General Practitioner referrals to Child and Adolescent Mental Health Services: Did they differ during Covid-19?

OBJECTIVES: The COVID pandemic has been associated with poorer mental health in youth. This study aimed to evaluate any change in General Practitioner (GP) referral pattern to Child and Adolescent Mental Health (CAMH) services during the first 10 months of Covid-19 and compare with a similar time frame in 2019. METHODS: All accepted referrals to a CAMH Service in Dublin during the study time frame were reviewed. Referral letters were batch anonymised and clinical data extracted using a study specific proforma for analysis. RESULTS: Referral numbers between the two time periods did not statistically differ. Proportionally more females were referred during the pandemic, increasing to 56.9%, n = 99, compared to 43.1%, n = 75 in 2019 (p = 0.01). Referrals were more often designated by the clinician as urgent during the pandemic (61.3%, n = 98) than before (39%, n = 62, p < 0.001). Referrals outlining self-harm or suicidal ideation increased significantly, from 42.1% (n = 67) to 55.9% (n = 90) (p = 0.014). Referrals for externalising problems fell from 2019 rates; ADHD (21.4%, n = 34 vs 11.1%, n = 18; p = 0.013), ASD (26.4%, n = 42 vs 16.1%, n = 26; p = 0.038) and conduct problems (23.3%, n = 37 vs 7.4%, n = 12; p < 0.001). Although numbers for psychosis in 2019 were low (10.7%, n = 17), these also fell significantly in 2020 (2.5%, n = 4; p < 0.001). DISCUSSION: The finding of reduced referrals for ADHD and ASD has not previously been reported. With concerns regarding educational loss linked to online learning, it is crucial that these youth are not doubly disadvantaged by delayed referral and education decline.

Debut de diabetes tipo 1 en niños durante la pandemia Covid-19 en el Hospital de Pediatría Juan P. Garrahan / Debut of type-1 diabetes in children during the COVID-19 pandemic at Hospital de Pediatría Juan P. Garrahan

Introducción: Según numerosos reportes, la pandemia por COVID­19 aumentó la incidencia de diabetes tipo 1 (DBT1) y cetoacidosis (CAD). Nuestro objetivo fue describir la frecuencia de nuevos casos de DBT1 y su severidad al ingreso en el Hospital J. P. Garrahan durante la pandemia, comparando con el periodo anterior. Material y métodos: Se realizó un estudio descriptivo, observacional, con análisis retrospectivo. Se incluyeron todos los nuevos casos entre 19/03/20- 31/12/21, comparados con el período 19/03/18-31/12/19. El diagnóstico de DBT1, CAD y su severidad se realizó según la International Society for Pediatric and Adolescent Diabetes. Se analizó el requerimiento de cuidados intensivos (UCI), presencia de COVID-19, hemoglobina glicosilada A1C (HbA1C) y autoanticuerpos (GADA, IAA, IA2, ZNT8). Se consideró significativa una p < 0,05. Resultados: En el período 2020-2021 se observó un incremento del 107% de nuevos casos, ingresando 56 pacientes con DBT1. La media y mediana de edad disminuyeron (8 vs 9,1 y 7,7 vs 10,4, respectivamente), con un incremento del 35% de menores de 5 años. Aumentó la frecuencia de CAD severa (41.1% vs 25.9%) y de requerimiento de UCI (17.9% vs 11.1%). La Hb A1C y la glucemia de ingreso mostraron incremento significativo (10.1% vs 12.32%, p<0.003 y 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectivamente). Conclusión: En 2020-2021 se incrementó el número de nuevos casos de DBT1 en nuestra institución. Al ingreso hubo mayor proporción de niños pequeños y casos severos. Las dificultades de acceso a la consulta de atención primaria podrían relacionarse con nuestro hallazgo (AU)

Introduction: Numerous reports have shown that during the COVID-19 pandemic the incidence of type-1 diabetes (T1DB) and ketoacidosis (DKA) increased. The aim of this study was to describe the frequency of new cases and their severity on admission of T1DB at Hospital J. P. Garrahan during the pandemic, compared with the previous period. Material and methods: A descriptive, observational study with a retrospective analysis was conducted. All new cases seen between 19/03/20-31/12/21 were included and compared with the period 19/03/18-31/12/19. The diagnosis of T1DB, DKA, and its severity was made according to the International Society for Pediatric and Adolescent Diabetes. Intensive care (ICU) requirement, presence of COVID-19, glycosylated hemoglobin A1C (HbA1C), and autoantibodies (GADA, IAA, IA2, ZNT8) were analyzed. A p < 0.05 was considered significant. Results: In the period 2020-2021, a 107% increase in new cases was observed including 56 patients with T1DB. Mean and median age decreased (8 vs 9.1 and 7.7 vs 10.4, respectively), with a 35% increase in children under 5 years of age. The frequency of severe DKA (41.1% vs 25.9%) and ICU requirement (17.9% vs 11.1%) increased. Hb A1C and glycemia on admission also showed a significant increase (10.1% vs 12.32%, p<0.003 and 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectively). Conclusion: In 2020-2021 an increase in the number of new cases of T1DB was observed at our institution. On admission, a higher rate of young children and severe cases was found. Difficulties to access primary care may have been related to our finding (AU)

A One Year Cost Analysis of Acute Paediatric Mental Health Presentations.

Aim Examine costs associated with acute mental health presentations (AMHP) to a paediatric emergency department (ED) in 2016 and 2018. Methods Case identification and bed costs were calculated. Results In 2018, 163 youths attended the ED with AMHP, 122 (75%) were admitted (average 8 days), representing a yearly cost to the hospital of €1,028,020, average cost per patient €8,426. This marks an increase of €425,320 or €2,686 per patient compared to 2016. Arriving out of hours, presence of self-harm (SH) and discharge to an inpatient psychiatry bed were all associated with greater costs. Conclusion Despite increasing hospital costs associated with out of hours psychiatric emergencies, dedicated funding is not yet in place. All children should have access to urgent MH assessment. Work force planning and creation of pathways of care for young people with MH needs, including dedicated funding from HSE mental health division must be a priority.

Prevention of Depression in At-Risk Adolescents: Moderators of Long-term Response.

In a randomized controlled trial, we found that a cognitive behavioral program (CBP) was significantly more effective than usual care (UC) in preventing the onset of depressive episodes, although not everyone benefitted from the CBP intervention. The present paper explored this heterogeneity of response. Participants were 316 adolescents (M age = 14.8, SD = 1.4) at risk for depression due to having had a prior depressive episode or having current subsyndromal depressive symptoms and having a parent with a history of depression. Using a recursive partitioning approach to baseline characteristics, we (Weersing et al. 2016) previously had identified distinct risk clusters within conditions that predicted depressive episodes through the end of the continuation phase (month 9). The present study used the same risk clusters that had been derived in the CBP group through month 9 to reclassify the UC group and then to examine group differences in depression through month 33. We found that in this overall very high-risk sample, the CBP program was superior to UC among youth in the low-risk cluster (n = 33), characterized by higher functioning, lower anxiety, and parents not depressed at baseline, but not in the middle (n = 95) and high-risk (n = 25) clusters. Across conditions, significantly more depression-free days were found for youth in the low-risk cluster (M = 951.9, SD = 138.8) as compared to youth in the high-risk cluster (M = 800.5, SD = 226.7). Identification of moderators, based on purely prognostic indices, allows for more efficient use of resources and suggests possible prevention targets so as to increase the power of the intervention.

Paediatric Consultation Liaison Psychiatry Services (PCLPS) -what are they actually doing?

Introduction Paediatric Consultation Liaison Psychiatry Services (PCLPS) are specialised services treating mental health difficulties co-morbid with medical problems. Methods Standardised clinical data was retrieved from all case notes (N=108) during the study timeframe (Jan-June 2016). Results The majority of children were female 59 (55%) with a mean age of 13. Presentation was typically via the Emergency Department (ED) (85, 79%), and of those, the majority (53, 62%) were 'out of hours' and for Deliberate Self-harm (44, 52%) Almost half of all cases seen (50, 46%) were previously known, and discharged back (84, 78%), to CAMHS. Discussion The majority of work conducted by the PCLPS involved children with acute or deteriorating psychiatry disorders, previously known to CAMHS, with a much smaller focus on typical liaison presentations. Adequate resourcing of hospital based PCLPS and 'out of hours' CAMHS are necessary to allow PCLPS provide a specialist service to children with combined medical and MH problems. Given the development of the National Children's Hospital, addressing these resourcing deficits is of vital importance.

The association between economic inactivity and mental health among young people: a longitudinal study of young adults who are not in employment, education or training.

OBJECTIVES: Increasing rates of young people not in education, employment or training (NEETs) are a cause of concern both in Ireland and internationally, but little longitudinal research has examined the link between psychiatric disorder in young people and NEET status. METHODS: The Challenging Times (CT) Study is a longitudinal, population-based study of psychopathology among 212 young Irish people. Clinical interviews were performed at two time points: 12-15 years and 19-24 years. RESULTS: NEET status in young adulthood was associated with a sevenfold increased risk of current suicidal ideation. This result was independent of prior adolescent mental disorder. NEET young people had a fourfold increased odds of being diagnosed with a mental disorder in childhood or early adolescence compared with their economically active peers. NEET young people were at an almost threefold increased risk of any mental health disorder a twofold increased risk of anxiety disorder and threefold increased odds of suicide attempts over their lifetime compared with economically active peers. CONCLUSIONS: NEET young people are at increased risk for mental disorder and suicidal ideation. The association is bidirectional, as prior mental disorder in adolescence appeared to account for much of the association between NEET status and current mental health problems. However, economic inactivity conveys an increased risk for suicidal ideation over and above that due to prior disorder. Our findings provide a compelling economic and societal argument for early intervention and treatment of mental disorder and the importance of vocational interventions for reducing suicide risk in young adults.

Prevalence of Mental Disorder among young adults in Ireland: a population based study.

BACKGROUND: There is a lack of epidemiological research on the mental health of young adults in Ireland. OBJECTIVES: To determine prevalence of psychiatric disorders in a cohort of young Irish adults. METHODS: The Challenging Times study was a landmark study of the prevalence of psychiatric disorders in adolescents in North Dublin, Ireland: 212 school children aged 12-15 years were recruited through schools and interviewed using the K-SADS semi-structured diagnostic instrument. This cohort was traced again at age 19-24 years (mean age 20.8 years) and interviewed using SCID I & II. Main outcome measures were current and lifetime Axis I and Axis II psychiatric disorders. RESULTS: Follow-up rate was 80%. Using a weighted population prevalence analysis 19.8% of the cohort had a current mental disorder, 56.0% had a lifetime mental disorder of whom 28.4% had mood disorders, 27.1% had anxiety disorders, 22.7% had substance use disorders; 25.4% had lifetime multi-morbidity. Cluster A personality disorders were found in 2.3%. Lifetime prevalence of binge-drinking was 75.0%, cannabis use 65% and 17% of young adults had fulfilled criteria for an alcohol use disorder at sometime in their life. Lifetime prevalence of suicidal thoughts/behaviour was 21.1%. CONCLUSIONS: Lifetime prevalence of psychiatric disorder and substance use were high in this sample of young Irish adults. Mental Health service provision for this age group is a priority. Larger studies of nationally representative samples are needed to inform service development.

Methodological considerations in service use assessment for children and youth with mental health conditions; issues for economic evaluation.

Economic evaluations are increasingly used in decision-making. Accurate measurement of service use is critical to economic evaluation. This qualitative study, based on expert interviews, aims to identify best approaches to service use measurement for child mental health conditions, and to identify problems in current methods. Results suggest considerable agreement on strengths (e.g., availability of accurate instruments to measure service use) and weaknesses, (e.g., lack of unit prices for services outside the health sector) or alternative approaches to service use measurement. Experts also identified some unresolved problems, for example the lack of uniform definitions for some mental health services.

Immunological biomarkers: catalysts for translational advances in autoimmune diabetes.

In a recent workshop organized by the JDRF focused on the 'Identification and Utilization of Robust Biomarkers in Type1 Diabetes', leaders in the field of type 1 diabetes (T1D)/autoimmunity and assay technology came together from academia, government and industry to assess the current state of the field, evaluate available resources/technologies and identify gaps that need to be filled for moving the field of T1D research forward. The highlights of this workshop are discussed in this paper, as well as the proposal for a larger, planned consortium effort, incorporating a JDRF Biomarker Core, to foster collaboration and accelerate progress in this critically needed area of T1D research.

Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.

AIMS/HYPOTHESIS: Type 1 diabetes results from a chronic autoimmune process continuing for years after presentation. We tested whether treatment with teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes. METHODS: In a randomised placebo-controlled trial we treated 58 participants with type 1 diabetes for 4-12 months with teplizumab or placebo at four academic centres in the USA. A central randomisation centre used computer generated tables to allocate treatments. Investigators, patients, and caregivers were blinded to group assignment. The primary outcome was a comparison of C-peptide responses to a mixed meal after 1 year. We explored modification of treatment effects in subgroups of patients. RESULTS: Thirty-four and 29 subjects were randomized to the drug and placebo treated groups, respectively. Thirty-one and 27, respectively, were analysed. Although the primary outcome analysis showed a 21.7% higher C-peptide response in the teplizumab-treated group (0.45 vs 0.371; difference, 0.059 [95% CI 0.006, 0.115] nmol/l) (p = 0.03), when corrected for baseline imbalances in HbA(1c) levels, the C-peptide levels in the teplizumab-treated group were 17.7% higher (0.44 vs 0.378; difference, 0.049 [95% CI 0, 0.108] nmol/l, p = 0.09). A greater proportion of placebo-treated participants lost detectable C-peptide responses at 12 months (p = 0.03). The teplizumab group required less exogenous insulin (p < 0.001) but treatment differences in HbA(1c) levels were not observed. Teplizumab was well tolerated. A subgroup analysis showed that treatment benefits were larger in younger individuals and those with HbA(1c) <6.5% at entry. Clinical responders to teplizumab had an increase in circulating CD8 central memory cells 2 months after enrolment compared with non-responders. CONCLUSIONS/INTERPRETATIONS: This study suggests that deterioration in insulin secretion may be affected by immune therapy with teplizumab after the new-onset period but the magnitude of the effect is less than during the new-onset period. Our studies identify characteristics of patients most likely to respond to this immune therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00378508 FUNDING: This work was supported by grants 2007-502, 2007-1059 and 2006-351 from the JDRF and grants R01 DK057846, P30 DK20495, UL1 RR024139, UL1RR025780, UL1 RR024131 and UL1 RR024134 from the NIH.

Cyberbullying and its effects on young adolescents: a community-based survey.

OBJECTIVES: To conduct a study looking at the prevalence and nature of Internet and mobile phone use in young people, focusing particularly on cyberbullying and its potential effects on young people's mental health. METHOD: Three secondary schools in an area of North Dublin were randomly selected, which included one all boys school, one all girls school and one co-educational school. Written information about the study was given to each school principal and to parents/carers of all first and second year students. First and second year students in each school from whom consent had been received were asked to complete two questionnaires, which included a questionnaire on cyberbullying and a self-report version of the Strengths and Difficulties Questionnaire (SDQ). A total of 130 students completed the study. RESULTS: A total of 24 (18.46%) pupils were cyberbullied. Of these, 13 (65% of those cyberbullied) pupils who were cyberbullied said that it had a negative effect on their mood, and 9 (45% of those cyberbullied) said that cyberbullying had a negative effect on their overall mental health. A statistically significant higher proportion of pupils who were cyberbullied scored in the Abnormal/Borderline range of the SDQ, compared with those who were not cyberbullied. CONCLUSION: This is the first study in Ireland, which looks at the potential mental health difficulties associated with cyberbullying. It is hoped that the information from this study will help to increase awareness of the effects of cyberbullying and help look at ways of managing cyberbullying.

Relapsing and remitting severe hypoglycemia due to a monoclonal anti-insulin antibody heralding a case of multiple myeloma.

CONTEXT: We report a novel case of insulin autoimmune syndrome (IAS) presenting with hypoglycemia due to production of a monoclonal anti-insulin antibody in a patient subsequently found to have multiple myeloma (MM). OBJECTIVE: The aim of the study was to describe the 5-yr clinical course of a patient with IAS and MM and to characterize the origin and function of the pathogenic antibody. METHODS: We conducted a longitudinal case history with laboratory investigations to characterize the anti-insulin antibody subtype, specificity, affinity, and origin. RESULTS: The patient presented with IAS, which worsened during treatment of hepatitis C. The patient was then discovered to have a monoclonal gammopathy that progressed to MM. Treatment of the MM induced remission of the neoplasia and IAS, which then followed a synchronized course of progression and response to therapy. An anti-insulin IgG(3)-λ that bound specifically but with low affinity to the insulin B chain (amino acids 9-30) and that was distinct from the primary MM IgG(3)-κ clone was recovered from the patient and cloned. The antibody bound insulin and showed mutations of normal affinity maturation. CONCLUSIONS: We describe a case of MM heralded by IAS, where full characterization of the pathogenic antibody revealed that the monoclonal anti-insulin antibody had originated from a self-reactive clone.

Analysis of human biologics with a mouse skin transplant model in humanized mice.

Preclinical testing of human therapeutic monoclonal antibodies has been limited in murine models due to species differences in pharmacokinetics and biologic responses. To overcome these constraints we developed a murine skin transplant model in humanized mice and used it to test human monoclonal antibody therapy. Neonatal NOD/SCID/IL2Rγc(null) mice (NSG) were reconstituted with human CD34(+) hematopoietic stem cells (hNSG). When adult, these mice rejected MHC mismatched murine C57BL/6J skin grafts. Rejection required adequate reconstitution with human cells. There was diffuse infiltration of the epidermis and dermis with hCD8 and hCD4 cells in rejected grafts by immunohistochemistry. Studies with B6/MHC class I and II knockout mice donors indicated that neither is required for rejection. Graft rejection was associated with the development of effector and central memory T cells and an increase in serum immunoglobulins. We also tested the effects of teplizumab (anti-CD3 mAb) and found it could delay skin graft rejection, whereas ipilimumab (anti-CTLA-4 [cytotoxic T-lymphocyte antigen-4] mAb) treatment accelerated rejection. These findings demonstrate that hNSG mice reliably and predictably reject a xenogenic mouse skin graft by a human T cell mediated mechanism. The model can be utilized to investigate the ability of human immunotherapies to enhance or suppress functional human immune responses.

Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence.

BACKGROUND: Adolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence. METHOD: Psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) semi-structured instrument were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about early traumatic events, cannabis use and psychiatric symptoms in adolescence. RESULTS: In separate analyses both cannabis use and childhood trauma were significantly associated with risk of experiencing psychotic symptoms. However, the presence of both childhood trauma and early cannabis use significantly increased the risk for psychotic symptoms beyond the risk posed by either risk factor alone, indicating that there was a greater than additive interaction between childhood trauma and cannabis use. CONCLUSION: Our finding of a greater than additive interaction between childhood trauma and cannabis use may have implications for the identification of individuals at high risk of experiencing psychotic symptoms. For example, measures to actively discourage or intensively treat cannabis use in children and adolescents who have experienced abuse may help to prevent the development of psychosis in this vulnerable group. Our findings require replication in larger samples to confirm this interaction effect.

High bone turnover in Irish professional jockeys.

SUMMARY: Professional jockeys are routinely exposed to high impact trauma and sustain fractures frequently. We found that jockeys restrict their caloric intake in order to maintain regulation weights, and that bone turnover is high. There are significant health and safety implications for the racing industry. INTRODUCTION: Professional jockeys routinely sustain fractures from high impact falls. Jockeys maintain a low percentage body fat and a low body mass index (BMI) to achieve low weight targets in order to race. We evaluated dietary habits and bone metabolism in jockeys. METHODS: Bone mineral density (BMD) was measured in 27 male jockeys of the 144 jockeys licensed in Ireland. Fourteen (52%) had BMD T score below -1.0, of whom 12 consented to clinical review, nutritional survey, endocrine studies, and bone turnover markers (BTM). BTM were compared to age- and sex-matched controls (n = 16). RESULTS: BMI was 20.6 +/- 1.7 kg/m(2); previous fracture frequency was 3.2 +/- 2.0 per rider. All had normal endocrine axes. The jockeys' diet as determined by a 7-day dietary recall was deficient in energy, calcium, and vitamin D intake. Compared with the control group, the jockey group had evidence of increased bone turnover. CONCLUSIONS: A substantial proportion of the professional jockeys in Ireland have low-normal BMD, low BMI, and high bone turnover that may result from weight and dietary restrictions. These factors seem to have a deleterious effect on their bone health and predispose the jockeys to a high fracture risk that should be remediated.

Dress and address: patient preferences regarding doctor's style of dress and patient interaction.

We sought to determine patient preferences regarding doctor's dress styles and mode of doctors introducing themselves to patients and addressing patients. A survey of patients attending a general medical/endocrinology outpatient clinic in a tertiary referral hospital over a 6 week period was performed. 124 people completed the survey (62 male, 62 female). Mean age was 52.3 years (Range 19-84). Patients preferred to be addressed by their first name while they prefer doctors to introduce themselves by their first and last name. However the majority of patients found all forms of doctors introducing themselves acceptable. Patients preferred formal attire for both male and female doctors, with a white coat being the most preferred option. 84.5% of patients felt that doctors should wear name badges in a clearly visible place although only 26% of patients saw name badges always or almost always during a consultation. This study raises important points regarding the doctor patient interaction.

Health services use in eating disorders.

BACKGROUND: This study examined healthcare services used by adults diagnosed with an eating disorder (ED) in a large health maintenance organization in the Pacific Northwest. METHOD: Electronic medical records were used to collect information on all out-patient and in-patient visits and medication dispenses, from 2002 to 2004, for adults aged 18-55 years who received an ED diagnosis during 2003. Healthcare services received the year prior to, and following, the receipt of an ED diagnosis were examined. Cases were matched to five comparison health plan members who had a health plan visit close to the date of the matched case's ED diagnosis. RESULTS: Incidence of EDs (0.32% of the 104,130 females, and 0.02% of the 93,628 males) was consistent with prior research employing treatment-based databases, though less than community-based samples. Most cases (50%) were first identified during a primary-care visit and psychiatric co-morbidity was high. Health services use was significantly elevated in all service sectors among those with an ED when compared with matched controls both in the year preceding and that following the receipt of the incident ED diagnosis. Contrary to expectations, healthcare utilization was found to be similarly high across the spectrum of EDs (anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified). CONCLUSIONS: The elevation in health service use among women both before and after diagnosis suggests that EDs merit identification and treatment efforts commensurate with other mental health disorders (e.g. depression) which have similar healthcare impact.

When a stroke is not a stroke; posterior leukoencephalopathy syndrome mimicking posterior circulation stroke.

Posterior leukoencephalopathy syndrome (PLS) is a potentially reversible syndrome that may mimic the clinical and radiological features of posterior circulation cerebral infarction. Three cases of PLS are presented which were erroneously diagnosed as strokes and treated in accordance with recent evidence based guidelines; none of the cases fulfilled the current criteria requiring treatment for hypertension in the acute stroke setting. Once the diagnosis of PLS was made, and the patients blood pressure treated aggressively, all patients had rapid and full clinical resolution of their symptoms. Given the important differences in management and prognosis, rapid and accurate diagnosis is essential. Posterior leukoencephalopathy syndrome needs to be considered in patients presenting with clinical and/or radiological findings that predominantly affect the occipital lobes.

Adenosine and hypoxic dilation of rat coronary small arteries: roles of the ATP-sensitive potassium channel, endothelium, and nitric oxide.

The aims of the study were to examine the roles of the ATP-sensitive potassium (K(ATP)) channel, the endothelium, and nitric oxide (NO) in the responses of rat coronary small arteries to adenosine and hypoxia. Segments of rat coronary vessel were investigated in vitro using pressure myography; all vessels studied developed stable spontaneous myogenic tone during equilibration. Glibenclamide (a K(ATP) channel inhibitor) reversed pinacidil but not 2-deoxyglucose-induced dilation. Both adenosine and hypoxia dilated the vessels, and glibenclamide did not reverse these responses. Endothelial removal or N(G)-nitro-L-arginine methyl ester (L-NAME) inhibited the dilation to adenosine by approximately 50%; subsequent addition of glibenclamide was without effect. Hypoxic dilation was completely inhibited by endothelium removal or L-NAME. We conclude that adenosine- and hypoxia-induced dilation of rat coronary arteries does not appear to involve the K(ATP) channel. Adenosine-induced dilation is partially and hypoxic dilation is completely dependent on endothelium-derived NO.