Altered small artery morphology and reactivity in critical limb ischaemia

1999 ◽  
Vol 96 (2) ◽  
pp. 155-163 ◽  
Author(s):  
C. HILLIER ◽  
R. D. SAYERS ◽  
P. A. C. WATT ◽  
R. NAYLOR ◽  
P. R. F. BELL ◽  
...  

Although the pathophysiology of critical limb ischaemia is poorly understood, there is evidence that the condition of the small arteries may determine the outcome of revascularization procedures. This study was designed to investigate the effects of critical limb ischaemia on the structure and function of the small arteries in the leg. Small arteries (< 500 μm) from proximal (non-ischaemic) and distal (ischaemic) sites were obtained from patients undergoing bypass surgery for critical limb ischaemia and mounted in a myograph. Reactivity and morphological measurements were carried out and compared with controls. Control vessels from the thigh and calf showed no difference in media to lumen ratio. However, a comparison of ischaemic and non-ischaemic vessels from the patients with critical limb ischaemia showed significant thinning of the ischaemic vessel wall. Contraction studies using noradrenaline and angiotensin II revealed a significant decrease in the response of ischaemic vessels compared with the non-ischaemic vessels from the same patient. Moreover, these differences in reactivity were still apparent after the responses were corrected for wall thickness. Endothelial function assessed using the endothelium-dependent agonists acetylcholine and bradykinin showed a significantly impaired relaxation response to acetylcholine but not to bradykinin in the ischaemic vessels, and acetylcholine-induced relaxation was not improved after incubation with indomethacin. There was no change in the response to the endothelium-independent cAMP-mediated vasodilator iloprost but a significant impairment to sodium nitroprusside which acts via cGMP. These results suggest that small arteries in critical limb ischaemia are altered in both structure and function, with vessel wall thinning and impaired responses to acetylcholine and sodium nitroprusside.

1997 ◽  
Vol 84 (10) ◽  
pp. 1425-1429 ◽  
Author(s):  
M. M. I. Yassin ◽  
A. A. B. Barros D'Sa ◽  
T. G. Parks ◽  
M. D. McCaigue ◽  
P. Leggett ◽  
...  

1997 ◽  
Vol 84 (10) ◽  
pp. 1425-1429 ◽  
Author(s):  
M. M. I. Yassin ◽  
A. A. B. Barros D'Sa ◽  
T. G. Parks ◽  
M. D. McCaigue ◽  
P. Leggett ◽  
...  

2003 ◽  
Vol 105 (6) ◽  
pp. 683-689 ◽  
Author(s):  
P. COATS

In critical limb ischaemia (CLI), the ability to regulate regional blood flow in the diseased portion of the leg would appear to be severely compromised. Considering this, pressure-dependent myogenic and mechanical properties of resistance arterioles isolated from control subjects and from patients with CLI were studied. Using confocal microscopy and pressure myography, subcutaneous resistance arteriole structure and function were compared between subcutaneous arterioles isolated from healthy volunteers [control subcutaneous (CS)] and non-diseased proximal subcutaneous (PS; internal control) and distal subcutaneous (DS) arterioles from the diseased ischaemic part of the limb from patients with CLI. Significant wall atrophy was observed in DS arterioles compared with PS and CS arterioles. Passive pressure-dependent mechanical properties were significantly altered in the diseased arterioles compared with PS and CS arterioles. Active pressure-dependent myogenic tone was completely absent in DS arterioles. The atrophic structural remodelling in DS arterioles were correlated with the changes in vascular mechanics, but not with the ability of these arterioles to contract in response to chemical stimuli. However, active pressure-dependent myogenic tone was absent in the DS arterioles. The combination of altered pressure-dependent passive mechanical and active myogenic tone goes some way in explaining CLI sequelae and poor outcome following surgical revascularization experienced by these patients.


1998 ◽  
Vol 274 (5) ◽  
pp. C1298-C1305 ◽  
Author(s):  
Nicola Stephens ◽  
Mark J. Drinkhill ◽  
Alistair S. Hall ◽  
Stephen G. Ball ◽  
Anthony M. Heagerty

The structure and function of subcutaneous small arteries from patients with mild heart failure ( n = 27) 6–43 mo after myocardial infarction were compared with vessels from healthy control subjects ( n = 10). Patients were randomized to treatment with placebo or the angiotensin-converting enzyme inhibitor ramipril starting 3–10 days after myocardial infarction. Dissected arterial vessels were mounted on a wire myograph for measurement of morphology and isometric tension. Morphology was not different in arteries from the three groups. Responses to norepinephrine, angiotensin II, and electrical field stimulation were similar in arteries from placebo-treated patients with mild heart failure and control subjects. Similarly, endothelium-dependent and -independent relaxation was normal in arteries from patients with mild heart failure. Ramipril therapy was associated with functional alterations: vasoconstrictor responses to norepinephrine and angiotensin II were significantly enhanced compared with placebo ( P < 0.001). These data suggest that vascular structure and function are not different in vitro in subcutaneous arteries from placebo-treated patients with mild heart failure. Angiotensin-converting enzyme inhibitor therapy is associated with enhanced vasoconstriction to norepinephrine and angiotensin II, which may reflect upregulation of receptor-mediated events.


1991 ◽  
Vol 1 (7) ◽  
pp. 931-948
Author(s):  
P A Marsden ◽  
M S Goligorsky ◽  
B M Brenner

Vascular endothelium is now appreciated to modulate vessel wall structure and function in health and disease. Strategically located between the intravascular space and vessel wall proper, the endothelium has a broad capacity to modify the functional state of adjacent or trafficking cells. Furthermore, recent findings indicate that the endothelium is an interactive tissue capable of responding to numerous mechanical, chemical, and cellular stimuli. The focus of this review will be a discussion of endothelial cell biology in relation to vascular structure and function, with particular emphasis on endothelial modulation of vasomotor tone. It is evident that endothelial cells contribute to the local control of vascular tone by releasing potent vasodilatory mediators, such as endothelium-derived relaxing factor, and vasoconstrictor mediators such as endothelin-1. The endothelium also serves to modify blood-borne signals to which vascular tissues respond. The kidney shares, directly and indirectly, in these events, making this emerging new area a focus of major interest for nephrologists.


1995 ◽  
Vol 13 (5) ◽  
pp. 535-541 ◽  
Author(s):  
Stuart J. Bund ◽  
Alex A. Oldham ◽  
Christopher P. Allott ◽  
Bernard E. Loveday ◽  
Anthony M. Heagerty

Author(s):  
Louise CD Konijn ◽  
Richard AP Takx ◽  
Willem PThM Mali ◽  
Hugo TC Veger ◽  
Hendrik van Overhagen

Objectives The most severe type of peripheral arterial disease (PAD) is critical limb ischaemia (CLI). In CLI, calcification of the vessel wall plays an important role in symptoms, amputation rate and mortality. However, calcified arteries are also found in asymptomatic persons (non-PAD patients). We investigated whether the calcification pattern in CLI patients and non- PAD patients are different and could possibly explain the symptoms in CLI patients. Materials and Methods 130 CLI and 204 non-PAD patients underwent a CT of the lower extremities. This resulted in 118 CLI patients (mean age 72&plusmn;12, 70.3% male) that were age-matched with 118 non-PAD patients (mean age 71&plusmn;11, 51.7% male). The characteristics severity, annularity, thickness and continuity were assessed in the femoral and crural arteries and analysed by binary multiple logistic regression. Results Nearly all CLI patients have calcifications and these are equally frequent in the femoropopliteal (98.3%) and crural arteries (97.5%), while the non-PAD patients had in just 67% any calcifications with more calcifications in the femoropopliteal (70.3%) than in the crural arteries (55.9%, p&lt;0.005). The crural arteries of the CLI patients had significantly more complete annular calcifications (OR 2.92, p=0.001.) while in the non-PAD patients dot-like calcifications dominated. In CLI patients, the femoropopliteal arteries had more severe, irregular / patchy and thick calcifications (OR 2.40, 3.27, 1.81, p&le;0.05, respectively) while in non-PAD patients, thin continuous calcifications prevailed. Conclusions Compared with non-PAD patients CLI patients are more frequently and extensively calcified. Annular calcifications were found in the crural arteries of CLI patients while dot-like calcifications were mostly present in the non-PAD patients. These different patterns of calcifications in CLI point at different etiology and can have prognostic and eventually therapeutic consequences.


Author(s):  
Wen Tang ◽  
Zhaoyou Meng ◽  
Ning Li ◽  
Yiyan Liu ◽  
Li Li ◽  
...  

The study of the gut microbiota-brain axis has become an intriguing field, attracting attention from both gastroenterologists and neurobiologists. The hippocampus is the center of learning and memory, and plays a pivotal role in neurodegenerative diseases, such as Alzheimer’s disease (AD). Previous studies using diet administration, antibiotics, probiotics, prebiotics, germ-free mice, and fecal analysis of normal and specific pathogen-free animals have shown that the structure and function of the hippocampus are affected by the gut microbiota. Furthermore, hippocampal pathologies in AD are positively correlated with changes in specific microbiota. Genomic and neurochemical analyses revealed significant alterations in genes and amino acids in the hippocampus of AD subjects following a remarkable shift in the gut microbiota. In a recent study, when young animals were transplanted with fecal microbiota derived from AD patients, the recipients showed significant impairment of cognitive behaviors, AD pathologies, and changes in neuronal plasticity and cytokines. Other studies have demonstrated the side effects of antibiotic administration along with the beneficial effects of probiotics, prebiotics, and specific diets on the composition of the gut microbiota and hippocampal functions, but these have been mostly preliminary with unclear mechanisms. Since some specific gut bacteria are positively or negatively correlated to the structure and function of the hippocampus, it is expected that specific gut bacteria administration and other microbiota-based interventions could be potentially applied to prevent or treat hippocampus-based memory impairment and neuropsychiatric disorders such as AD.


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