Ulf Samuelson

Acupuncture and sensory neuropeptides increase cutaneous blood flow in rats

The effect on blood flow of electro-acupuncture (EA) injection of substance P (SP) and calcitonin gene-related peptide (CGRP) was studied in musculocutaneous flaps in the rat, using laser Doppler flowmetry. The circulatory border was estimated before and after treatment. It was shown that treatment with EA increased the blood flow moving the circulatory border distally 66% after a treatment. Injection of NaCl into the dorsal central vein of the flap resulted in no increase in blood flow whereas SP 10(-9) M and CGRP 10(-9) M increased the blood flow so that the circulatory border moved distally 31% and 49%, respectively. It is suggested that the effect of EA on blood flow is similar to the effect achieved by injecting CGRP and SP.

Calcitonin gene-related peptide inhibits spontaneous contractions in human uterus and fallopian tube

The localization and effects of calcitonin gene-related peptide (CGRP) in the human uterus and fallopian tube were investigated. CGRP-immunoreactive nerve fibers were found in the muscular layers, around blood vessels and close to the epithelium. The oviduct and uterine cervix were more densely innervated than the corpus of the uterus. Substance P (SP)-like immunoreactivity was found in nerves with an overlapping distribution to that of CGRP-positive fibers. CGRP (2 X 10(-10) to 10(-7) M) dose-dependently and reversibly inhibited spontaneous contractions of uterine and oviductal strips, as well as SP-induced contractions in the oviduct. A role for CGRP-containing nerve fibers in regulation of motor activity in human female reproductive organs is suggested.

Comparison of vascular effects of ropivacaine and lidocaine on isolated rings of human arteries.

Ropivacaine is a new local anaesthetic agent. Previous animal studies have indicated that vasoconstrictor effects are elicited by ropivacaine in vitro and subcutaneously and that it produces blanching of the skin if injected subcutaneously in humans.

Action and localization of neuropeptide Y in the human fallopian tube

Using indirect immunohistochemistry, neuropeptide Y-like immunoreactivity was found in nerve fibers around blood vessels and in the muscle layers of the human fallopian tube. Apart from a network of immunoreactive nerve fibers in connection with the luminary epithelium of the isthmus, the distribution resembled that of adrenergic, tyroxine hydroxylase immunoreactive, nerve fibers. Neuropeptide Y was found to have a dose-dependent inhibitory action on the adrenergic contractile response to field stimulation in the external longitudinal muscle layer of the isthmus. Furthermore, neuropeptide Y inhibited [3H]noradrenaline release from isthmic preparations during field stimulation, suggesting a prejunctional inhibitory action on adrenergic neurotransmission.

Dexamethasone increases survival and attenuates induction of inducible nitric oxide synthase in experimental skin flaps.

The molecule nitric oxide synthesized by the enzyme nitric oxide synthase (NOS) has been shown to be of major physiological and pathophysiological importance in the body. During ischemia and reperfusion, induction of free ionic calcium (Ca2+)-independent inducible NOS (iNOS) is thought to result in an overproduction of NO, leading to tissue damage. The glucocorticoid dexamethasone is known to inhibit the induction of iNOS, and the aim of the current study was to determine the effect of dexamethasone on viability and NOS activity in an ischemic flap model on the dorsum of the rat. Vehicle (N = 20) or dexamethasone (N = 20) was administered 3 hours prior to operation. The surviving area was measured and the flaps were removed after 24 hours for 10 rats in each group and after 48 hours for the remaining 10 rats in each group. Treatment with dexamethasone resulted in an improved flap viability at both 24 hours (p < 0.001) and 48 hours (p < 0.01), and a reduced induction of Ca2+-independent NOS activity in the proximal part of the flaps at 24 hours (p < 0.001). In the current study the authors show that dexamethasone attenuates the induction of Ca2+-independent NOS and increases survival in experimental skin flaps.

Calcitonin gene-related peptide increases microcirculation after mechanically induced ischemia in an experimental island flap.

Vasoconstriction, as a result of mechanical manipulation of blood vessels during microsurgery, may produce a decrease in blood supply and endanger flap viability. A study was undertaken to determine the effects of the topical vasodilator calcitonin generelated peptide on the microcirculation of flaps after mechanically induced ischemia. A neurovascular island flap based on the superficial epigastric vessels was raised in 42 rats. Blood cell flux in the flap was recorded continuously with a laser Doppler flux meter. The feeding artery was pinched to induce vasospasm, and different concentrations of calcitonin gene-related peptide (10−7, 10−8, 10−9, 10−10 mol) or a control of sodium chloride 0.9% was applied topically to relieve the ischemia. Results showed that calcitonin gene-related peptide at a concentration of 10−7 mol significantly shortened the time to reach 50% of the original blood cell flux values (270 ± 123 seconds) and significantly increased the number of flaps in which the blood cell flux values were restored to prestress levels within 30 minutes. The data support the conclusion that, in this model, topical calcitonin gene-related peptide at the concentration of 10−7 mol was effective in promoting recovery of the microcirculation after mechanically induced ischemia, without the adverse effects associated with other commonly used vasodilators.

Increased Skin Flap Survival and Arterial Dilation by Calcitonin Gene-Related Peptide: A Study in the Pig

Calcitonin gene-related peptide (CGRP), a recently discovered neuropeptide, is a potent vasodilator and increases blood flow in many vascular beds. The effect of CGRP treatment was investigated in critical pig pedicle and island flaps. Prior to pharmacological treatment the peroperative circulation border was estimated with fluorescein. Intradermal or intraarterial flap treatment with CGRP was given. Control flaps were untreated or injected with saline. Increased or decreased survival was calculated as the difference between the peroperative fluorescein penetration border and the survival border one week after surgery. CGRP treatment significantly increased the survival of both random pedicle and island flaps. CGRP doses as low as 3 ml x 10(-14) M (equal to 0.03 fmoles) increased the survival of random pedicle flaps. In 4 untreated pigs the deep circumflex iliac arteries were excised and artery ring preparations were studied in vitro. A dose-dependent relaxation of artery rings was noted between 10(-9) M and 10(-7) M CGRP.

Endothelin reduces blood flow in experimental skin flaps

An island buttock flap based on the deep circumflex iliac artery and vein was raised in four pigs. Cutaneous laser Doppler blood flow (LDF) and total venous outflow (VO) from the flaps were measured. Intra-arterial infusion of endothelin-1 (0.3-2.5 nmol) through a branch of the deep circumflex iliac artery induced a pronounced and long lasting decrease in both LDF and VO. The maximal mean reductions being 95.3% and 73%, respectively, were seen within 5 minutes of the infusion. Intra-arterial infusions of endothelin in the circumflex iliac artery on the contralateral side caused a considerable reduction in intact skin LDF. Endothelin has potent vasoconstricting properties and its possible release and effect must be considered in reconstructive surgery.

Injection of Stabilized Hyaluronic Acid-Based Gel of Non-Animal Origin for the Correction of Nasolabial Folds: Comparison with and without Lidocaine

BACKGROUND The use of injectable hyaluronic acid–based gel of non‐animal origin, manufactured using the patented NASHA technology, is well established in aesthetic facial procedures. OBJECTIVE To compare injection pain, dermal filler efficacy, and safety of NASHA‐based gel with or without 0.3% lidocaine hydrochloride when administered to the nasolabial fold (NLF). METHODS Forty‐three subjects seeking correction of NLFs, with moderate or severe wrinkle severity, were recruited for this split‐face, double‐blind, comparative study. NASHA‐based gel, with or without lidocaine hydrochloride, was injected into the deep layer of the dermis and/or subcutis, of the NLF. Pain, efficacy, and safety assessments included a treatment preference question, a 100‐mm visual analogue scale for pain, the Wrinkle Severity Rating Scale, and adverse event reporting. RESULTS Ninety percent of subjects (lower 95% confidence limit=76%) rated injection of NASHA‐based gel with lidocaine as less painful than NASHA‐based gel alone. Subjects and physicians reported no significant differences in dermal filler efficacy between the two treatments during the 12‐month follow‐up period. The safety profile was similar for both products. CONCLUSION NASHA‐based gel with lidocaine provides a more comfortable treatment experience than NASHA‐based gel alone, with equivalent efficacy and safety observed after 12 months of follow‐up. Q‐Med provided the Restylane Perlane with and without lidocaine and equipment used in this study. Ken Sutor, Fishawack Communications, provided assistance in writing this manuscript.

Intradermal lignocaine injections increase blood cell flux but not flap survival in rats.

In four groups of six rats a random dorsal flap was raised, and 5, 20, or 200 mg/ml lignocaine or 0.9% sodium chloride, were injected intradermally. Cutaneous laser Doppler blood cell flux was measured at 12 time points over 130 minutes. In six other groups 5, 20, 100, 200, or 400 mg/ml lignocaine concentrations, or sodium chloride were tested. Blood cell flux was measured at the time that the flap was raised and 30 minutes after the injections. The area of the flap that survived was measured on day 10. Raising of the flaps resulted in a significant reduction in blood cell flux, which was followed by a significant increase at 10 minutes (p < 0.05) after the injections with all lignocaine concentrations tested. Injections of 5, 20 and 100 mg/ml lignocaine elicited a significant increase (p < 0.05) in blood cell flux compared with baseline values. There was no reduction in blood cell flux values at any concentration of lignocaine tested. Compared with sodium chloride, injections of lignocaine had no significant effect on flap survival. We conclude that, despite an increase in blood cell flux, lignocaine had no effect on flap survival in this model.