[Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension].

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

[Implications, spiritual characteristics and practical significance of Chinese schistosomiasis control culture].

The culture of schistosomiasis control is specific in the history of Chinese culture. Broadly speaking, the culture of schistosomiasis control is a summary of specific social mood, social consciousness and material culture created by Chinese populations during the progress of schistosomiasis control since the founding of the People's Republic of China. Narrowly speaking, the culture of schistosomiasis control is the spiritual culture that is jointly created and nurtured by schistosomiasis control workers since the founding of the People's Republic of China. The spiritual features of Chinese schistosomiasis control culture are characterized by the patriotism and care about the people, the matter-to-fact attitude, the pioneering and enterprising spirit, and the spirit of sacrifice and dedication. The ultimate goal of the research on the culture of schistosomiasis control is to facilitate the achievement of the strategic goal of Healthy China 2030 as scheduled, accelerate the progress towards elimination of schistosomiasis, and to promote the sustainable development of schistosomiasis control in China.

[Challenges and countermeasures of schistosomiasis control in Hunan Province in the new era].

This paper describes the current epidemic characteristics and endemic status of schistosomiasis, analyzes the main challenges of schistosomiasis control and proposes the emphasis and interventions for future schistosomiasis control activities in Hunan Province, so as to provide insights into the elimination of schistosomiasis in Hunan Province.

[Application of the exponential smoothing model and ARIMA model in prediction of the endemic situation of schistosomiasis in Hunan Province].

OBJECTIVE: To predict the changes in the prevalence of Schistosoma japonicum infections in humans and livestock in Hunan Province using the exponential smoothing model and the ARIMA model. METHODS: The data pertaining to S. japonicum infections in humans and livestock in Hunan Province from 1957 to 2015 were collected, and the exponential smoothing model and the ARIMA model were created using the software Eviews and PASW Statistics 18.0. In addition, the effectiveness of these two models for the prediction of S. japonicum infections in humans and livestock in Hunan Province from 2016 to 2018 was evaluated. RESULTS: The exponential smoothing model and the ARIMA model had a high goodness of fit for prediction of S. japonicum infections in humans and livestock in Hunan Province from 1957 to 2015. There was a linear trend in the prevalence of S. japonicum infections in humans and livestock in Hunan Province from 1957 to 2015. The prevalence of S. japonicum infections in humans predicted with the Brown's linear trend and the prevalence of S. japonicum infections in livestock predicted with the Holt's linear trend in Hunan Province from 2016 to 2018 fitted better the actual data than the ARIMA model; however, prediction of the ARIMA model indicated that the endemic situation of schistosomiasis remained at a low level in Hunan Province. CONCLUSIONS: At a low epidemic level, development of highly sensitive tools for monitoring schistosomiasis is urgently needed in Hunan Province to fit the current endemic situation, and the schistosomiasis control measures should be intensified to consolidate the control achievements.

[Survey of the capacity building of the county-level schistosomiasis diagnosis network laboratory in Hunan Province].

OBJECTIVE: To examine the construction and operation of the schistosomiasis diagnostic network platform in Hunan Province, so as to provide insights into the improvements of the schistosomiasis diagnostic network laboratory system in the province. METHODS: According to the criteria and requirements for the construction of the county-level schistosomiasis diagnostic network laboratory in China, the establishment and operation of the laboratory were assessed using self-assessment and field review in national schistosomiasis surveillance sites of Hunan Province. RESULTS: A total of 41 county-level schistosomiasis diagnostic network laboratories were built in national schistosomiasis surveillance sites of Hunan Province, and 36 met the requirements for the construction of the national schistosomiasis diagnostic network laboratory in China, which were approved for inclusion in the province-level schistosomiasis diagnostic network laboratory. During the six inter-laboratory comparisons performed by the national schistosomiasis diagnostic reference center of China, full consistency was achieved by 3 county-level schistosomiasis diagnostic network laboratories in Hunan Province, and the coincidence rates for re-review of serological and pathogenic detection samples were 98.40% and 100%, respectively. CONCLUSIONS: The county-level schistosomiasis diagnostic network laboratory system has been preliminarily built and under effective operation in Hunan Province; however, the building capability remains to be improved.

[Endemic situation of schistosomiasis in Hunan Province in 2019].

OBJECTIVE: To analyze the endemic situation of schistosomiasis in Hunan Province in 2019, so as to provide insights into the achievement of transmission interruption of schistosomiasis in the province in 2020. METHODS: The data pertaining to Schistosoma japonicum infections in humans and livestock and snail status were captured from Hunan Province in 2019 and analyzed. RESULTS: Schistosomiasis was endemic in 281 townships (towns) from 41 counties (districts) of 6 cities in Hunan Province by the end of 2019. A total of 991 900 persons received blood testing in Hunan Province in 2019, and 22 773 were positive for the blood testing, with sero-prevalence of 2.30%. All stool examinations were negative in 22 933 individuals detected. The high sero-prevalence was seen in Nanxian County, Anxiang County and Ziyang District. Currently, there were 5 034 cases with advanced schistosomiasis detected in Hunan Province, and they were predominantly identified in Yuanjiang City, Heshan District and Yueyang County. There were 44 963 bovines fenced in schistosomiasis-endemic villages in Hunan Province in 2019, which were predominantly distributed in Yuanjiang City, Hanshou County and Ziyang District, and no positives were detected in 1 996 bovines receiving blood testing or 20 684 bovines receiving stool examinations. In 2019, there were snail habitats of 1.73 billion m2 found in Hunan Province, which were mainly found in Yuanjiang City, Hanshou County and Yueyang County. CONCLUSIONS: The endemic situation of schistosomiasis further decreases in Hunan Province in 2019; however, there is still a risk of schistosomiasis transmission in local areas of the province.

Modified trapdoor procedures by surgical dislocation approach to treat chondroblastoma of the femoral head.

AIMS: The aim of this study was to evaluate the efficacy of the surgical dislocation approach and modified trapdoor procedure for the treatment of chondroblastoma of the femoral head. PATIENTS AND METHODS: A total of 17 patients (ten boys, seven girls; mean age 16.4 years (11 to 26)) diagnosed with chondroblastoma of the femoral head who underwent surgical dislocation of the hip joint, modified trapdoor procedure, curettage, and bone grafting were enrolled in this study and were followed-up for a mean of 35.9 months (12 to 76). Healing and any local recurrence were assessed via clinical and radiological tests. Functional outcome was evaluated using the Musculoskeletal Tumour Society scoring system (MSTS). Patterns of bone destruction were evaluated using the Lodwick classification. Secondary osteoarthritis was classified via radiological analysis following the Kellgren-Lawrence grading system. Steinberg classification was used to evaluate osteonecrosis of the femoral head. RESULTS: The epiphyseal plate was open, closing, and closed in five, five, and seven patients, respectively. In total, eight, six, and three patients were classified as having Lodwick classification IA, IB, and IC, respectively. Allogeneic and autogenous bone grafting was used in 13 and four patients, respectively. All patients had good bone healing and no local recurrence was observed. One patient developed osteonecrosis of the femoral head (Steinberg IA) and one developed secondary osteoarthritis of the hip joint (Kellgren-Lawrence Grade II). The mean postoperative MSTS functional score was 27.7 (24 to 30). CONCLUSION: Surgical dislocation and modified trapdoor procedures are safe and effective techniques for treating chondroblastoma in the femoral head. Cite this article: Bone Joint J 2019;101-B:732-738.

Bovine Mx1 enables resistance against foot-and-mouth disease virus in naturally susceptible cells by inhibiting the replication of viral RNA.

Innate immunity, especially the anti-viral genes, exerts an important barrier function in preventing viral infections. Myxovirus-resistant (Mx) gene take an anti-viral role, whereas its effects on foot-and-mouth disease virus (FMDV) in naturally susceptible cells are still unclear. The bovine primary fetal tracheal epithelial cell line BPTE-siMx1, in which bovine Mx1 gene was silenced, was established and treated with IFN alpha for 6 hr before FMDV infection. The copy numbers of the negative and positive strand viral RNA were determined by strand-specific real-time fluorescence quantitative RT-PCR. The TCID50 of BPTE-siMx1 cells increased at least 17-fold as compared to control cells BPTE-LacZ at 8 hr post infection, thus silencing of bovine Mx1 could promote the replication of FMDV. The amount of both the negative and positive strand viral RNA in BPTE-siMx1 cells significantly increased as compared to BPTE-LacZ cells, indicating that the replication levels of viral RNA were promoted by silencing bovine Mx1. The bovine Mx1 gene could provide resistance against FMDV in the bovine primary fetal tracheal epithelial cells via suppressing the replication of viral RNA.

DNA damage regulates ARID1A stability via SCF ubiquitin ligase in gastric cancer cells.

OBJECTIVE: The gene product of the AT-rich interactive domain 1A (SWI-like) gene (ARID1A) is a member of the SWI/SNF adenosine triphosphate-dependent chromatin-remodeling complexes, which plays an essential role in controlling gene expression and is also involved in cancer development. ARID1A is frequently mutated in a wild variety of cancers and function as a tumor suppressor in several kinds of cancers. ARID1A was down-regulated in gastric cancer, and associated poor patient prognosis. However, how ARID1A protein is regulated in gastric cancer remains largely unknown. MATERIALS AND METHODS: Here, we show that ARID1A protein is rapidly ubiquitinated and degradated in gastric cancer cells in response to DNA damage treatment. RESULTS: Using genetic and pharmacologic Cullin inactivation coupled with in vitro ubiquitination assay, we demonstrate that ARID1A is a substrate of the Cullin-SKP1-F-box protein (SCF) complexes. Moreover, gastric cancer cells with forced expression of ARID1A showed an increased sensitivity to DNA damage reagents. Thus, our data uncovered a previous unknown posttranscriptional regulation of ARID1A by SCF E3 ligase in gastric cancer cells in DNA damage response. CONCLUSIONS: These findings suggest ARID1A might be a promising drug target in gastric cancer treatment.

miR-29 targets Akt3 to reduce proliferation and facilitate differentiation of myoblasts in skeletal muscle development.

MicroRNAs (miRNAs) are a type of endogenous noncoding small RNAs involved in the regulation of multiple biological processes. Recently, miR-29 was found to participate in myogenesis. However, the underlying mechanisms by which miR-29 promotes myogenesis have not been identified. We found here that miR-29 was significantly upregulated with age in postnatal mouse skeletal muscle and during muscle differentiation. Overexpression of miR-29 inhibited mouse C2C12 myoblast proliferation and promoted myotube formation. miR-29 specifically targeted Akt3, a member of the serine/threonine protein kinase family responsive to growth factor cell signaling, to result in its post-transcriptional downregulation. Furthermore, knockdown of Akt3 by siRNA significantly inhibited the proliferation of C2C12 cells, and conversely, overexpression of Akt3 suppressed their differentiation. Collectively and given the inverse endogenous expression pattern of rising miR-29 levels and decreasing Akt3 protein levels with age in mouse skeletal muscle, we propose a novel mechanism in which miR-29 modulates growth and promotes differentiation of skeletal muscle through the post-transcriptional downregulation of Akt3.

Relationship between serum omentin-1 level and bone mineral density in girls with anorexia nervosa.

BACKGROUND: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Omentin- 1, the main circulating adipocytokine, plays an important role in bone metabolism in healthy individuals. However, their association with bone metabolism in AN is unknown. METHODS: Serum omentin-1, bone turnover biochemical markers, and BMD were determined in 26 girls with AN and 24 healthy girls (15-18 years old). RESULTS: Omentin-1 levels increased in AN subjects, and the differences became greater after controlling for fat mass. Omentin-1 was negatively correlated with BMD. In the multiple linear stepwise regression analysis, omentin-1, body mass index and lean mass, but not fat mass, were independent predictors of BMD for the combined group. Significant negative correlations were found between omentin-1 and bone-specific alkaline phosphatase, bone cross-linked N-telopeptides of type I collagen. Omentin-1 was also independently associated with BMD and bone turnover markers in the AN and control groups considered separately. CONCLUSIONS: Omentin-1 was an independent predictor of BMD in adolescents with AN, and negatively correlated with bone turnover markers. This suggested that omentin-1 may exert a negative effect on bone mass by inhibiting bone formation in girls with AN.

Cu fractions, mobility and bioavailability in soil-wheat system after Cu-enriched livestock manure applications.

Fertilization of crops with livestock manure (LM) is a common waste disposal option, but repeated application of LM containing high concentrations of heavy metals such as Cu could lead to crop toxicity and environmental risk. To examine the Cu availability and uptake by wheat in a Mollisol affected by Cu-enriched LM, pot experiments were conducted. LM (376 mg kg⁻¹ Cu originally) was spiked with different concentrations of Cu (0, 100, 200, 400, 600 and 800 mg kg⁻¹ soil, added as CuSO4) to simulate soil Cu contamination by LM application. The results indicated that Cu was predominately distributed in organic bound fraction, while the most drastic increase was found in reducible fraction. Acid-extractable fraction played a more important role than other fractions in controlling the mobility and bioavailability of Cu. DTPA-extractable Cu may overestimate the Cu bioavailability since DTPA solution could extract soluble and part of stable forms. The application of LM at 1% level significantly decline the Cu mobility, but that at 3% level exhibited the opposite effect. Although the quantities of Cu in wheat was very low compared with the accumulation in soil, Cu concentrations in roots increased evidently from 12 to 533 mg kg⁻¹ and that in aerial parts were in a narrow range from 12.1 to 32.7 mg kg⁻¹, indicating the more sensitivity of roots to the Cu toxicity. The Cu concentrations in grains after 3% manure application did not approach the threshold for Cu toxicity (< 20mg kg⁻¹) even at higher Cu addition rates.

Pulmonary selectivity and local pharmacokinetics of ambroxol hydrochloride dry powder inhalation in rat.

The aim of this study was to investigate the local pharmacokinetics and site-specific target efficiency of ambroxol hydrochloride (AH) dry powder inhalation (DPI) by comparing lung epithelial lining fluid (ELF) and plasma AH levels after tracheal administration (TA) with those after intravenous administration. Twelve rats were divided into two groups, one of which was given AH DPI (20 mg/kg) via the trachea and the other was given the same dose AH by intravenous injection (i.v.). Afterwards, each group was subdivided into two groups. The concentration of AH in the ELF was determined by microdialysis in one group while the concentration of AH in plasma was determined in the other group. After AH DPI (20 mg/kg) was given via the trachea, AH achieved a high local concentration in ELF and reached a C(max) at 1.5 h in plasma. After the same dose AH was given by i.v., AH reached a C(max) in ELF at 1.25 h. The (AUC(0-t))(ELF)/(AUC(0-t))(plasma) ratio (1.05-2.25) after TA differed significantly from the ratio (0.029-0.039) observed after intravenous administration (p < 0.05). All these results indicate that AH DPI can be delivered to a specific targeted site and achieve high target efficiency in ELF. DPI could be a useful drug delivery system for AH therapy of pulmonary diseases.

Increased vascular adrenergic vasoconstriction and decreased vasodilation in blacks. Additive mechanisms leading to enhanced vascular reactivity.

Blood pressure reactivity is enhanced in young black subjects through mechanisms that are poorly understood. We compared alpha-adrenergic-mediated vasoconstrictor and ss-adrenergic vasodilator sensitivity and their relation to sympathetic activity in blacks and whites. Ten healthy black (age, 29.9+/-2.4 years) and 10 white (age, 28.3+/-1.9 years) men were studied. Forearm blood flow was measured with strain-gauge plethysmography after the intrabrachial artery administration of phenylephrine (1.25 to 20 microgram/min) and isoproterenol (60 and 400 ng/min) after application of lower-body negative pressure and after a cold pressor test. Forearm and systemic norepinephrine spillover were measured with a radioisotope dilution technique. alpha-Adrenergic vasoconstriction was markedly increased (ANOVA P=0.008) and ss-adrenergic vasodilation decreased (ANOVA P=0.02) in blacks. Phenylephrine (10 microgram/min) decreased forearm blood flow by 58.0+/-2.5% in blacks but only by 26.6+/-6.0% in whites (P<0.001). Vasoconstrictor response to endogenous norepinephrine, stimulated by a cold pressor test, resulted in a higher forearm vascular resistance in blacks than in whites (107.3+/-13 versus 64.8+/-13 mm Hg. mL(-)(1). 100 mL(-)(1), P=0.03). There were no significant ethnic differences in basal or stimulated forearm or systemic norepinephrine spillover. Increased vasoconstrictor and decreased vasodilator responses in blacks were not correlated. Increased sympathetically mediated vascular tone caused by enhanced vasoconstriction and attenuated vasodilation, effects that would be additive, and not increased sympathetic activity could enhance vascular reactivity and may play a role in the pathogenesis of hypertension in blacks.

Effect of Schistosoma japonicum infection on serum testosterone levels in mice.

OBJECTIVE: To determine the effect of Schistosoma japonicum infection on the testoterone level in the sera from male C57BL/6 mice. METHODS: Radioimmunoassay was used to examine testosterone levels in sera of 9 male mice experimentally infected with Schistosoma japonicum. RESULTS: The serum testosterone levels reduced significantly in all experimentally infected animals 45 days after infection, as compared with the uninfected controls. CONCLUSION: Infection with Schistosoma japonicum decreases testosterone levels in the mouse host.

Basal and stimulated sympathetic responses after epinephrine: no evidence of augmented responses.

Delayed facilitation of norepinephrine release through the action of epinephrine (NE) at presynaptic beta-adrenoceptors has been postulated to account for the delayed hemodynamic effects of epinephrine and to be a mechanism causally related to the development of hypertension. To determine whether a short-term increase in epinephrine concentrations resulted in subsequent facilitation of sympathetic responses, 9 healthy subjects (age, 21+/-0.9 years) were studied at rest and during physiological stress on 2 occasions when they received an infusion of either saline or epinephrine (20 ng/kg per minute) in random order. Heart rate, blood pressure, forearm blood flow, epinephrine concentrations, and NE spillover were measured at rest, during mental stress (Stroop test), and during a cold pressor test. Measurements were performed before, during the 1-hour infusion of epinephrine or placebo, and 1 hour after the infusion. A radioisotope dilution method was used to measure NE spillover. Hemodynamic measurements and NE spillover were increased during the infusion of epinephrine, but 1 hour after discontinuation of epinephrine there was no significant augmentation of hemodynamic or sympathetic responses. NE spillover 1 hour after saline or epinephrine infusion was similar (0.85+/-0.2 versus 0. 87+/-0.2 microg/min; P=0.92). In addition, there was no delayed facilitation of stress-induced hemodynamic or NE responses after epinephrine. These findings do not support the hypothesis that epinephrine results in delayed facilitation of NE release.

Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep.

Prostacyclin (or epoprostenol), an arachidonic acid metabolite, is an effective treatment for patients with primary pulmonary hypertension. Interruption of chronic prostacyclin infusion can result in recurrent symptoms of dyspnea and fatigue. The etiology of this phenomenon is unknown. We hypothesized that sympathoadrenal activation could lead to increased vascular tone after abrupt termination of the infusion. To evaluate this effect, we monitored six chronically instrumented, awake sheep during and after infusion of prostacyclin. Prostacyclin decreased mean arterial pressure (MAP) by 14% and increased cardiac output by 33%. After the infusion ceased, MAP rebounded 23% above baseline, and cardiac output decreased by 28% from peak values within 10 min. We were unable to demonstrate an increase in norepinephrine levels after cessation of prostacyclin, nor did alpha-adrenergic blockade affect postinfusion hemodynamics. However, plasma renin activity increased >10-fold at peak infusion and remained elevated for up to 2 h after discontinuation of prostacyclin. Coinfusion of the angiotensin II-receptor antagonist L-158,809 resulted in complete abrogation of the postcessation rise in MAP. We conclude that renin-angiotensin system activation is primarily responsible for systemic hypertension occurring after abrupt cessation of prostacyclin infusion in sheep and that angiotensin II receptor blockade prevents this response. Our data do not support a role for sympathetic nervous system activation in the systemic pressor response after prostacyclin infusion.

Norepinephrine release in the human forearm: effects of epinephrine.

It has been postulated that delayed facilitation of norepinephrine release by epinephrine is causally related to the development of hypertension. It has been proposed that a brief increase in epinephrine concentrations results in the uptake of epinephrine into the sympathetic nerve terminal. Subsequent rerelease of epinephrine stimulates presynaptic beta-adrenergic receptors, resulting in a prolonged increase in plasma norepinephrine (NE) concentrations, with amplified sympathetic responses and vasoconstriction. To determine whether such epinephrine-induced, delayed facilitation of NE release occurs in a vascular bed draining resistance vessels and, if it occurs, whether that facilitation differs in hypertension, we used a radioisotope dilution method to measure unstimulated and isoproterenol-stimulated forearm NE spillover before, during, and after a 50 ng/min infusion of epinephrine for 30 minutes directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normotensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimulated forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus postepinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoproterenol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT preepinephrine 4.04+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We conclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT subjects. Therefore, the prolonged increase in NE concentrations after epinephrine infusion previously shown systemically, and not seen locally in the forearm, suggests that the delayed facilitatory response to epinephrine may occur in other organs.

Sympathoinhibitory response to clonidine is blunted in patients with heart failure.

To determine whether alpha2-adrenergic-mediated sympathoinhibition was altered in chronic heart failure, sympathoinhibitory sensitivity was assessed using the alpha2-adrenergic agonist clonidine in 7 patients with heart failure and in 10 healthy control subjects. Basal norepinephrine spillover was significantly higher in patients with heart failure (1.3+/-0.3 microg/min) than in control subjects (0.7+/-0.1 microg/min, P=.05). Compared with control subjects, the decrement in norepinephrine spillover to cumulative doses of clonidine (1, 2, and 3 microg/kg administered intravenously) was significantly less in patients with heart failure (P<.05). Blood pressure also tended to decrease less in patients with heart failure (P=.06). The doses of clonidine required to produce a 10% decrease in blood pressure and a 25% decrease in norepinephrine spillover were significantly higher in heart failure (P<.01 and P=.05, respectively). Thus, although clonidine lowers norepinephrine spillover significantly in patients with heart failure, such patients are less sensitive to clonidine than healthy control subjects. This difference in sensitivity suggests that doses of clonidine provide effective sympathoinhibition will need to be selected for studies that will evaluate the potential therapeutic effect of clonidine in heart failure.