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Background: Microvascular submandibular gland transplantation (SMGT) for severe dry eye disease (DED) has rarely been reported in the literature. The aim of this study was to report a case series of SMGT with the special focus on monitoring and management of postoperative vascular compromise., Methods: Using a retrospective single-cohort study design, the investigators enrolled a sample of DED patients undergoing SMGT in a Chinese university hospital during 1999 and 2021. The main outcomes were baseline and surgical data, post-operative manifestations, and surgical results. Descriptive, uni- and bivariate statistics were computed with the significant P < 0.05., Results: During the study period, 220 DED patients (55.9% female) with a mean age of 32.66±14.47 years underwent SMGT. Vascular compromises occurred in 27 grafted glands (12.3%; 22 venous compromises and 5 arterial compromises) at a median of 27 h(range, 3.3 to 288 h) after surgery. Harden texture and swelling of the covering skin flap of the donor indicated venous compromises, while some specific sign was absent for arterial compromise. The accompanying vein of the facial artery (FAV) as a donor's vein was associated with less vascular compromise compared to the anterior facial vein (AFV). Timely reexploration was performed in 25 glands (92.6%), with a salvaged rate of 48%, and more venous compromises were salvaged compared to artery compromises (54.6% vs. 0%, P = 0.047). Temporary hypersecretion on postoperative 2-5 days was noticed in the grafted glands with no or salvaged vascular compromise (Schirmer's test, 35 mm/5 min and 37 mm/5 min, respectively, P = 0.749), while they were absent for the 15 surgically failed grands (Schirmer's test 0 mm/5 min, P<0.001)., Conclusions: Vascular compromise appears to be a common complication of SMGT. Postoperative hypersecretion of the grafted glands may indicate good circulation, and the use of FAV as the donor's vein could help to decrease the risk of vascular compromise., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

A male patient underwent microvascular transplantation of an autologous submandibular gland and its associated (Wharton's) duct for management of very severe right keratoconjunctivitis sicca due to Stevens-Johnson syndrome; due to hypersecretion, the gland was later removed in toto. Twenty-two years later, he presented with a nontender, sausage-like mass lying subcutaneously in the right temple. Intraoperatively a fluctuant tubular mass passing from the temporalis fossa to the superotemporal conjunctiva was identified and excised intact. Histology showed a slightly proteinaceous fluid within a duct lined with cuboidal epithelium, this being compatible with Wharton's duct. This case highlights that iatrogenic causes should be considered with any history of periocular injury or surgery., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Microvascular dysfunction plays a fundamental role in the pathogenesis of salivary gland disorders. Restoring and preserving microvascular integrity might therefore represent a promising strategy for the treatment of these pathologies. The mechanisms underlying microvascular dysfunction in salivary glands, however, are still obscure, partly due to the unavailability of adequate in vivo models. Here, we present a novel experimental approach that allows comprehensive in vivo analyses of the salivary gland microvasculature in mice. For this purpose, we employed different microscopy techniques including multi-photon in vivo microscopy to quantitatively analyze interactions of distinct immune cell subsets in the submandibular gland microvasculature required for their infiltration into the surrounding parenchyma and their effects on microvascular function. Confocal microscopy and multi-channel flow cytometry in tissue sections/homogenates complemented these real-time analyses by determining the molecular phenotype of the participating cells. To this end, we identified key adhesion and signaling molecules that regulate the subset- and tissue-specific trafficking of leukocytes into inflamed glands and control the associated microvascular leakage. Hence, we established an experimental approach that allows in vivo analyses of microvascular processes in healthy and diseased salivary glands. This enables us to delineate distinct pathogenetic factors as novel therapeutic targets in salivary gland diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Uhl, Braun, Dominik, Luft, Canis and Reichel.)

Knowledge of variant course and branching pattern of the facial artery gains importance in the surgeries of upper neck and face. The authors report a unilateral anomalous course and a redundant loop of right facial artery as seen in an adult male cadaver. The right facial artery had its origin from the external carotid artery. It pierced through the submandibular salivary gland and formed a redundant loop at the base of the mandible. Its further course and branching pattern was normal. This case could be important for radiologists, plastic surgeons and craniofacial surgeons.

Our previous studies indicated that YIGSR-A99 peptides chemically conjugated to fibrin hydrogel (FH) and applied to wounded submandibular gland (SMG) in vivo, formed new organized salivary tissue, whereas wounded SMG treated with FH alone or in the absence of a scaffold showed disorganized collagen formation and poor tissue healing. While these studies indicated that damaged SMG grow and differentiate when treated with FH containing L1 peptide, they were performed only in female mice. However, there is a well-established sexual dimorphism present in mouse SMG (e.g., males develop well-differentiated granular convoluted tubules, but these structures are poorly developed in females) and little is known about how these sex differences influence wound healing events. Therefore, the goal of this study was to conduct comparative analyses of regeneration patterns in male and female mice using L 1p -FH in a wounded SMG mouse model. Particularly, we focused on sex-dependent wound healing events such as macrophage polarization, vascularization, tissue organization, and collagen deposition, and how these events affect salivary gland functioning.

The natriuretic peptide (NP) system comprises of three ligands, the Atrial Natriuretic Peptide (ANP), Brain Natriuretic peptide (BNP) and C-type Natriuretic peptide (CNP), and three natriuretic peptide receptors, NPRA, NPRB and NPRC. Here we present a comprehensive study of the natriuretic peptide system in healthy murine and human submandibular salivary glands (SMGs). We show CNP is the dominant NP in mouse and human SMG and is expressed together with NP receptors in ducts, autonomic nerves and the microvasculature of the gland, suggesting CNP autocrine signalling may take place in some of these glandular structures. These data suggest the NP system may control salivary gland function during homeostasis through the regulation of electrolyte re-absorption, neural stimulation and/or blood vessel wall contraction/relaxation. We also show abnormal expression of NPRA in the stroma of a subset of human SMGs resected from patients diagnosed with oral squamous cell carcinoma (OSCC) of non-salivary gland origin. This finding warrants further research to investigate a possible correlation between early OSCC invasion and NPRA overexpression.

Electron microscopic investigations of the animals' submandibular gland, conducted in 6 weeks of the experiment, established that ultrastructural changes increase in glandular cells of terminal secretory units in comparison with early period of the experiment. Serocytes have osmiophilic, rather small or picnotic nuclei. Perinuclear spaces of karyolemma are uneven, external nuclear membrane forms local protrusions. Electron density of the karyoplasm is significant, appearing homogenous, nuclei are not observed. Evident submicroscopic changes in blood capillaries of the submandibular gland in experimental diabetes mellitus indicate the impairment of blood-tissue barrier and transcapillary exchange. Deep destructive modifications of all branches of microcirculatory blood flow of the submandibular gland are observed in 8-week course of experimental diabetes mellitus. As compared with the 6th week of investigation, a reliable slight dilation of organ artery diameter, dilation of the diameter of interlobular arterioles, dilation of the diameter of intralobular (precapillary) arteriole and dilation of the capillary diameter were observed. Dilation, as compared to 6th weeks of the experiment, of postcapillary venules was observed. Compared to the indices of the 6th weeks of the experiment, an index of trophic activity of the submandibular gland tissuereaches its maximum meaning and an index of packing density of the capillaries reaches its minimum meaning. Capillary network loses delicate, tortuous pattern and often breaks due to destruction of the capillary component. Arteriovenous anastomoses dilate and blood from the arterioles flows into the venous bed avoiding destructed capillaries. Venules are dilated; thin-walled, retained fragments of the capillaries are significantly dilated in some areas. Swelling of connective tissue stroma and significant swelling of the interstitium are observed. Walls of the capillaries and venules are deformed. The walls of the arterioles are thickened due to plasmorrhagia, sclerosis and hyalinosis.

Chronic sclerosing sialadenitis, also known as Küttner's tumour, is a chronic inflammatory condition affecting the salivary glands. We present the case of an arteriovenous vascular malformation (AVM) of the right submandibular gland mimicking a Küttner's tumour on ultrasound scan in a 63-year-old woman. Examination revealed a 2 cm firm, mobile, non-pulsatile, right-sided submandibular mass with no overlying skin changes but with mild tenderness to palpation. Histological appearances revealed an AVM associated with localised fatty metaplasia and glandular atrophy. Although rare, AVMs should be considered a differential diagnosis for a submandibular gland mass that gives unclear or unusual radiological appearances., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Keratoconjunctivitis sicca (KCS) is a relatively common disease that results in discomfort, tear film instability, visual impairment, and ocular surface damage. Artificial tear substitutes may be suitable for the treatment of mild KCS, but no effective treatment currently exists for severe KCS. Therefore, this study evaluated the effectiveness of autologous microvascular submandibular gland transplantation in the treatment of severe KCS., Patients and Methods: A total of 61 eyes (56 patients) with severe KCS were treated with autologous submandibular gland transplantation from June 2002 to June 2017. The cephalic vein or the great saphenous vein was applied to solve the problem of unmatched veins., Results: In 53 cases (53 of 56, 94.6%), 58 glands (58 of 61, 95.1%) were transplanted successfully. The mean Schirmer I test value improved from 0.78 ± 0.84 mm preoperatively to 18.83 ± 5.72 mm in the stable period after transplantation. Epiphora (14 of 58, 24.14%) was the most common complication of this procedure. Other postoperative complications included venous thrombosis (6 of 61, 9.84%), local infection (2 of 58, 3.45%), xerostomia (2 of 53, 3.77%), duct fistula (1 of 58, 1.72%), sialolithiasis (1 of 58, 1.72%), and ranula (1 of 58, 1.72%)., Conclusions: Autologous microvascular submandibular gland transplantation is a credible and effective solution for severe KCS., (Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Extremity lymphedema is a pathological condition resulting from absence of lymph nodes and disease of lymphatic vessels, often due to oncologic clearance of lymph nodes. In recent years, vascularized lymph node transfer has become a rapidly emerging method of lymphatic reconstruction shown to lead to lymphatic regeneration. In particular, lymphatic flaps based on the submental artery have shown good results with its favorable donor site and available nodes. The lymph nodes here are in close relation to the submandibular gland and require careful dissection around and through the gland for safe harvest. We studied this region of the neck and describe the blood supply to the lymph nodes, their variable positions in relation to the gland, and our technique of dissecting through the submandibular gland while keeping the lymph nodes' hilar blood supply intact., Methods: We dissected 2 cadaver heads (4 sides of the neck) to study the submandibular and submental lymph nodes, where to locate them in relation to the submandibular gland and how best to dissect through the submandibular gland for access while keeping the hilar supply intact. We applied this knowledge in 6 clinical cases and provide a brief description of our "through-the-gland" dissection technique., Results: The submandibular lymph nodes may lie (1) superficial and posterior to the gland, (2) between the superficial and deep parts of the submandibular gland, or (3) anteriorly and submental. They are classified as superficial, deep, and submental, respectively. The through-the-gland dissection technique gave the surgeon improved access and exposure to the lymph nodes. It also facilitated safer dissection because their hilar blood supply is well visualized., Conclusions: The through-the-gland technique of harvesting vascularized submandibular lymph node flaps is a safe technique that allows the surgeon to clearly identify and preserve blood supply of lymph nodes.

Background and Aim: It has been speculated that impaired salivary flow contributes to abnormal acid clearance in patients with erosive esophagitis (EE). For easy and objective assessment of salivary function, we developed a salivary gland blood flow measurement technique using continuous-wave Doppler sonography. In the present study, we evaluated the salivary secretory function in patients with EE and those with nonerosive reflux disease (NERD) using this method., Methods: Doppler waveform analysis was performed on the facial artery to assess blood inflow to the submandibular gland of 30 healthy subjects (HS). Blood flow was compared before and after secretory stimulation with 1 mL of lemon juice. Saliva was simultaneously collected and weighed before and after stimulation. Continuous-wave Doppler sonography was also performed in patients with EE and NERD. The size of the submandibular gland was compared in 26 patients with EE, 41 patients with NERD, and 86 HS., Results: The submandibular gland blood flow increased after stimulation in all HS. Both within-day and day-to-day reproducibility were good. There was a significant correlation between the percent increase in the maximum velocity and the percent increase in salivary secretion. Although the size of the submandibular gland was not significantly different among the three groups, the percent increase in the maximum velocity in patients with EE was significantly smaller than that in HS., Conclusions: We have established an easy method of assessing salivary function in daily practice. This study revealed that a decrease in salivary secretory function is involved in the pathology of EE., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

We examined blood flow in the submandibular gland (SMGBF) and sublingual gland (SLGBF) during electrical stimulation of the central cut end of the lingual nerve (LN) in the urethane-anesthetized rats using a laser speckle imaging flow meter. LN stimulation elicited intensity- and frequency-dependent SMGBF and SLGBF increases, and the magnitude of the SMGBF increase was higher than that of the SLGBF increase. The increase in both glands was significantly inhibited by intravenous administration of the autonomic cholinergic ganglion blocker hexamethonium. The antimuscarinic agent atropine markedly inhibited the SMGBF increase and partly inhibited the SLGBF increase. The atropine-resistant SLGBF increase was significantly inhibited by infusion of vasoactive intestinal peptide (VIP) receptor antagonist, although administration of VIP receptor antagonist alone had no effect. The recovery time to the basal blood flow level was shorter after LN stimulation than after administration of VIP. However, the recovery time after LN stimulation was significantly delayed by administration of atropine in a dose-dependent manner to the same level as after administration of VIP. Our results indicate that 1) LN stimulation elicits both a parasympathetic SMGBF increase mainly evoked by cholinergic fibers and a parasympathetic SLGBF increase evoked by cholinergic and noncholinergic fibers, and 2) VIP-ergic mechanisms are involved in the noncholinergic SLGBF increase and are activated when muscarinic mechanisms are deactivated., (Copyright © 2015 the American Physiological Society.)

Hemangiomas of the submandibular space are very rare. Only 11 cases have been reported in the English literature, all of which were cavernous hemangiomas. In this report, we describe the case of a venous hemangioma in a 70-year-old woman. Ultrasound examination revealed a lobulated, homogeneous, hypoechoic mass, and minimal flow was detected on power Doppler evaluation. The mass and the submandibular gland were surgically excised, and the endothelium was found to be positive for CD31 and D2-40 markers, consistent with venous hemangioma. To our knowledge, this is the first reported case of a venous hemangioma in the submandibular space., (© 2014 Wiley Periodicals, Inc.)

Objective: To evaluate changes in salivary gland echostructure and vascularization after rituximab treatment in patients with primary Sjögren's syndrome (SS)., Methods: Twenty-eight patients with primary SS included in the multicenter, randomized, double-blind, placebo-controlled Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS) trial underwent salivary gland ultrasonography before the first placebo or rituximab infusion and then 6 months later. Trial inclusion criteria were scores of ≥50 mm on at least 2 of 4 visual analog scales (VAS) evaluating dryness, pain, fatigue, and global disease; and recent-onset (<10 years) biologically active primary SS and/or systemic primary SS. Patients were randomly assigned (1:1) to rituximab (1 gm at weeks 0 and 2) or placebo. Ultrasonography of both parotid and submandibular glands was performed to assess echostructure (using a semiquantitative score of 0-4, with improvement defined as a ≥1-point decrease), size of each gland, and vascularization based on the resistive index of the transverse facial artery of the parotid gland before and after lemon juice stimulation., Results: Of the 28 patients, 5 (18%; 3 in the placebo group and 2 in the rituximab group) had clinically detectable bilateral parotid gland enlargement at baseline. Parotid parenchyma echostructure improved in 50% of the rituximab-treated patients versus 7% of the placebo-treated patients (P = 0.03). In the submandibular glands, echostructure also improved in a larger proportion of rituximab-treated patients, although the difference was not significant (36% versus 7% of placebo-treated patients; P = 0.16). Gland sizes and resistive index remained unchanged., Conclusion: Ultrasonography showed improved salivary gland echostructure in patients with primary SS receiving rituximab, with no changes in salivary gland size or vascularization, 6 months after the first infusion., (© 2015, American College of Rheumatology.)

Objectives/hypothesis: Salivary gland stones (sialoliths) are a common cause of salivary gland enlargement, but such stones are uncommon in children. Low-flow vascular malformations of the head and neck region may develop phleboliths. Phleboliths within a venous malformation may be mistaken for a salivary stone given the similar calcified nature and location. We present two children who were referred to us for evaluation of submandibular gland sialoliths but were found to have venous malformations containing phleboliths. Multiple calcifications, calcifications > 1 cm, within a soft tissue mass separate from the substance of the submandibular gland suggest a diagnosis, of phleboliths within a venous malformation as opposed to a sialolith., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

To investigate the effects of ischemia/reperfusion on rat submandibular glands without denervation and the possible protective effects of ischemia preconditioning on the glands that experienced ischemia/reperfusion, in-situ ischemia/reperfusion and ischemia preconditioning experimental models of submandibular glands of healthy male Wistar rats were conducted. For ischemia/reperfusion groups, the glands were subjected to 90 min of ischemia without denervation, followed by 1, 12, 24, or 72 h of reperfusion. Ischemia preconditioning was achieved by 3 min of ischemia following 3 min of reperfusion, performed three times before ischemia/reperfusion. Salivary secretion, histological changes, alterations of tight junctions, myeloperoxidase activity, cellular apoptosis, and reactive oxygen species levels were detected. In ischemia/reperfusion glands, rising acute-inflammation responses, reduced tight-junction width, and increased myeloperoxidase activity, reactive oxygen species levels, and apoptotic cell numbers were observed, along with secretory dysfunction, especially at 1 and 12 h post-reperfusion, which seemed to gradually return to normal by 72 h post-reperfusion. In contrast, ischemia preconditioning showed the potential to ameliorate the injury-stress responses caused by ischemia/reperfusion. Our study revealed that ischemia/reperfusion could cause a series of injury-stress responses and ultimately lead to hyposecretion, independently of the parasympathetic nerve supply, which might play an important role in the early-phase dysfunction of the transplanted glands. Ischemia preconditioning could protect the involved glands and improve ischemia/reperfusion-induced hyposecretion., (© 2014 Eur J Oral Sci.)

Background/aim: Atherosclerotic-occlusive changes could be observed in orofacial branches of the external carotid artery. Atherosclerosis-induced ischemia caused alteration in production and release of endothelial factors. The aim of this study was to investigate the influence of carotid artery occlusion (10, 30 and 60 min) on vascular effects of norepinephrine (NOR) and neuropeptide Y (NPY) in the isolated glandular branch of the rabbit facial artery, the main feeding artery for the submandibular gland., Method: Changes in isometric tension were recorded in organ bath studies with arterial rings, before and after carotid artery occlusion., Results: Concentration-dependent vasocontractile effect of NOR was significantly augmented after 30 and 60 min of carotid occlusion, but only in the rings with intact endothelium. Given alone, NPY showed no effect in isolated glandular branch of the rabbit facial artery, but enhanced NOR vasoconstriction in all the investigated rings. NOR vasocontractile effect enhancement in the presence of NPY was attenuated after 30 and 60 min of carotid occlusion. Also, enhancement of NOR vasoconstriction by NPY was significantly higher in endothelium-intact rings compared to endothelium-denuded rings obtained after 30 and 60 min of carotid occlusion., Conclusion: The present investigation provides results of increased vasocontractile effect of NOR and decreased enhancing effect of NPY on NOR vasoconstriction in the rabbit facial artery after carotid occlusion that is related to altered endothelium function.

Intensity-time gradients (ITGs) of contrast-enhanced ultrasound (CEUS) can be used for non-invasive monitoring of gland-preserving treatment effects in sialolithiasis-related chronic sialadenitis as well as for imaging vascularization in tumors. The aim of this clinical trial was to evaluate feasibility to distinguish different entities of submandibular gland disease including inflammatory alterations of the submandibular gland as well as benign and malignant tumors. In this prospective clinical study, ITGs in 30 patients with sialolithiasis-related chronic sialadenitis or an unilateral submandibular mass and 18 disease-free submandibular gland controls were quantitatively analyzed by CEUS using the contrast agent SonoVue. In addition, clinical complaints according to visual analog scales (VAS) were documented. VAS data documented significantly less complaints only in benign tumors compared with the other pathologies of the submandibular gland. In parallel, CEUS-derived ITGs revealed significantly reduced ITGs only in benign tumors (n = 5) compared to the controls (n = 18). Despite of comparably reduced wash-in velocities in malignant lesions (n = 3) statistical significance was not reached. Chronic sialadenitis (n = 18) and its sclerosing variant (Küttner tumor, n = 4) revealed comparable ITGs as controls. Tumors of the submandibular gland present with reduced functional microcirculatory networks comparing with healthy gland controls and chronically inflamed submandibular glands. Thus, dynamic CEUS-derived ITGs in combination with conventional clinical measures--for example VAS--appear as a safe and promising strategy for non-invasive diagnostic workup of submandibular lesions and warrant further validation in a larger set of patients.

Objective: To evaluate the feasibility of microvascular autologous transplantation of partial submandibular gland (SMG) to prevent or reduce epiphora in severe keratoconjunctivitis sicca (KCS)., Methods: A total of 39 patients with KCS, covering 42 eyes, were randomised to undergo transplantation of partial or total SMG from January 2006 to December 2009. Clinical data of survival rate of transplanted SMG, ophthalmologic features of best-corrected visual acuity, Schirmer test results, break-up time (BUT) of tear film, fluorescence staining, incidence of postoperative epiphora and frequency of subsequent surgery were compared between two groups., Results: Total SMG transplantation was performed in 22 eyes, and partial SMG transplantation was performed in the other 20 eyes. All transplanted SMGs survived. Microvascular crisis occurred in one case of partial SMG transplantation, but the gland survived after exploration to remove the venous thrombus. Obstruction of the ductal orifice in one case of partial SMG transplantation was resolved by reconstruction of the ductal orifice. Symptoms of dry eyes disappeared, and patients were able to discontinue use of artificial tears. Severe epiphora occurred in 6 eyes undergoing partial SMG transplantation and in 19 eyes undergoing total SMG transplantation (p<0.01). Surgical reduction was performed in 6 eyes undergoing partial SMG transplantation and 18 eyes undergoing total SMG transplantation (p<0.01)., Conclusions: Microvascular transplantation of partial SMG is feasible and effective for severe KCS and does not decrease the survival rate of transplanted SMG. For ample SMGs with normal function, transplantation of partial SMG alleviates the symptoms of dry eye and significantly reduces the incidence of severe postoperative epiphora.

It is known that aquaporin (AQP) 5 expression in the apical membrane of acinar cells in salivary glands is important for the secretion of saliva in rodents and humans. Although heat acclimation enhances saliva secretion in rodents, the molecular mechanism of how heat induces saliva secretion has not been determined. Here, we found that heat acclimation enhanced the expression of AQP5 and AQP1 in rat submandibular glands concomitant with the promotion of the HIF-1α pathway, leading to VEGF induction and CD31-positive angiogenesis. The apical membrane distribution of AQP5 in serous acinar cells enhanced after heat acclimation, while AQP1 expression was restricted to the endothelial cells in the submandibular glands. A network of AQPs may be involved in heat-acclimated regulation in saliva secretion. Because AQPs probably plays a crucial role in saliva secretion in humans, these findings may lead to a novel strategy for treating saliva hyposecretion.

Objective: Amisulpride is suggested for treatment of clozapine-induced sialorrhea. However, objective measurements of its effectiveness are lacking and, preclinically, amisulpride has no effect. We currently hypothesise that amisulpride acts by reducing the nervous- rather than the clozapine-driven salivary secretion., Material and Methods: Effects of intravenous amisulpride (as well as of clozapine and raclopride, a dopamine D2/D3 antagonist) were investigated in rats, including those subjected to chronic preganglionic parasympathetic denervation (submandibular glands) or combined postganglionic parasympathetic and sympathetic denervation (parotid glands). In duct-cannulated glands, secretion was evoked reflexly, at low and maximum flow rates, and by electrical stimulation of the parasympathetic and sympathetic innervations, and administration of autonomimetics (including substance P)., Results: Unlike clozapine, amisulpride had no effect on the reflexly evoked secretion at maximum rate. With respect to reflex secretion at low rate and to the secretion evoked by muscarinic, α-adrenergic, β-adrenergic and substance P receptors, amisulpride (in contrast to raclopride) dose dependently potentiated the responses. Amisulpride had no effect on gland blood flow., Conclusions: No support for any inhibitory influence of amisulpride was found. Conversely, amisulpride universally enhanced secretion, suggesting that amisulpride is a potential drug for dry-mouth treatment. The mechanism behind the potentiation is currently unknown., (© 2012 John Wiley & Sons A/S.)

Purpose: Autologous microvascular submandibular gland (SMG) transfer is an effective treatment for severe keratoconjunctivitis sicca (KCS). However, epiphora (excessive tear secretion) may occur after the successful transfer of whole submandibular gland because tear secretion level is closely related to the size of the transferred gland. The aim of this study was to investigate the microanatomy of SMG to explore the possibility of partial SMG transfer to prevent postoperative epiphora., Materials and Methods: Sixty intact and histologically normal human SMGs from patients with benign tumor of the mandible who underwent vascularized mandibular reconstruction and removal of the SMG for anastomosis of the blood vessels were included in the study. SMGs were perfused with methacrylate to form resin casts of blood vessels and ducts. The length and diameter of the blood vessels and ducts in the casts were measured using a sliding caliper. The numbers of lobules, distribution of arteries, veins, and ducts, as well as the relationship among them, were analyzed., Results: The resin cast of the gland showed a treelike structure, with the vessels gradually dividing into multiple branches. The arteries, veins, and ducts run in parallel and were roughly divided into 3 levels: from the stem extending into the main branches (level I), into the narrower secondary branches (level II), and then the secondary branches subsequently divided into terminal branches (level III). The structures of the blood vessels and ducts were similar at each level in the lobules. In the vein casts, communicating vessels were found between the anterior facial vein and the concomitant vein of the facial artery., Conclusion: The characteristic treelike structure of the SMG vascular and ductal system may provide useful information for partial gland transfers., (Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Blood collection in mice can be a challenge, in particular for samples used for coagulation analysis as initiation of coagulation during the procedures can influence the results. Blood collection from the retrobulbar venous plexus is commonly used but the method remains controversial. Several alternatives exist but not all are applicable to mice with a compromised coagulation system because of subsequently excessive bleeding. We therefore wanted to explore whether blood collection by puncture of the submandibular vein could replace blood collected from the retrobulbar venous plexus during pharmacokinetic and pharmacodynamic studies in mice lacking coagulation factor VIII (FVIII). The plasma concentrations of recombinant activated factor VII were independent of the blood collection method in a pharmacokinetic study. The same applied to the thromboelastographic profile of mice with normal coagulation in a pharmacodynamic study. However, excessive haemorrhages were observed in all FVIII knockout mice after a single puncture of the submandibular vein and 60% of the mice were euthanized 2-4 h after the blood collection. In contrast, no or only slight haemorrhage was observed in animals subjected to blood collection from the retrobulbar venous plexus. No signs of distress determined by blood glucose level or clinical abnormalities of the eye were observed after puncture of the retrobulbar venous plexus. In conclusion, blood collected by puncture of the submandibular vein and retrobulbar venous plexus has a quality which allows it to be used in coagulation assays. However, because of excessive bleedings, puncture of the submandibular vein is not recommended in mice lacking FVIII.

Objectives: Submandibular vasodilatory responses are impaired in male streptozotocin-diabetic rats. However, the effects of diabetes on submandibular vascular reactivity in female rats have not been examined. The purpose of this study was to determine whether there are gender differences in the effects of diabetes on parasympathetic vasodilatation in the rat submandibular gland., Methods: Diabetes was induced using streptozotocin, and vascular responses (calculated as the % increase in submandibular vascular conductance) to parasympathetic stimulation (1-10 Hz) were measured using laser-Doppler flowmetry. To estimate the relative contributions of nitric oxide (NO), prostacyclin (PGI2) and endothelium-derived hyperpolarizing factor (EDHF), vascular conductance was measured before and after inhibition of cyclooxygenase (COX) and NO synthase (NOS)., Results: Frequency-dependent increases in blood flow were observed in both male and female rats, but the contribution of EDHF was greater in females than in males. Further, PGI2 appeared to play a role only in males. Vasodilatory responses were diminished in all diabetic animals, and when compared with their respective controls the degree of impairment was similar in males and females. However, in diabetic males inhibition of COX and NOS had little or no effect, whereas inhibition of NO, but not COX, resulted in a further significant decrease in vascular responses in diabetic females., Conclusions: Parasympathetic vasodilatation in the rat submandibular gland is diminished equally in diabetic males and females. However, in males diabetes predominantly impairs PGI2- and NO-dependent vasodilatation, whereas in females the contribution of EDHF-mediated pathways are affected and NO-dependent vasodilatation is preferentially maintained., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Hyposecretion occurs in most patients early after submandibular gland autotransplantation for severe keratoconjunctivitis sicca. Endogenous transient receptor potential vanilloid subtype 1 (TRPV1) has been recently demonstrated in rabbit submandibular glands, and activation of TRPV1 by capsaicin increases secretion in isolated glands, but the TRPV1-mediated secretory mechanism remains to be elucidated. The purpose of this study was to verify whether activation of TRPV1 by capsaicin could improve the secretion of transplanted gland and its underlying mechanism. The salivary flow of the transplanted glands was significantly decreased, and the mRNA and protein levels of TRPV1 and aquaporin 5 (AQP5) were downregulated in the transplanted glands. Topical capsaicin cream increased secretion and upregulated levels of TRPV1 and AQP5 in transplanted glands. Moreover, in cultured submandibular gland cells, capsaicin increased the mRNA expression of AQP5 and led to redistribution of AQP5 from the cytoplasm to the plasma membrane via TRPV1 activation. Capsaicin enhanced the phosphorylation of extracellular signal-regulated kinase (ERK). Preincubation of cells with PD98059, an inhibitor of ERK kinase, suppressed the capsaicin-induced mRNA expression of AQP5. In summary, the capsaicin-induced secretory mechanism involved activation of TRPV1 and upregulation of AQP5 in an ERK-dependent manner and promoted the redistribution of AQP5 in submandibular gland cells. Activation of TRPV1 may provide a new therapeutic strategy to improve submandibular gland hypofunction.

Objectives: The influence of carotid artery occlusion (10, 30 and 60 min) on regulatory mechanisms implicated in the vasorelaxant responses of isolated glandular branch of rabbit facial artery to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) was examined., Design: In organ bath studies with arterial rings precontracted with phenylephrine (1 microM), before and after carotid artery occlusion, changes in isometric tension were recorded., Results: Endothelium-dependent vasorelaxation by ACh and endothelium-independent vasorelaxation by VIP were significantly reduced, started from 30 and 10 min of carotid occlusion, respectively. Inhibitory effect of indomethacin on ACh vasorelaxation was enhanced whilst effect of N(G)-nitro-L-arginine reduced, started from 30 min of carotid occlusion. Sodium nitroprusside-induced vasorelaxation was not changed after carotid occlusion. Inhibition of VIP vasorelaxation by L-N(omega)-nitroarginine-2,4-L-diaminobutyric-amide, was reduced, started from 30 min of carotid occlusion. Forskolin enhanced VIP-induced vasorelaxation in control rings but this effect was reduced started from 30 min of occlusion. In the presence of VIP, vasorelaxant effect of ACh was increased; the increase was reduced, started from 10 min of carotid occlusion., Conclusions: The present investigation provides evidence for the decreased responsiveness to both, ACh-endothelium-dependent and VIP-endothelium-independent vasorelaxation in rabbit facial artery after carotid occlusion. In addition, the data suggest that ischaemia alters contribution of endothelial nitric oxide (eNO) and prostaglandin to ACh, and vascular smooth muscle's cAMP and neuronal NO to VIP vasorelaxant effects., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Collection of blood from the submandibular vein allows simple and rapid processing of many animals without anesthesia and facilitates rapid recovery with no signs of pain and discomfort in the mice. Here we compared the submandibular vein and retroorbital plexus blood collection methods, to determine the potential effect of the sampling technique on several clinical biochemistry parameters in C57BL/6J mice. We found statistically significant differences for 8 of the 9 biochemical parameters studied between the 2 blood sampling techniques. Compared with samples collected from the retroorbital plexus, blood obtained from the submandibular vein had higher levels of AST, ALT, protein, albumin, triglycerides, total cholesterol, and creatinine. Glucose values of retroorbital blood were higher than those from the submandibular vein. Urea levels were similar for both sampling techniques. Our results demonstrate that the technique used to obtain blood samples affects parameters commonly used to assess animal health. We recommend caution when comparing results of biochemical analysis of blood obtained from the submandibular vein in mice with reference values obtained by other blood sampling techniques.

Objective: To summarize the complications' prevention and nursing experience for patients after autologous transplantation of the microvascular submandibular gland for severe keratoconjunctivis sicca., Methods: Retrospective analysis of 141 patients(151 sides) after autologous microvascular submandibular gland transfer operation was undertaken to record the timing and incidence of major complications and to summarize the nursing experience., Results: The main complications after the transplantation were: vascular crisis, catheter obstruction, salivary fistula and temporary paralysis of hypoglossal nerve. Related nursing measures in response to these complications were discussed., Conclusion: Targeted nursing interventions for patients with autologous transplantation the submandibular gland have a positive effect on the prevention of the surgical complications.

Previous studies suggest that NO- and PGI(2)-independent pathways play a greater role in parasympathetic vasodilatation in the submandibular glands (SMG) of female than of male rats. Thus, the purpose of this study was to determine whether estrogen and progesterone influence the relative contributions of NO and PGI(2) to parasympathetic vasodilatation in the SMG. Vascular responses to chorda-lingual nerve stimulation were examined in sham-operated (SHAM) and ovariectomized (OVX) female rats and in OVX rats treated with either 17beta-estradiol alone or a combination of 17beta-estradiol and progesterone. Compared with SHAM animals, increases in vascular conductance in OVX rats were reduced at 1, 2 and 5 Hz (p<0.05). Blood flow responses in OVX+17beta-estradiol and OVX+17beta-estradiol+progesterone rats were indistinguishable from those observed in SHAM animals. Indomethacin had no effect on vasodilatation in SHAM and OVX+17beta-estradiol rats, but increased vascular responses in OVX animals (p<0.02). The addition of L-NAME resulted in a significant reduction in vasodilatation at all frequencies. In OVX rats treated with both estrogen and progesterone, indomethacin caused a reduction in vasodilatation and L-NAME further diminished the remaining responses. Under all conditions, vasodilatation was due largely, if not exclusively, to direct parasympathetic rather than antidromic sensory nerve activation. Finally, both neuronally-derived and endothelium-derived NO appeared to be responsible for the NO-dependent vasodilatation, but endothelium-derived NO became increasingly important as the frequency of stimulation increased. We conclude that estrogen and progesterone influence parasympathetic vasodilatation through combined effects on NO-, PGI(2)- and non-NO/PGI(2)-mediated pathways.

Objective: To analyse the reliability of concomitant venae of facial artery as the donor vein in microvascular autologous submandibular gland transfer., Methods: One hundred and seventeen cases with severe keratoconjunctivitis sicca treated by microvascular transfer of autogenous submandibular gland transfer from August of 1999 to November of 2007 were reviewed. The cases were divided into three groups according to their different donor veins, with group A using facial veins, group B using concomitant venae of facial artery, and group C using a vein near the duct. Group A and B were compared in terms of venous thrombosis rate and failure rate related to venous thrombosis., Results: Among 117 cases, there were 122 sides of submandibular gland transfers, with 93 in group A, 27 in group B, and 2 in group C. Postoperative venous thromboses rate was 15% in group A and 7% in group B, with significant difference (P < 0.01). The failure rate of transferred gland related to venous thrombosis was 8% in group A, and 7% in group B, with no significant difference (P > 0.05)., Conclusions: Concomitant venae of facial artery can be used as reliable donor vein in microvascular autologous submandibular gland transfer.

Introduction: Decreased vascular responses to salivary gland stimulation are observed in Sjögren's syndrome patients. We investigate whether impaired vascular responses to parasympathetic stimulation and muscarinic receptor activation in salivary glands parallels hyposalivation in an experimental model for Sjögren's syndrome., Methods: Blood flow responses in the salivary glands were measured by laser Doppler flowmeter. Muscarinic receptor activation was followed by saliva secretion measurements. Nitric oxide synthesis-mediated blood flow responses were studied after administration of a nitric oxide synthase inhibitor. Glandular autonomic nerves and muscarinic 3 receptor distributions were also investigated., Results: Maximal blood flow responses to parasympathetic stimulation and muscarinic receptor activation were significantly lower in nonobese diabetic (NOD) mice compared with BALB/c mice, coinciding with impaired saliva secretion in nonobese diabetic mice (P < 0.005). Nitric oxide synthase inhibitor had less effect on blood flow responses after parasympathetic nerve stimulation in nonobese diabetic mice compared with BALB/c mice (P < 0.02). In nonobese diabetic mice, salivary gland parasympathetic nerve fibres were absent in areas of focal infiltrates. Muscarinic 3 receptor might be localized in the blood vessel walls of salivary glands., Conclusions: Impaired vasodilatation in response to parasympathetic nerve stimulation and muscarinic receptor activation may contribute to hyposalivation observed in nonobese diabetic mice. Reduced nitric oxide signalling after parasympathetic nerve stimulation may contribute in part to the impaired blood flow responses. The possibility of muscarinic 3 receptor in the vasculature supports the notion that muscarinic 3 receptor autoantibodies present in nonobese diabetic mice might impair the fluid transport required for salivation. Parasympathetic nerves were absent in areas of focal infiltrates, whereas a normal distribution was found within glandular epithelium., Trial Registration: The trial registration number for the present study is 79-04/BBB, given by the Norwegian State Commission for Laboratory Animals.

This study was performed to evaluate the possibility of using reverse facial artery pedicled submandibular gland transfer for treating keratoconjunctivitis sicca. A reverse facial artery pedicled submandibular gland, including the duct, from a beagle dog was transplanted into the temporal region in the same animal. 99mTc pertechnetate scintigraphy was used to monitor graft viability, and the grafted glands were examined histologically 12 weeks after transplantation. Postoperative 99mTc pertechnetate scintigraphy demonstrated viable salivary gland tissue in the transplanted region. Histologically, some of the acinar cells in the graft had atrophied. The transplantation of a reverse facial artery pedicled submandibular gland was successful and may be a simple, reliable treatment for patients with keratoconjunctivitis sicca.

In order to functionally characterise the muscarinic vasodilator responses, effects of cholinergic agonists were studied on isolated preparations of the rat submandibular artery and vein and carotid and jugular vessels. Tentatively, a cholinergic regulatory mechanism having different effects on the arterial and venous vessels would enhance vascular fluid recruitment for the secretory response. In vitro functional findings were correlated to the expression and cellular location of the different receptors that were assessed by immunohistochemistry. In order to find in vivo correlates to the in vitro findings, the influence of muscarinic receptors on permeability was studied on the vasculature of the submandibular gland in anaesthetised rats. Staining for muscarinic M1 receptors occurred in the endothelium, and muscarinic M5 receptors, and possibly M3 also, were detected in the arterial smooth muscle. In venous endothelium, muscarinic M1 and M4 receptors occurred. In the jugular smooth muscle layer, staining for M1, and possibly also for M3, appeared. Muscarinic agonists caused arteries to relax and veins to contract. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine (L-NNA; 10(-4)M) markedly reduced the cholinergic-evoked relaxation of pre-contracted carotid arterial preparations. In the presence of 4-DAMP (10(-7)M), the relaxation to cholinergic agonists was inhibited. Pirenzepine (10(-5)M) did not only inhibit the relaxatory effects, but even reversed the effects, while it in the jugular vein abolished the cholinergic effects. The arterial nitric oxide-dependent response to muscarinic receptor stimulation consisted of two parts -- one sensitive to pirenzepine and 4-DAMP and the other to 4-DAMP only. Inhibition of the former part only, resulted in cholinergic arterial contraction. Also, the submandibular artery and vein responses to muscarinic receptor stimulation show a resemblance with those of the carotid and jugular vessels, i.e. a pronounced arterial relaxation and a contractile component in the venous response. In vivo examination of submandibular glandular vasculature by studying glandular permeability to Evans blue, confirmed the in vitro observations indicating muscarinic M1 receptors preserving perfusion pressure during the secretory process.

Unlabelled: Our objective was to evaluate the role of (99m)Tc-pertechnetate scintigraphy on microvascular autologous transplantation of the submandibular gland in patients with severe keratoconjunctivitis sicca (KCS)., Methods: (99m)Tc-Pertechnetate scintigraphy was performed on 106 patients with severe KCS. The patients were examined before surgery and at 1 wk and 3 mo afterward using a standardized protocol that included static scintigrams, time-activity curves, and delayed scintigrams to check the function and secretion of the major salivary glands. The scintigraphic findings were assessed visually. When possible, the scintigraphic findings were compared with the clinical appearance of the transplanted gland., Results: The function of all 4 major salivary glands was almost completely lost in 10 patients, indicating that these patients were not suitable for transplantation. The other 96 patients were treated by autologous transplantation of the submandibular gland. In 14 patients, the function of the major salivary glands was below normal. One patient's scintigram, obtained on the second day after surgery, showed no uptake of (99m)Tc-pertechnetate in the transplanted gland. Surgical exploration showed embolism of the artery of the transplanted gland. Scintigraphy was performed 1 wk after surgery in 90 patients. There was no uptake of (99m)Tc-pertechnetate in the temporal region in 8 patients, indicating that the glands were not revascularized. Scintigraphy showed obvious uptake of (99m)Tc-pertechnetate in the temporal region of the other 82 patients, indicating that the transplanted glands were viable. At more than 3 mo after surgery, scintigraphy was again performed on 30 patients. Scintigraphy after a 120-min delay showed that (99m)Tc-pertechnetate drained into the orbit through the duct of the transplanted gland in 26 patients. However, no secretion into the orbit was found in 4 patients, indicating obstruction of the duct., Conclusion: Scintigraphy plays an important role in microvascular autologous transplantation of the submandibular gland in patients with severe KCS. Scintigraphy can be used to select patients and donor glands, to evaluate the viability of the graft, and to check the patency of Wharton's duct of the transplanted gland.

Background: Transplanting a vascularized autologous submandibular gland (SMG) is considered an effective method to treat severe keratoconjunctivitis sicca. But the operation may fail due to the anatomic variances in the blood vessels of SMG. The present study aimed to investigate the submandibular glands at the microanatomy level., Methods: The microanatomy of blood vessels including arteries and veins of submandibular gland was investigated using 30 adult corpses and 60 submandibular glands were anatomized under a surgical microscope. The lengths and diameters of the arterial and venous glandular branches were measured using sliding caliper., Results: The submandibular gland was mainly supplied by the facial artery and submental artery, partly by the lingual artery and external jugular artery. The venous drainage of the submandibualr gland occurred through the anterior facial vein, the venae comitantes of facial artery, the vein close to the Whaston's duct (the hilum vein), and seldom drained to external jugular vein and other veins., Conclusions: The anatomy of SMG is a complicated structure. Determining the main blood vessels of the submandibular gland is very important to achieve a successful vascularized autologous SMG transplant.

Endothelial vasodilatory substances may play a central role in the local regulation of vascular tone. We hypothesized that these substances can mediate endothelium-dependent vasodilatory responses to acetylcholine (ACh) and vasoactive intestinal peptide (VIP) in the human submandibular artery. We evaluated the contributions of endothelial vasodilatory substances to vessel relaxation in response to ACh and VIP, using different inhibitors of endothelial vasodilation, the nitric oxide synthase inhibitor, the cyclo-oxygenase inhibitor, indomethacin, the potassium channel blocker, and 4-aminopyridine. ACh and VIP caused an endothelium- and concentration-dependent relaxation in this artery. ACh relaxation was completely blocked after the concomitant addition of N(G)-nitro-L-arginine and indomethacin. The vasorelaxant effect of ACh was not influenced by 4-aminopyridine. VIP relaxation was almost completely abolished by 4-aminopyridine, and was partly inhibited by N(G)-nitro-L-arginine, but was not affected by indomethacin. Thus, in the human submandibular artery, ACh and VIP produced endothelium-dependent vasodilation with different underlying mechanisms: release of nitric oxide (NO) and cyclo-oxygenase products for ACh, and release of NO and endothelium-derived hyperpolarizing factor for VIP.

The submandibular glands are subject to several pathologies that require excision. The most common problem that affects these salivary glands is sialadenitis combined with sialolithiasis. This problem occurs in the submandibular gland 10 times more frequently than it does in the parotid gland. Other illnesses frequently involving the submandibular glands are represented by sialadenosis and benign, malign, and intermediate neoplasms. Diagnosis of any disturbance in the submandibular gland involves both a clinical and instrumental (echography, traditional radiography [ortopantomography] and eventually computed tomography (CT) or magnetic resonance imaging) assessment. Surgery is the usual method of treatment of both chronic sialadenitis and neoplasms in the submandibular gland. A submandibular gland surgical approach can be cervical, intraoral, or endoscopic. The authors present their clinical experience with a total of 40 patients with illnesses involving the submandibular gland treated with submandibular gland excision by a transcervical approach. Their experience suggests that this approach entails a relatively simple procedure, involves low risks for the nerve structure around the gland, permits wide resection margins for neoplasms, and incurs little aesthetic damage.

Anterior surgery to the upper cervical spine, although rare, several successful approaches were described in the literature. To avoid the risks and limitations of transoral approach, the anterior retropharyngeal approach was developed. In this study, we describe our experience with anterior retropharyngeal approach to the upper cervical spine and discuss the significance of resecting the submandibular gland. From July 2001 to July 2004, we performed six anterior prevascular retropharyngeal approaches to the upper cervical spine. The series included five males and one female, ranging in age from 26 to 60 years (mean = 46). All six patients were intubated with nasotracheal cannula. The submandibular gland was mobilized and removed in all patients allowing adequate exposure of the arch of C1, C2, and C3 vertebral bodies. The anterior retropharyngeal approach permitted an adequate access to anteriorly situated lesions from C1 to C3 in all six patients, without the risks and limitations of transmucosal surgery. This approach allowed us to perform decompression of the spinal cord and reconstruction of the anterior column of the spine with bone graft and internal fixation. Careful removal of the submandibular gland provided better visualization of the arch of C1 and C2. No facial nerve palsy was seen in any of the six patients. Anterior retropharyngeal approach to the upper cervical spine combined with removal of the submandibular gland permits exposure of the anterior spine similar to that obtained by the transmucosal route, and provides a safe simultaneous arthrodesis and instrumentation during the primary surgical procedure without the potential contamination of the oropharyngeal cavity. Removal of the submandibular gland allows better exposure with less retraction and thus avoids severe injury to the mandibular branch of the facial nerve.

Purpose: Presently, treatments for xerostomia only target symptoms, as an active therapy method has not been established. Herein, we discuss the possibility of using a submandibular gland allograft technique for the disease., Materials and Methods: Using a vascularized submandibular gland transplantation method, we extracted portions of the submandibular gland, including the duct and chorda tympani branches, from beagle dogs and placed them into the submental region of age- and weight-matched dogs. We then measured the amount of saliva secretion and examined the grafted glands histologically., Results: Sufficient quantities of saliva were secreted from the grafted glands with pilocarpine treatment. Histologic findings showed that the acinar cells in the grafted and untreated contralateral glands had some atrophy, as compared with the normal glands; however, periodic acid Schiff staining showed that they produced saliva., Conclusions: Transplantation of vascularized submandibular glands into dogs was successful and may become a novel treatment strategy for patients with xerostomia.

Purpose: To describe an endoscopic technique for submandibular sialoadenectomy in humans, as well as the equipment, instrumentation, and pertinent anatomy., Materials and Methods: Six submandibular sialoadenectomies were carried out in 5 patients (3 women, 2 men; mean age, 26.6 years; range, 16 to 42 years) via a 15 to 20 mm neck incision for insertion of the endoscopic camera and surgical instruments., Results: All operations were successful without conversion to an open surgery. Operative time was 20 to 120 minutes (mean, 65 minutes). All patients were discharged the day after surgery. There were no postoperative complications (hematoma, nerve injury, infection). All patients experienced a mild degree of edema, which had resolved totally at the 6-month follow-up visit. All patients were satisfied with the outcome and especially the cosmetic result., Conclusions: Absence of extensive scars, nontraumatic dissection, and magnification of anatomic structures are the most obvious advantages of this innovative technique.

Transplantation and replantation of the submandibular gland with microvascular techniques were demonstrated in a previous study, with good gland survival. The application of radiation on the neck bed was attempted to address an actual clinical scenario in this study. Five canine submandibular glands were transplanted using microvascular techniques to the ipsilateral femoral system. Radiotherapy at a dosage level of 3,600 cGy using 600 cGy q.d was delivered to the nasopharyngeal and neck regions 2 weeks after transplantation. The transferred glands were then reintroduced into the original but radiated neck bed. The glands were harvested for histological examination 8 weeks later. Four of five canine submandibular glands can withstand microvascular transplantation and then replantation into a radiated neck bed for at least 8 weeks. However, the salivary function was depleted. The canine submandibular gland can survive the transplantation and replantation for at least 8 weeks in spite of precipitating radiation insult on the neck bed for 3 weeks. Neurorraphy is, however, essential to maintaining the glandular function.

The effects of muscarinic receptor antagonists on responses to electrical stimulation of the chorda-lingual nerve were determined in pentobarbitone-anesthetized sheep and correlated to the morphology of tissue specimens. Stimulation at 2 Hz continuously, or in bursts of 1 s at 20 Hz every 10 s, for 10 min induced similar submandibular fluid responses (19 +/- 3 vs. 21 +/- 3 microl x min(-1) x g gland(-1)), whereas vasodilatation was greater during stimulation in bursts (-52 +/- 4 vs. -43 +/- 5%; P < 0.01). Continuous stimulation at 8 Hz induced substantially greater responses (66 +/- 9 microl x min(-1) x g gland(-1) and -77 +/- 3%). While atropine (0.5 mg/kg iv) abolished the secretory response at 2 and 20 Hz (1:10 s), a small response persisted at 8 Hz (<5%). The "M1-selective" antagonist pirenzepine (40 microg/kg iv) reduced the fluid response at all frequencies tested (P < 0.05-0.01), most conspicuously at 2 Hz (reduced by 69%). Methoctramine ("M2/M4-selective"; 100 microg/kg iv; n = 5) had no effect on fluid or the vascular responses but increased the protein output at 2 (+90%, P < 0.05) and 8 Hz (+45%, P < 0.05). The immunoblotting showed distinct bands for muscarinic M1, M3, M4, and M5 receptors, and immunohistochemistry showed muscarinic M1 and M3 receptors to occur in the parenchyma. Thus muscarinic M1 receptors contribute to the secretory response to parasympathetic stimulation but have little effect on the vasodilatation in the ovine submandibular gland. Increased transmitter release caused by blockade of neuronal inhibitory receptors of the M4 subtype would explain the increase in protein output.

Ultrasound is expected to make a considerable contribution to drug delivery systems (DDSs). We tested the hypothesis that low-intensity focused ultrasound (LIFU) increases vessel permeability in the mouse submandibular gland without causing parenchymal damage. In a preliminary study, LIFU at 3 W/cm2 with a 50% duty cycle for 2 minutes did not cause histologic damage. We therefore applied LIFU to mouse submandibular gland at these conditions before and after injecting horseradish peroxidase. Single labeling laser scanning confocal microscopy revealed positive horseradish peroxidase staining around the excretory ducts in the mucous-producing part of the gland, but absence of staining in control glands. Immunostaining for fibrinogen was positive in the same region. Fibrinogen is an intravascular protein that does not pass through intact vessels. These findings suggest that LIFU increases vessel permeability and disruption without destruction. It is anticipated that this process will be useful in establishing a DDS that uses LIFU.

Volatile anesthetics have been known to suppress parasympathetic reflex vasodilatation in the lower lip and palate. However, in the submandibular gland, little is known about the effects of these anesthetics on the parasympathetic vasodilatation elicited by reflex and direct (i.e., non-reflex) activation of the parasympathetic vasodilator mechanisms. Although both parasympathetic vasodilatations were inhibited by isoflurane in a concentration- and time-dependent manner, the effects of continuous administration of the alpha(1)-adrenoceptor agonist methoxamine were markedly different: The reflex vasodilatation was not affected by methoxamine, while the direct vasodilatation was significantly reduced. Picrotoxin (GABA(A) receptor antagonist) attenuated the inhibitory effect of isoflurane on direct vasodilatation and the systemic arterial blood pressure. These findings suggest that the isoflurane-induced inhibitory effects on direct vasodilatation are produced by a decrease of peripheral vascular tone by GABAergic mechanisms, whereas those on the reflex vasodilatation are produced exclusively by the inhibition of the reflex center.

Parasympathetic vasodilatation in the rat submandibular gland is mediated by nitric oxide-dependent and -independent mechanisms (prostacyclin and endothelium-derived hyperpolarizing factor (EDHF)). The purpose of this study was to determine the influence of gender on the relative contributions of each pathway to nerve-stimulated vasodilatation. Absolute increases in perfusion (laser Doppler flowmetry) were similar in male and female rats (in arbitrary perfusion units: 6159+/-4530 and 5601+/-3877 at 2 Hz; 15645+/-6830 and 14848+/-6118 at 5 Hz; and 22418+/-7660 and 18878+/-5864 at 10 Hz). However, expressed as a percentage increase above resting values, stimulated perfusion was higher in males than in females (P<0.05). In males both Nomega-nitro-L-arginine methyl ester (L-NAME) and indomethacin partly blocked parasympathetic vasodilatation at all frequencies tested (P<0.05). In female rats significant reductions in nerve-stimulated perfusion were observed only at 2 and 5 Hz, but the effects of L-NAME were greater than in males (-64 compared with -45% at 2 Hz and -45 compared with -33% at 5 Hz, P<0.05). Indomethacin by itself had no apparent effect in females. The combined effects of L-NAME and indomethacin were dependent on the order of administration and on gender. Following L-NAME, indomethacin had no further effect in males or females. L-NAME reduced indomethacin-resistant vasodilatation in males and females, but the added effect of indomethacin was more pronounced in males. Finally, atropine-resistant vasodilatation was partly blocked by L-NAME, and the remaining vasodilatation was abolished by spantide I (substance P receptor antagonist). We conclude that NO, products of cyclo-oxygenase activity and EDHF all play a role in parasympathetic vasodilatation, but that NO and EDHF are the major endothelium-derived vasodilators in the rat submandibular gland. In addition, when other pathways are blocked EDHF makes a greater contribution in females. Lastly, both vasoactive intestinal peptide and substance P contribute to the atropine-resistant vasodilatation.

Previous studies have shown that submandibular glands suffering interruption of the blood circulation from the main supplying artery have more surviving parenchymal cells in their peripheral portion than in their central portion. Although the reason for this difference between the peripheral and central portions has not yet been clarified, the existence of collateral circulation has been suspected. The present study was designed to examine whether or not the vessels binding the gland proper to the capsule provide such collateral circulation. Silicone rubber or methacrylate was injected into the main artery supplying the mouse submandibular gland, in which the gland proper is wrapped by a capsule similar to that of the human submandibular gland, and then the gland was observed by both stereoscopic and scanning electron microscopy. Three-dimensional observations showed no communicating vessels between the gland proper and the capsule. Therefore, it is suggested that the parenchymal cells surviving in the ischemic peripheral portion of the submandibular gland are nourished by permeation of tissue fluid contained in the capsule.