypothesized that IC is associated with structural changes of the capillary-mitochondria interface that could contribute to the reduction of exercise tolerance in IC patients. Capillary and mitochondrial morphometry were performed after light and transmission electron microscopy using vastus lateralis muscle biopsies of 14 IC patients and 10 age-matched controls, and peak power output (PPO) was determined for all participants using an incremental single-leg kneeextension protocol. Capillary density was lower (411 Ϯ 90 mm Ϫ2 vs. 506 Ϯ 95 mm Ϫ2 ; P Յ 0.05) in the biopsies of the IC patients than in those of the controls. The basement membrane (BM) around capillaries was thicker (543 Ϯ 82 nm vs. 423 Ϯ 97 nm; P Յ 0.01) and the volume density of mitochondria was lower (3.51 Ϯ 0.56% vs. 4.60 Ϯ 0.74%; P Յ 0.01) in the IC patients than the controls. In the IC patients, a higher proportion of capillaries appeared with collapsed slit-like lumen and/or swollen endothelium. PPO was lower (18.5 Ϯ 9.9 W vs. 33.5 Ϯ 9.4 W; P Յ 0.01) in the IC patients than the controls. We suggest that several structural alterations in skeletal muscle, either collectively or separately, contribute to the reduction of exercise tolerance in IC patients. capillary; morphometry; peripheral arterial disease; skeletal muscle; transmission electron microscopy PERIPHERAL ARTERIAL DISEASE (PAD) is an atherosclerotic disease characterized by stenosis or occlusion of the conduit arteries of the lower limbs (20,36). Risk factors associated with PAD include advancing age, cigarette smoking, diabetes mellitus, arterial hypertension, and disturbances in lipid metabolism (12). While many PAD patients are asymptomatic, the arterial narrowing leads to ischemia and hypoxia of the supplied tissues and in severe cases, this manifests as critical limb ischemia (CLI), usually requiring surgical interventions. Intermittent claudication (IC), which is typically described as a cramp-like muscle pain during exercise, is the most commonly reported symptom of PAD and is usually the first noted symptom of the disease.Patients with IC have limited muscular strength and endurance capacities (35), reduced cardiorespiratory fitness (V O 2 peak ), and demonstrate reduced oxygen uptake kinetics at the onset of exercise (6). They also exhibit a significantly reduced tolerance for physical activities such as walking and cycling (2, 13). This reduction in exercise tolerance leads to functional impairments that are similar to those observed in patients with heart failure (31) and contributes to their impaired mobility, reduced quality of life, and elevated risk for the development of cardiovascular complications (17).Impaired limb blood flow is commonly assumed to be the main casual factor of the reduction in exercise tolerance in PAD but cannot entirely explain it. For example, restoration of blood flow capacity with percutaneous endovascular revascularizat...

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Section: Discussionmentioning

confidence: 93%

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Baum

Torchetti

Malik

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…42,43 This overall reduction in blood volume may also contribute to the decrease in the ⌬T2* change.…”

Section: Discussionmentioning

confidence: 99%

Blood Oxygenation Level–Dependent Magnetic Resonance Imaging of the Skeletal Muscle in Patients With Peripheral Arterial Occlusive Disease

et al. 2006

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Background-Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has been used to measure T2* changes in skeletal muscle tissue of healthy volunteers. The BOLD effect is assumed to primarily reflect changes in blood oxygenation at the tissue level. We compared the calf muscle BOLD response of patients with peripheral arterial occlusive disease (PAOD) to that of an age-matched non-PAOD group during postischemic reactive hyperemia. Methods and Results-PAOD patients (nϭ17) with symptoms of intermittent calf claudication and an age-matched non-PAOD group (nϭ11) underwent T2*-weighted single-shot multiecho planar imaging on a whole-body magnetic resonance scanner at 1.5 T. Muscle BOLD MRI of the calf was performed during reactive hyperemia provoked by a cuff-compression paradigm. T2* maps were generated with an automated fitting procedure. Maximal T2* change (⌬T2* max ) and time to peak to reach ⌬T2* max for gastrocnemius, soleus, tibial anterior, and peroneal muscle were evaluated. Compared with the non-PAOD group, patients revealed significantly lower ⌬T2* max -values, with a mean of 7.3Ϯ5.3% versus 13.1Ϯ5.6% (PϽ0.001), and significantly delayed time-to-peak values, with a mean of 109.3Ϯ79.3 versus 32.2Ϯ13.3 seconds (PϽ0.001). Conclusions-T2* time courses of the muscle BOLD MRI signal during postocclusive reactive hyperemia revealed statistically significant differences in the key parameters (⌬T2* max ; time to peak) in PAOD patients compared with age-matched non-PAOD controls.

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“…Microvascular injury distant to lower limb ischaemia has previously been reported in lung [21], kidneys [22], and rat muscle [4,23], but ultrastructural evidence of this occurring in human muscle has not, to the best of our knowledge, been previously reported. The extent to which this may impact on perioperative cardiac, cerebral, and renal complica tions during operations where reperfusion occurs requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Muscle Ischaemia and Iloprost during Femorodistal Reconstruction on Capillary Endothelial Swelling

Egginton

et al. 1996

Int J Microcirc

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In a placebo-controlled trial skeletal muscle biopsies were taken proximal and distal to the site of arterial stenosis, before cross-clamp and 20 min following reperfusion, in 8 well-matched critical limb ischaemia patients undergoing femorodistal bypass. Capillary endothelial swelling – a sign of reperfusion injury – was assessed following infusion with iloprost, a prostacyclin analogue, the prolonged beneficial effect of which on vascular graft flow rates has been demonstrated previously. Electron microscopy and image analysis of calf capillaries confirmed that critical limb ischemia patients had endothelial cell swelling before bypass, and that cross-clamp ischaemia caused further endothelial swelling in the placebo group. Samples from muscles proximal to the site of the bypass showed similar changes, indicating that systemic capillary damage occurs in muscle remote from the area of ischaemia. Iloprost treatment prevented endothelial swelling and increased the mean capillary lumen cross-sectional area. Iloprost, therefore, has a potentially beneficial effect on capillary function by limiting reperfusion injury during femorodistal bypass.

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Claudication induces systemic capillary endothelial swelling

Cited by 30 publications

References 9 publications

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Blood Oxygenation Level–Dependent Magnetic Resonance Imaging of the Skeletal Muscle in Patients With Peripheral Arterial Occlusive Disease

Effect of Muscle Ischaemia and Iloprost during Femorodistal Reconstruction on Capillary Endothelial Swelling

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