Treatment of end-stage peripheral artery disease by neuromodulation.

BACKGROUND: Neuromodulation is a therapeutic option to improve limb salvage in end-stage peripheral arterial disease (PAD), but there is no consensus on its indication for spinal cord stimulation (SCS) in PAD patients. OBJECTIVE: The aim of this study was to present the outcome of end-stage PAD patients treated with SCS. METHODS: This study is a retrospective analysis based on a local prospective registry. Neuromodulation was performed if there was: 1) no revascularisation option, 2) no septicemia, 3) and Rutherford stage 4-6. The primary endpoint of the study was limb salvage. Secondary endpoints were reduction in pain or simply pain reduction pain (assessed using a visual anlog scale/VAS) and improvement in walking distance. RESULTS: Limb salvage was reached in 30/34 patients (88%). Patients reported a significant reduction in pain on the 10-point VAS scale from baseline (median = 7.5, IQR = 7-8) to follow-up at 2 years (median = 0, IQR 0-2.75), p < 0.001. Walking distance also improved from preoperative (median = 50 m, IQR = 20-50 m) to follow-up at 2 years (median = 150 m, IQR 50-272 m), p < 0.001. RESULTS: SCS implantation in patients with end-stage PAD can enable limb salvage in a high percentage of cases and increase mobility due to pain reduction. The role of microcirculation in these improvements needs to be investigated in further studies.

Cerebral arteriogenesis is enhanced by pharmacological as well as fluid-shear-stress activation of the Trpv4 calcium channel.

OBJECTIVES: This study aimed to determine the importance of the shear-stress-sensitive calcium channels Trpc1, Trpm7, Trpp2, Trpv2 (transient receptor potential cation channel, subfamily V, member 2) and Trpv4 for cerebral arteriogenesis. The expression profiles were analysed, comparing the stimulation of collateral growth by target-specific drugs to that achieved by maximum increased fluid shear stress (FSS). DESIGN: A prospective, controlled study wherein rats were subjected to bilateral carotid artery ligature (BCL), or BCL + arteriovenous fistula, or BCL + drug application. METHODS: Messenger RNA (mRNA) abundance and protein expression were determined in FSS-stimulated cerebral collaterals by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Drugs were applied via osmotic mini pumps and arteriogenesis was evaluated by post-mortem angiograms and Ki67 immunostaining. RESULTS: Trpv4 was the only mechanosensitive Trp channel showing significantly increased mRNA abundance and protein expression after FSS stimulation. Activation of Trpv4 by 4α-phorbol-12,13-didecanoate caused significantly enhanced collateral growth (length: 4.43 ± 0.20 mm and diameter: 282.6 ± 8.1 µm) compared with control (length: 3.80 ± 0.06 mm and diameter: 237.3 ± 5.3 µm). Drug application stimulated arteriogenesis to almost the same extent as did maximum FSS stimulation (length: 4.61 ± 0.07 mm and diameter: 327.4 ± 12.6 µm). CONCLUSIONS: Trpv4 showed significantly increased expression in FSS-stimulated cerebral collaterals. Pharmacological Trpv4 activation enhanced cerebral arteriogenesis, pinpointing Trpv4 as a possible candidate for the development of new therapeutic concepts.

Exercise linked to transient increase in expression and activity of cation channels in newly formed hind-limb collaterals.

OBJECTIVE: This study aimed to compare arteriogenesis after femoral artery occlusion as influenced by exercise or arteriovenous shunt and follow changes in collateral transient receptor potential cation channel, subfamily V, member 4 (Trpv4). DESIGN: A prospective, controlled study wherein rats were subjected to femoral artery ligation (FAL), or FAL+arteriovenous shunt. Collateral Trpv4 was determined 0.5 and 6h post exercise. METHODS: Rats were subjected to exercise for 15 min, twice daily. The number and diameter of collaterals were assessed after 7 days. Collateral Trpv4 expression was quantified by reverse transcription-polymerase chain reaction. RESULTS: Collateral number and diameter per limb were significantly higher in the shunt group (number: 16.0+/-2.4 and diameter: 216.0+/-34 microm) compared to the ligature (number: 9.4+/-2 and diameter: 144+/-21 microm) and exercise groups (number: 9.9+/-2.5 and diameter: 151+/-15 microm). Trpv4 expression in collaterals harvested 0.5h post exercise was not significantly different from expression in shunted rats. It was significantly lower in collaterals harvested 6h post exercise (comparable to that in ligated rats). CONCLUSION: Collateral formation was greater in the shunt group than in the exercise group. Exercise-induced Trpv4 up-regulation, not significantly different from that achieved with shunt, returned to control values when evaluated 6h post exercise. More frequent exercise to chronically increase fluid shear stress, as with a shunt model, may be required for sufficient arteriogenesis to compensate for peripheral occlusion.

Ultrasound diagnostics of renal artery stenosis: Stenosis criteria, CEUS and recurrent in-stent stenosis.

BACKGROUND AND PURPOSE: As a non-invasive, side effect-free and cost-effective method, ultrasonography represents the method of choice for the diagnosis of renal artery stenosis. Four different criteria in total, including two direct criteria in peak systolic velocity (PSV) and renal aortic ratio (RAR) and two indirect criteria in resistance index (RI) and acceleration time (AT) for the measurement of relevant renal artery stenosis are described, each demonstrating highly variable accuracy in studies. Furthermore, there is controversy over the degree beyond which stenosis becomes therapeutically relevant and which ultrasound PSV is diagnostically relevant in terms of stenosis grading. MATERIAL AND METHODS: This article gives a critical review based on a selective literature search on measurement methodology and the validity of ultrasound in renal artery stenosis. A critical evaluation of methods and a presentation of measurement principles to establish the most precise measurement method possible compared with the gold standard angiography, as well as an evaluation of the importance of computed tomography angiography (CTA) and magnetic resonance angiography (MRA). RESULTS AND CONCLUSIONS: The PSV provides high sensitivity and specificity as a direct measurement method in stenosis detection and grading. Most studies found sensitivities and specificities of 85-90 % for > 50 % stenosis at a PSV > 180-200 cm/s in ROC curve analysis. Other methods, such as the ratio of the PSV in the aorta to the PSV in the renal artery (RAR) or indirect criteria, such as side to side differences in RI (dRI) or AT can be additionally used to improve accuracy. Contrast-enhanced ultrasound improves accuracy by means of echo contrast enhancement. Although in the past only high-grade stenosis was considered relevant for treatment, a drop in pressure of > 20 mmHg in > 50 % stenosis (PSV 180 cm/s) is classified as relevant for increased renin secretion. Stenosis in fibromuscular dysplasia can be reliably graded according to the continuity equation. Although the available studies on the grading of in-stent restenosis are the subject of controversy, there is a tendency to assume higher cut-off values for PSV and RAR. Whilst MRA and CTA demonstrate an accuracy of > 90 %, this is at the cost of possible side effects for patients, particularly in the case of pre-existing renal parenchymal damage. ADDITIONAL ONLINE MATERIAL: This article includes two additional video sequences on visualizing renal artery stenosis. This supplemental material can be found under: dx.doi.org/10.1007/s00772-015-0060-3.

Inferior Mesenteric Artery Side Branch for Selected Patients with Endovascular Aortic Aneurysm Repair.

OBJECTIVE/BACKGROUND: To report on our experience of the treatment of aortic aneurysms by custom-made, branched stent-grafts with an additional inferior mesenteric artery (IMA) side branch to preserve IMA perfusion in patients at risk for colon ischemia. METHODS: Three male patients (mean age 60 years) with a thoracoabdominal, pararenal, and infrarenal aortic aneurysm (AA), respectively, were treated by endovascular aneurysm exclusion using custom-made, branched stent-grafts with a side branch to the IMA for prevention of colon ischemia. Indications for selective IMA side branch perfusion were occlusions or high-grade stenosis of the visceral or hypogastric arteries. RESULTS: No colon ischemia and no neurological deficit were observed. All three IMA side branches were perfused and patent, as documented by computed tomography scan and duplex ultrasound postoperatively and after 12 months. Patency after 24 months was documented as 2/3. CONCLUSION: Custom-made, branched stent-grafts are an endovascular option to preserve the IMA perfusion in selected, electively treated patients with an increased risk for insufficient colon perfusion due to stenosis or occlusions of visceral or hypogastric arteries.

Ultrasound diagnostics of the abdominal aorta: English version.

BACKGROUND AND OBJECTIVES: The ideal method for screening investigations is one which is as free as possible from side effects, is easily learnt, and can therefore be broadly used to detect abdominal aortic aneurysms (AAA) with a high degree of certainty. Although ultrasonography fulfils these criteria, the measurement method is not standardized. Different measurement methods are used in ultrasonography as well as in computed tomography (CT) studies and the measurement method is actually described sufficiently in only 57 % of cases. METHODS: This article provides a critical review of the current literature on measurement methods and the validity of ultrasonography for the determination of aortic diameter, particularly in AAA, and presents the measurement principles for making measurements as precisely as possible. RESULTS AND CONCLUSION: The most precise determination of aortic diameter is carried out by electrocardiogram (ECG) gating according to the leading-edge method with orthogonal slicing. Within the framework of screening investigations, sufficient measurement precision can be achieved by adherence to orthogonal slicing. Using these standardized measurement methods, ultrasonography shows valid and reproducible results even compared with CT and is the method of choice in screening investigations for AAA.

Fates of genetically engineered haematopoietic and mesenchymal stem cell grafts in normal and injured rat hearts.

There is an ongoing debate on the potential of adult stem cells as adjuvant therapy for patients with heart disease. The aim of our study was to evaluate the use of bone marrow (BM)-derived stem cells for cardiac cell and gene therapy in normal and ischaemia-injured rat hearts. Haematopoietic (HSCs) and mesenchymal stem cells (MSCs) were purified from the BM of adult rats and labelled by: (a) genetic transduction of the green fluorescent protein (GFP) using an oncoretroviral vector; (b) incorporation of the fluorescent dye PKH26 into the cell membrane; and (c) incorporation of bromodeoxyuridine into the chromosomal nucleic acid. Cells were directly injected into the beating heart (normal and shortly after coronary ligation). Retention of HSCs was--irrespective of the ischaemic injury--about 5% on day 3, and < 1% on days 10 and 28. Survival of MSCs was approximately 10-15% on day 3, but also < 5% at the later time points. Vector-mediated GFP expression was rapidly silenced after day 3. There was considerable tissue damage around the injection site. Transplanted cells did not migrate from the injection site. We did not observe phenotypical changes of the transplanted stem cells into cardiac or vascular cells.