A controlled study of the effects of pulsed ultrasound was carried out in conjunction with a standard treatment for healing chronic leg ulcers on 44 patients divided randomly into two groups. All patients received standard treatment (paste impregnated bandage and a self-adhesive elastic bandage) plus placebo-ultrasound or pulsed ultrasound (1:9, 0.5 watt/cm2 at 1 MHz, for 10 min) 3 days a week for 4 weeks, thereafter twice weekly for 4 weeks and once weekly for the following 4 weeks. Percentage healed ulcer area and comparison of percentage healed ulcers were examined after 4, 8 and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the pulsed ultrasound group as compared with the placebo group.

The aim of the present study was to examine the effect of the nitric oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on skin and flap blood flow, NOS activity and flap survival in an ischaemic dorsal flap model in the rat.Fifty-four rats were used in the study. L-NAME or the inactive enantiomere D-NAME was given intravenously either pre-, per- and postoperatively or only postoperatively. Controls received saline treatment. Blood pressure and skin and flap blood flow were monitored. NOS activity was measured in intact skin before and after L-NAME and D-NAME infusion and in flap tissue 48 h postoperatively. Forty-eight hours postoperatively flap survival was determined in all rats.L-NAME treatment caused: (1) a marked attenuation of constitutive Ca2+ dependent NOS activity in intact skin (p < 0.001), (2) an increase in blood pressure (p < 0.05), (3) a decrease in blood flow in intact skin and in skin flaps (p < 0.05), and (4) a decrease in flap survival (p < 0.05). In saline and D-NAME treated animals no change in blood pressure, blood flow or NOS activity in intact skin was noted.In conclusion this study shows that L-NAME attenuates constitutive Ca2+ dependent NOS activity in intact skin, decreases skin and flap blood flow and decreases the survival of skin flaps. These results indicate that constitutive nitric oxide synthase is important for basal blood flow in skin and flap tissue and for the survival of skin flaps. (c) 2006 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The aim of the present study was to detect and quantify nitric oxide synthase (NOS) activity and to investigate morphological changes in the endothelium in two different ischaemic dorsal flap models in the rat, one based cranially and one based caudally. Intact skin from the dorsum was used as control. In both groups flaps were removed at 1, 4, 12, 24 and 72 h after surgery respectively. NOS-activity was measured by the conversion of L-arginine to L-citrulline and endothelial morphology was investigated using transmission electron microscopy. Intact skin showed Ca(2+)-dependent but no Ca(2+)-independent NOS-activity. A time-dependent decrease in Ca(2+)-dependent NOS-activity was seen in the proximal and distal part of the flaps in both flap models and was most pronounced in the distal part. Ca(2+)-independent NOS-activity increased in the proximal and distal part of flaps based cranially and in the proximal part of flaps based caudally. Morphological analysis of the endothelium showed signs of endothelial damage including blebbed membranes, swelling and endothelial loss. These findings show that ischaemia caused by skin-flap surgery leads to endothelial damage and a decrease in Ca(2+)-dependent nitric oxide synthase activity. Furthermore, in the skin-flaps an induction of Ca(2+)-independent nitric oxide synthase (iNOS) activity was noted both in surviving flap tissue and in flap tissue destined to necrose.

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.

Effects of adenosine and adenosine analogues on neuroeffector transmission in separate layers of the guinea-pig uterine smooth muscle during different phases of the oestrus cycle were studied. Adenosine (ADO), N6-[(R)-1-methyl-2-phenylethyl]- adenosine (R-PIA) and 5'-N-ethylcarboxamideadenosine (NECA) enhanced spontaneous contractile activity as well as contractile responses to nerve stimulation or direct muscle stimulation in the longitudinal and circular muscle layers both at the time of ovulation and implantation. The agonist potency order was R-PIA greater than or equal to NECA greater than ADO. Furthermore, in the circular muscle layer inhibitory effects were seen at time of implantation and the agonist potency for this inhibitory effect was NECA greater than R-PIA greater than or equal to ADO. 8-p-sulphophenyltheophylline (8-PSOT) antagonized both the stimulatory and inhibitory effects of the purines and 8-p-sulphophenyltheophylline applied to untreated preparations inhibited nerve-induced contractile activity. NECA inhibited stimulation-induced release of 3H in preparations incubated with [3H]noradrenaline. We suggest that adenosine and its analogues can modulate adrenergic neuroeffector transmission in guinea-pig uterine smooth muscle via action at postjunctional receptors stimulating contractile activity and prejunctional receptors inhibiting transmitter release. In the circular muscle layer postjunctional receptors inhibiting contractile activity were evident at time of implantation. Furthermore, endogenous purines exerting a stimulatory action on the neuroeffector transmission were likely formed during the present experimental conditions.

Acta Physiologica ScandinavicaVolume 141, Issue 2 p. 281-282 Calcitonin gene-related peptide relaxes porcine arteries via one endothelium-dependent and one endothelium-independent mechanism U.E. SAMUELSON, Corresponding Author U.E. SAMUELSON Department of Physiology, Karolinska Institute and Department of Plastic and Reconstructive Surgery, Karolinska Hospital, Stockholm, SwedenDepartment of Physiology, Karolinska Intitutet, S-104 01 Stockholm, Sweden.Search for more papers by this authorJ. JERNBECK, J. JERNBECK Department of Physiology, Karolinska Institute and Department of Plastic and Reconstructive Surgery, Karolinska Hospital, Stockholm, SwedenSearch for more papers by this author U.E. SAMUELSON, Corresponding Author U.E. SAMUELSON Department of Physiology, Karolinska Institute and Department of Plastic and Reconstructive Surgery, Karolinska Hospital, Stockholm, SwedenDepartment of Physiology, Karolinska Intitutet, S-104 01 Stockholm, Sweden.Search for more papers by this authorJ. JERNBECK, J. JERNBECK Department of Physiology, Karolinska Institute and Department of Plastic and Reconstructive Surgery, Karolinska Hospital, Stockholm, SwedenSearch for more papers by this author First published: February 1991 https://doi.org/10.1111/j.1748-1716.1991.tb09079.xCitations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume141, Issue2February 1991Pages 281-282 RelatedInformation

Acta Physiologica ScandinavicaVolume 140, Issue 2 p. 297-298 The effects of L-arginine and NG-monomethyl L-arginine on the inhibitory neurotransmission of the human corpus cavernosum penis N. O. SJÖSTRAND, Corresponding Author N. O. SJÖSTRAND Department of Physiology, Karolinska Institutet, Stockholm, SwedenDepartment of Physiology I, Karolinska Institutet, S-104 01 Stockholm, Sweden.Search for more papers by this authorJ. ELDH, J. ELDH Department of Plastic Surgery, Karolinska Hospital, Stockholm, SwedenSearch for more papers by this authorU. E. SAMUELSON, U. E. SAMUELSON Department of Physiology, Karolinska Institutet, Stockholm, Sweden Department of Plastic Surgery, Karolinska Hospital, Stockholm, SwedenSearch for more papers by this authorS. ALARANTA, S. ALARANTA Division of Pharmacology and Toxicology, Department of Pharmacy, University of Helsinki, FinlandSearch for more papers by this authorE. KLINGE, E. KLINGE Division of Pharmacology and Toxicology, Department of Pharmacy, University of Helsinki, FinlandSearch for more papers by this author N. O. SJÖSTRAND, Corresponding Author N. O. SJÖSTRAND Department of Physiology, Karolinska Institutet, Stockholm, SwedenDepartment of Physiology I, Karolinska Institutet, S-104 01 Stockholm, Sweden.Search for more papers by this authorJ. ELDH, J. ELDH Department of Plastic Surgery, Karolinska Hospital, Stockholm, SwedenSearch for more papers by this authorU. E. SAMUELSON, U. E. SAMUELSON Department of Physiology, Karolinska Institutet, Stockholm, Sweden Department of Plastic Surgery, Karolinska Hospital, Stockholm, SwedenSearch for more papers by this authorS. ALARANTA, S. ALARANTA Division of Pharmacology and Toxicology, Department of Pharmacy, University of Helsinki, FinlandSearch for more papers by this authorE. KLINGE, E. KLINGE Division of Pharmacology and Toxicology, Department of Pharmacy, University of Helsinki, FinlandSearch for more papers by this author First published: October 1990 https://doi.org/10.1111/j.1748-1716.1990.tb09002.xCitations: 18AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES Gibson, A., Mirzazadeh, S., Hobbs, A.J. & Moore, P.K. 1990. L-NG-monomethyl arginine and L-NG- nitro arginine inhibit non-adrenergic, non-cholinergic relaxation of the mouse anococcpgeus muscle. Br J Pharmacol 99, 602–606. Gillespie, J.S. & Sheng, H. 1990. The effects of pyrogallol and hydroquinone on the response to NANC nerve stimulation in the rat anococcpgeus and the bovine retractor penis muscles. Br J Pharmarol 99, 194–196. Gillespie, J.S. & Xiaorong, L. 1989. The effect of arginine and L-N monomethyl arginine on the response of the bovine retractor penis to stimulation of its NANC nerves. Br J Pharmarol 97, 45–3P. Gillespie, J.S., Liu, X. & Martin, IT. 1989. The effects of L-arginine and NG-monomethyl L-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation. Br J Pharmacol 98, 1080–1082. Klinge, E. & Sjöstrand, N.O. 1974. Contraction and relaxation of the retractor penis muscle and the penile artery of the bull. Acta Physiol Scand 93, Suppl. 420, 1–88. Klinge, E. & Sjöstrand, N.O. 1977. Comparative study of some isolated mammalian smooth muscle effectors of penile erection. Acta Physiol Scand 100, 354–367. Rees, D.D., Palmer, R.M.J., Hodson, H.F. & Moncada, S. 1989. A specific inhibitor of nitric oxide formation from l-arginine attenuates endo-thelium-dependent relaxation. Br J Pharmacol 96, 418–424. Saenz DE, Tejada I., Blanco, R., Goldstein, I., Azadzoi, K., De Las, Morenas A., Krane, R.J. & Cohen, R.A. 1988. Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue. Am J Physiol 254, H459–H467. Citing Literature Volume140, Issue2October 1990Pages 297-298 ReferencesRelatedInformation

The effect of adenosine analogues on guinea-pig endometrial secretion was studied in vitro at defined days of the estrous cycle. The adenosine analogues, 5'-N-ethylcarboxamideadenosine (NECA) and (N6-[(R)-1-methyl-2-phenylethyl]-adenosine (R-PIA), induced endometrial secretion at ovulation time (cycle days 16-1) and at implantation time (cycle days 6-7). The secretory response to NECA was antagonized by 8-p-sulfophenyltheophylline. Scopolamine had no effect on secretion induced by the adenosine analogues. Endometrial secretion induced by field stimulation was inhibited by NECA but not by R-PIA at ovulation time. At implantation time, both NECA and R-PIA reversed the response to field stimulation to values below the basal resting level. The latter effect was antagonized by phentolamine. These findings suggest that adenosine analogues can induce guinea-pig endometrial secretion by action at stimulatory adenosine receptors, and concomitantly inhibit secretomotor neurotransmission.

The effects of acupuncture on survival of ischaemic musculocutaneous flaps were investigated in the rat. A dorsal cranially based standard flap (2×7 cm) was elevated and sutured back in position. The percentage survival of the flaps was estimated after 6 days. Manual acupuncture, electro‐acupuncture but not superficial acupuncture significantly increased the survival of the flaps compared to untreated controls. The highest flap survival (92%) was obtained with repeated post‐operative high‐intensity electroacupuncture. It is concluded that acupuncture treatment markedly increases experimental flap survival and may be of clinical importance for treatment of local ischaemia.

The effect on blood flow of electro-acupuncture (EA) injection of substance P (SP) and calcitonin generelated 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 (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.

The effect of blood flow on transcutaneous electrical nerve stimulation (TENS) and injection of calcitonin gene-related peptide (CGRP) was studied in a musculocutaneous flap of the rat, using laser Doppler flowmetry. The circulatory border was estimated before and after treatment. It was shown that repeated treatments with TENS gradually increased the blood flow, moving the circulatory border distally more than 100% after three treatments. Injection of NaCl into the dorsal central vein of the flap resulted in no increase in blood flow, whereas CGRP 10(-10) M increased the blood flow, so that the circulatory border moved distally 70% and 60%, respectively.

The effect of transcutaneous electrical nerve stimulation (TENS) on the survival of a dorsal musculocutaneous flap was studied in the rat. Postoperative TENS treatment significantly increased the flap survival area in groups of rats receiving different modes of TENS. The flap survival area was up to 95% in the TENS-treated groups compared with 33-45% in the control groups. Repeated (3 days) high intensity (20 mA), high-frequency (80 Hz) TENS applied segmentally at the base of the flap was shown to be the most effective treatment in increasing the flap survival. Preoperative TENS did not increase flap survival area compared with untreated controls. It is concluded that postoperative TENS treatment markedly increases the experimental flap survival area and may be of clinical value for treatment of local ischaemia.

In the present investigation we have examined the possibility that endogenous purines may act as neuromodulatory agents in the human fallopian tube, using the selective adenosine receptor antagonist 8-p-sulfophenyltheophylline (PSOT). PSOT applied to untreated preparations enhanced the contractile responses to transmural nerve stimulation in the human fallopian tube, both in the secretory and proliferative hormonal phases. Furthermore, PSOT enhanced nerve-induced [3H]noradrenaline release during both hormonal phases. This can be taken as indirect evidence that endogenous purines inhibited the adrenergic neuroeffector transmission under the experimental conditions. The inhibitory effect presumably was exerted at both pre- and postjunctional adenosine receptors.

The effects of adenosine and adenosine analogues on nerve-induced contractile responses and [3H]noradrenaline ([3H]NA) release, were studied in the isthmic part of human oviducts. Adenosine and L-N6-phenylisopropyladenosine (L-PIA) could enhance neurogenic contractile responses in preparations obtained mainly in the proliferative phase. At higher concentrations, adenosine derivatives inhibited contractile responses to nerve stimulation in both proliferative and secretory phase, with the potency order: 5′-N-ethylcarboxamideadenosine (NECA) ⩾ L-PIA ⪢ D-PIA. This indicated actions at both stimulatory A1- and inhibitory A2-receptors. Adenosine, L-PIA and NECA but not D-PIA inhibited [3H]NA release during nerve stimulation. The relative potency order for the prejunctional inhibition was compatible with an action at A1-receptors. Furthermore, adenosine was found to modulate nerve-induced contractions via postjunctional stimulatory A1- and inhibitory A2-like receptors. The postjunctional effects may be influenced by cyclic hormonal changes. The adenosine antagonist 8-p-sulfophenyltheophylline (PSøT) reversibly antagonized the stimulatory and inhibitory effects by adenosine and analogues.

Isolated strips from isthmic and ampullary muscle layers of the human fallopian tube were investigated with the sucrose-gap technique and in organ baths. Generally good correlation existed between electrical and mechanical activity, but dissociation was also noted. The isthmic external longitudinal layer (IEL) was characterized by slow waves of depolarization and broad 'spikes'. Tonic contraction followed depolarization, and phasic waves followed the spikes. In the other layers, regular spikes and phasic contractions dominated. Late in the menstrual cycle, more irregular patterns and slow waves, which could synchronize spike activity, were found. Automaticity tended to be highest in the late proliferative phase. Active response to stretch was best demonstrated in IEL. Excitatory alpha-adrenergic responses (hypopolarization, firing and contraction) to noradrenaline and nerve stimulation dominated in the IEL. In the other layers, beta-adrenergic inhibition prevailed. Non-adrenergic, non-cholinergic neurogenic inhibition was demonstrated. Decrease in spike frequency and hyperpolarization seemed to be as prominent as during beta-adrenergic inhibition. Muscarinic stimulation by acetylcholine was recorded as depolarization, spikes and contraction. However, a role for cholinergic nerves could not be defined. Thus, the human oviductal smooth muscle belongs to the single unit category; its activity can be modified during the menstrual cycle, by stretch and by excitatory and inhibitory nerves.

Effects of adenosine and adenosine analogues on spontaneous contractility of the human fallopian tube during different phases of the menstrual cycle were studied. In isthmic preparations, a stimulatory effect by L-N6-phenylisopropyladenosine (L-PIA), with preference for adenosine A1-receptors, was seen mainly during the proliferative phase. In ampullary preparations, stimulation by L-PIA was seen both in the secretory and proliferative phases. Adenosine and 2-chloroadenosine exerted similar stimulatory effects. 5'-N-ethylcarboxamide-adenosine (NECA), with selectivity for adenosine A2-receptors, or D-PIA never showed a stimulatory effect. At concentrations above those needed for stimulation, adenosine, 2-chloroadenosine and L-PIA inhibited spontaneous contractions, in common with NECA and D-PIA. Here, NECA was more potent than L-PIA. The D-PIA and L-PIA were equipotent. The inhibition was seen during the whole menstrual cycle. The competitive adenosine antagonist 8-p-sulphophenyltheophylline (PSøT) reversibly antagonized the stimulatory and inhibitory effects elicited by adenosine and the analogues. The PSøT alone could exert a stimulatory or an inhibitory action on spontaneous contractility. We suggest that adenosine can modulate contractile activity in the human fallopian tube via stimulatory A1-and inhibitory A2-receptors. These receptors are located on the smooth muscle cells, and might act via cAMP. The relative receptor dominance may be influenced by cyclic hormonal changes.

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 × 1010 to 107 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.