Skin Microcirculation in Patients with Type I Diabetes with and without Neuropathy after Neurovascular Stimulation

Forst, Thomas; Pfützner, Andreas; Kunt, T.; Pohlmann, T.; Schenk, Ulrike; Bauersachs, Rupert; Küstner, Eva; Beyer, J.

doi:10.1042/cs0940255

Cited by 37 publications

(19 citation statements)

References 18 publications

(12 reference statements)

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“…The iontophoresis of deionized water in the same polarity with that of acetylcholine (i.e., with an anodal constant current) has been previously shown to lead to a small nonspecific galvanic effect (20,21). In contrast, iontophoresis with a cathodal current, as used for the iontophoresis of sodium nitroprusside, has been reported in one study to result in a significant nonspecific vasodilatory response (22).…”

Section: Foot Levelmentioning

confidence: 86%

“…However, the magnitude of the contribution of each of these two factors to the total vasodilation has not been adequately studied, and the currently available data are conflicting. Thus, although some studies have suggested a considerably higher contribution of the neurovascular response, the techniques used did not allow the precise quantification of this contribution (8,21). On the other hand, another study has shown that local sensory inhibition by topical application of lignocaine and prilocaine did not have an effect on the total vasodilatory response to the iontophoresis of acetylcholine (22).…”

Section: Foot Levelmentioning

confidence: 98%

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Contribution of Nerve-Axon Reflex-Related Vasodilation to the Total Skin Vasodilation in Diabetic Patients With and Without Neuropathy

et al. 2001

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OBJECTIVE -To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects.RESEARCH DESIGN AND METHODS -The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water.RESULTS -The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P Ͻ 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerveaxon-related vasodilation was observed during the iontophoresis of sodium nitroprusside, which does not specifically stimulate the C nociceptive fibers.CONCLUSIONS -Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways.

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Section: Foot Levelmentioning

confidence: 86%

Section: Foot Levelmentioning

confidence: 98%

Contribution of Nerve-Axon Reflex-Related Vasodilation to the Total Skin Vasodilation in Diabetic Patients With and Without Neuropathy

et al. 2001

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“…This possibility was suggested by Forst et al (22), who proposed that the effect of intracutanous ACh on CuBF is mediated mainly by the axon reflex. The situation is more complex, however, as there is evidence that the iontophoretic current alone may also induce an axon reflex (9).…”

mentioning

confidence: 88%

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Berghoff

Kathpal

Kilo

et al. 2002

Journal of Applied Physiology

109

118

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nisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation. J Appl Physiol 92: 780-788, 2002; 10.1152/japplphysiol.01167.2000.-The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex. endothelium; prostaglandin; nitric oxide; axon reflex; acetylcholine CUTANEOUS BLOOD FLOW (CuBF) is regulated by endothelial, neural, and humoral factors. The interaction between these mechanisms of blood flow control is poorly defined. Recent studies of CuBF have used the technique of laser-Doppler flowmetry in combination with the iontophoretic application of charged vasoactive agents. Acetylcholine (ACh) has been used to induce endothelium-mediated blood flow, and the direct nitric oxide (NO) donor sodium nitroprusside has been used to provoke non-endothelium-mediated blood flow. Despite the widespread use of ACh-evoked vasodilation in studies investigating vascular physiology and pathophysiology, the mechanisms responsible for its effect, particularly in the cutaneous microcirculation, are unresolved. This question has important implications. If prostaglandins do play a major role in endotheliummediated vasodilation, some effects of acetylsalicylic acid (ASA) therapy, which is extensively used for its prophylactic antiplatelet effect in patients with cardiovascular and cerebrovascular disease (17, 27), may be counterproductive. Furthermore, if prostaglandins play a major role in the C-fiber-mediated axon reflex, reduction of this reflex by cyclooxygenase inhibition may attenuate the ability to mount a neurogenic inflammatory response (4, 48). Attenuation of this important protective reflex in patients with peripheral neuropathy impairs wound healing and increases susceptibility to infection, thereby leading to cutaneous ulceration, gangrene, and ultimately amputation (3,21).Factors released by the endothelium in response to ACh include NO, vasoactive prostanoi...

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“…Before the start of the investigation, the patients rested in a supine position for at least 15 min and the mean LDF was recorded for 3 min at a probe temperature of 37°C and 44°C. The mean individual coefficient of variation of microvascular blood flow measurement using this method is 20% (8,9).…”

Section: Laser Doppler Fluxmetrymentioning

confidence: 98%

Effect of Insulin Glulisine on Microvascular Blood Flow and Endothelial Function in the Postprandial State

et al. 2008

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OBJECTIVE -To investigate the effect of insulin glulisine on postprandial microvascular blood flow in type 2 diabetes.RESEARCH DESIGN AND METHODS -A total of 15 patients with type 2 diabetes received insulin glulisine or human insulin before a liquid meal test. Thereafter, skin microvascular blood flow was measured by laser Doppler fluxmetry and blood samples were taken for measurement of plasma levels of glucose, insulin, intact proinsulin, asymmetric dimethylarginine, nitrotyrosine, interleukin-18, matrix metalloproteinase-9, oxidized LDL, and free fatty acids.RESULTS -Insulin glulisine injections resulted in higher postprandial insulin levels (means Ϯ SEM area under the curve [AUC] 0 -120 51.0 Ϯ 6.8 vs. 38.2 Ϯ 5.4 mU/l; P ϭ 0.004), while plasma glucose (AUC 0 -240 158 Ϯ 9 vs. 180 Ϯ 9 mg/dl; P Ͻ 0.05) and intact proinsulin (AUC 0 -240 26.2 Ϯ 3.5 vs. 31.2 Ϯ 4.3 pmol/l; P ϭ 0.002) were lower. Microvascular blood flow increased after insulin glulisine injection (27.9 Ϯ 3.1 to 51.7 Ϯ 9.9 arbitrary units [AU]; P Ͻ 0.05), while only a minor increase was found during human insulin (27.9 Ϯ 3.1 to 34.4 Ϯ 7.8 AU; not significant). Asymmetric dimethylarginine and nitrotyrosine levels were reduced after insulin glulisine (P Ͻ 0.05).CONCLUSIONS -Insulin glulisine is superior to human insulin in restoring postprandial metabolic and microvascular physiology. Diabetes Care 31:1021-1025, 2008S everal epidemiological studies have demonstrated an association between glucose spikes and the development of vascular complications in patients with type 2 diabetes. Postprandial generation of oxidative stress and impaired endothelial function are major contributors in the development of early vascular damage and atherosclerosis. Recent studies have shown that microvascular blood flow increases after a meal in gut, skin, heart, and adipose tissues (1-5). Postprandial regulation of microvascular blood flow is a complex process inversely affected by postprandial glucose and insulin excursions (2,6,7).Diminished prandial insulin secretion and an increase in postprandial plasma glucose excursions with increased postprandial oxidative stress and impaired endothelial function are early features of type 2 diabetes. Insulin glulisine attenuates the postprandial increase in plasma levels of intact proinsulin compared with regular human insulin, which may lead to a corresponding reduction in cardiovascular risk and ␤-cell protection. Therefore, the pharmacokinetics of prandial insulin formulations may be important not only in controlling postprandial glucose excursions, but also in the maintenance of normal endothelial function and microvascular blood flow. The aim of this study was to compare the effect of insulin glulisine with regular human insulin in terms of postprandial microvascular blood flow and several laboratory markers of endothelial function and oxidative stress in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS -This investigation wasa single-center, open-label, randomized, two-way crossover study of patients with type 2 ...

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Skin Microcirculation in Patients with Type I Diabetes with and without Neuropathy after Neurovascular Stimulation

Cited by 37 publications

References 18 publications

Contribution of Nerve-Axon Reflex-Related Vasodilation to the Total Skin Vasodilation in Diabetic Patients With and Without Neuropathy

Contribution of Nerve-Axon Reflex-Related Vasodilation to the Total Skin Vasodilation in Diabetic Patients With and Without Neuropathy

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Effect of Insulin Glulisine on Microvascular Blood Flow and Endothelial Function in the Postprandial State

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