Associations of a family history of lupus with the risks of lupus and major psychiatric disorders in first-degree relatives.

BACKGROUND: Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. AIM: We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. DESIGN AND METHODS: Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. RESULTS: The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. CONCLUSIONS: The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.

GAD65 as a potential marker for cognitive performance in an adult population with prediabetes.

BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for cognitive dysfunction in aged populations. However, there are inconsistent reports about impaired fasting glucose or prediabetes as an independent risk factor for cognitive function. Glutamic acid decarboxylase 65 (GAD65) is the key enzyme responsible for γ-aminobutyric acid synthesis in the central nervous system. Antibodies against GAD65 (GAD65Abs) are not only detected in approximately 80% of early-onset type 1 DM, but also linked to several neurological disorders. AIM: This study aims to investigate the association between GAD65Ab titer levels and cognitive performance. In addition, we assessed the effect of GAD65Ab on cognitive function in adults with normal fasting glucose, prediabetes and DM. METHODS: A total of 328 subjects aged 49.10 ± 5.72 years were enrolled from the Third Health and Nutrition Examination Survey dataset. Cognitive performance was assessed by three computerized neurobehavioral tests, including the serial digit learning test, simple reaction time test (SRTT) and symbol-digit substitution test (SDST). RESULTS: Subjects with higher GAD65Ab titers had significantly poorer cognitive function in the SRTT and SDST (P < 0.05). Additionally, GAD65Ab was associated with cognitive decline in non-diabetic adults after adjusting for a number of relevant variables (P < 0.05 in both SRTT and SDST). CONCLUSIONS: These results indicate that GAD65Ab may be a potential marker for cognitive impairment in non-diabetic adults.

Prevention of Postdental Procedure Bacteremia: A Network Meta-analysis.

Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.

In-hospital mortality among electroconvulsive therapy recipients: A 17-year nationwide population-based retrospective study.

BACKGROUND: Electroconvulsive therapy (ECT) remains irreplaceable in the treatment of several psychiatric conditions. However, evidence derived using data from a national database to support its safety is limited. The aim of this study was to investigate in-hospital mortality among patients with psychiatric conditions treated with and without ECT. METHODS: Using data from the Taiwan National Health Insurance Research Database from 1997 to 2013, we identified 828,899 inpatients with psychiatric conditions, among whom 0.19% (n=1571) were treated with ECT. RESULTS: We found that ECT recipients were more frequently women, were younger and physically healthier, lived in more urbanized areas, were treated in medical centers, and had longer hospital stays. ECT recipients had lower odds of in-hospital mortality than did those who did not receive ECT. Moreover, no factor was identified as being able to predict mortality in patients who underwent ECT. Among all patients, ECT was not associated with in-hospital mortality after controlling for potential confounders. CONCLUSION: ECT was indicated to be safe and did not increase the odds of in-hospital mortality. However, ECT appeared to be administered only on physically healthy but psychiatrically compromised patients, a pattern that is in opposition with the scientific evidence supporting its safety. Moreover, our data suggest that ECT is still used as a treatment of last resort in the era of modern psychiatry.

Association between monoamine oxidase B A644G polymorphism and Parkinson's disease risk: a meta-analysis in the Chinese population.

Although various individual studies have evaluated the correlation between monoamine oxidase B (MAOB), polymorphism, and Parkinson's disease (PD), the results remain inconclusive. Therefore, we performed a meta-analysis in the Chinese population to provide comprehensive data on the association between the MAOB polymorphism and PD. Eligible studies were identified via databases such as PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine, throughout November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strengths of these associations. Eight studies documenting a total of 1385 cases of PD and 1426 controls were included in this meta-analysis. Overall, no significant association was found between the MAOB A644G polymorphism and PD risk in the Chinese population. However, in subgroup analyses, where results were stratified by geographical areas and source of controls, increased risk for PD in Northern China was observed (allele A vs G: OR = 1.33, 95%CI = 1.11-1.58; AA vs GG: OR = 1.46, 95%CI = 1.09-1.97; AA + AG vs GG: OR = 1.42, 95%CI = 1.06-1.90). Similarly, population-based studies also showed significant association between the MAOB A644G polymorphism and PD risk among different populations (allele A vs G: OR = 1.29, 95%CI = 1.11-1.51; AA vs GG: OR = 1.41, 95%CI = 1.09-1.82; AA + AG vs GG: OR = 1.34, 95%CI = 1.04- 1.71). In conclusion, this meta-analysis provided evidence that the MAOB A644G polymorphism may contribute to PD development in Northern China. Further studies conducted in other ethnic groups are required for definite conclusions.

[A multicenter study on the prognostic factors of one year outcomes in patients with poor grade intracranial aneurysm after early treatment].

OBJECTIVES: To explore the one year outcome of subarachnoid hemorrhage (SAH) patients with poor grade intracranial aneurysm who underwent early treatment (within 72 hours), and to analyze the possible predictors of the prognosis. METHODS: This clinical study was a prospective, multicenter, observational registry of SAH patients with poor grade intracranial aneurysm. Data pertaining to 203 SAH patients with poor grade intracranial aneurysm between October 2010 and March 2013 from 10 medical centers. There were 100 male and 103 female patients. Neurological outcomes at 12 months after the surgery were measured using the Glasgow Outcome Scale (GOS). Genders, age, smoke, breath, herniation, aneurysm location, World Federation of Neurosurgical Societies (WFNS) grade, CT Fisher's grade, alcohol consumption, aneurysm diameter, surgical procedure and operation time were identified as possible prognostic factors, the association between possible prognostic factors and outcome were analyzed, using univariate and multivariate analysis. Univariate analysis included Wilcoxon rank sum test, Kruskal-Wallis H test and Nemenyi test, multivariate analysis included Logistic regression test. RESULTS: Among 203 patients, 94 patients were WFNS grade Ⅳ, and 109 patients were WFNS grade Ⅴ; 31 patients were CT Fisher's grade 1 to 2, 172 patients were CT Fisher's grade 3 to 5. Herniation (OR=2.535, 95%CI: 1.204 to 5.339, P=0.014), WFNS grade Ⅴ (OR=3.728, 95%CI: 1.972 to 7.043, P=0.000), CT Fisher's grade 3 to 5 (OR=5.641, 95%CI: 2.032 to 15.643, P=0.001), and anterior circulation location (OR=6.234, 95%CI: 1.996 to 19.472, P=0.002) were found to be independent prognostic factors of unfavorable prognosis. CONCLUSIONS: Early surgical treatment could improve the prognosis of SAH patients with poor-grade-aneurysm. The patients with herniation, WFNS grade Ⅴ, CT Fisher's grade 3 to 5, anterior circulation aneurysms suffered unfavorable prognosis.

Continuing weight-loss effect after topiramate discontinuation in obese persons with schizophrenia: a pilot open-label study.

INTRODUCTION: Few studies have investigated the likelihood of weight maintenance in obese persons with schizophrenia after their initial successful weight loss. This pilot open-label study examined the efficacy of topiramate in weight loss and the trajectory of weight changes after topiramate discontinuation. METHODS: This study enrolled 10 obese persons with schizophrenia. A 4-month treatment phase was started, followed by a 12-month discontinuation phase. Body weight was measured as the primary outcome every month. Secondary outcomes included leptin levels, fasting glucose, lipid profiles, and insulin resistance index. RESULTS: After the 4-month addition of topiramate, participants lost 1.79 kg of their body weight (95% CI=-3.03 to -0.56, p=0.005). The maximum weight reduction was 4.32 kg, occurring when topiramate had been discontinued for 12 months (95% CI=-6.41 to -2.24, p<0.001). DISCUSSION: The continuing weight-loss effect after topiramate discontinuation might have resulted from topiramate's potential to improve leptin functioning. These findings demonstrate that topiramate's weight-loss effect could not only persist during its administration, but also continue to improve after its discontinuation.

An unusual presentation of catatonia in a patient with schizoaffective disorder.

Catatonia is currently a diagnosis that is made clinically; however, due to the varied clinical presentations of catatonia, underdiagnosis is common. We describe an unusual presentation of catatonia in a female patient with schizoaffective disorder. She was successfully treated, albeit with a significant delay. Among an extensive series of laboratory tests and treatment trials, serum levels of D-dimer were elevated during the illness and relieved with recovery.

Antioxidant vitamins prevent cardiomyocyte apoptosis produced by norepinephrine infusion in ferrets.

BACKGROUND: Norepinephrine (NE) induces apoptosis in cultured neonatal rat myocytes. To determine whether this change occurred in intact animals after chronic subhypertensive doses of NE, and whether the effect was mediated via oxidative stress produced by NE, we measured myocyte apoptosis and apoptotic gene proteins in ferrets receiving chronic NE with and without antioxidant vitamin treatment. METHODS: Ferrets were administered either subcutaneous NE or vehicle and simultaneously assigned to receive antioxidant vitamins (beta-carotene, ascorbic acid and alpha-tocopherol) or vehicle for 4 weeks. Resting hemodynamics and plasma NE were measured at 4 weeks. Animals were then sacrificed for measuring cardiac myocyte size by electron microscopy, and oxidative stress by reduced to oxidized glutathione (GSH/GSSG) ratio and mitochrondrial DNA 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). Cardiomyocyte apoptosis was detected by both terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and monoclonal antibody to single-stranded DNA (Mab) staining. Western blot analysis was used to measure the expression of the antiapoptotic protein Bcl-2 and apoptotic protein Bax. RESULTS: NE administration produced a 4-fold increase in plasma NE, but had no effect on resting heart rate, heart weight, arterial pressure, left ventricular systolic function or cardiac cell size. NE infusion decreased tissue GSH/GSSG ratio, and increased mtDNA 8-oxo-dG, and TUNEL- and Mab-positive apoptotic cells. These changes were associated with a 27% decrease in Bcl-2 protein, a 42% increase in Bax and a 57% reduction in the ratio of Bcl-2/Bax. All of the changes were prevented by co-administration of antioxidant vitamins. CONCLUSION: NE administration at a dose which produced no significant increase in blood pressure or myocyte hypertrophy caused cardiomyocyte apoptosis in intact animals. This effect was associated with an increase in oxidative stress, up-regulation of Bax protein and down-regulation of Bcl-2 protein. Antioxidant vitamins prevented the changes produced by NE. The findings suggest that NE-induced myocyte apoptosis is mediated by oxidative stress, and that antioxidant vitamins may be beneficial in heart failure in which cardiac NE release is increased.

Significance of glutamate and dopamine neurons in the ventral pallidum in the expression of behavioral sensitization to amphetamine.

To explore the significance of ventral pallidum (VP) during the amphetamine sensitization, we first investigated if there are neurochemical alterations in the VP during amphetamine withdrawal period. Chronic amphetamine-treated (5 mg/kg x 14 days) rats displayed an apparent locomotion sensitization as compared with saline controls when challenged with 2 mg/kg amphetamine at withdrawal days 10-14. A microdialysis analysis revealed that output of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the VP of amphetamine-sensitized rats increased approximately two-fold as compared to controls at both pre- and post-amphetamine challenge period. On the other hand, the in vivo glutamate output in the VP increased upon amphetamine challenge in the behaviorally sensitized rats, but not in the controls. To evaluate if drug manipulation in the VP would affect the behavioral sensitization, we treated both groups of rats with NMDA receptor antagonist, MK-801 (5 microg/microl for 5 days; bilateral) in the VP during withdrawal days 6-10. Animals were challenged with 2 mg/kg amphetamine at withdrawal day 11. The behavioral profile exhibited that MK-801 pre-treatment significantly blocked the locomotion hyperactivity in amphetamine-sensitized rats. Taken together, the current results suggest that the excitatory amino acid in the VP plays a significant role during the expression of behavioral sensitization to amphetamine.

Renin-angiotensin system inhibition on noradrenergic nerve terminal function in pacing-induced heart failure.

Chronic angiotensin-converting enzyme (ACE) inhibition has been shown to improve cardiac sympathetic nerve terminal function in heart failure. To determine whether similar effects could be produced by angiotensin II AT(1) receptor blockade, we administered the ACE inhibitor quinapril, angiotensin II AT(1) receptor blocker losartan, or both agents together, to rabbits with pacing-induced heart failure. Chronic rapid pacing produced left ventricular dilation and decline of fractional shortening, increased plasma norepinephrine (NE), and caused reductions of myocardial NE uptake activity, NE histofluorescence profile, and tyrosine hydroxylase immunostained profile. Administration of quinapril or losartan retarded the progression of left ventricular dysfunction and attenuated cardiac sympathetic nerve terminal abnormalities in heart failure. Quinapril and losartan together produced greater effects than either agent alone. The effect of renin-angiotensin system inhibition on improvement of left ventricular function and remodeling, however, was not sustained. Our results suggest that the effects of ACE inhibitors are mediated via the reduction of angiotensin II and that angiotensin II plays a pivotal role in modulating cardiac sympathetic nerve terminal function during development of heart failure. The combined effect of ACE inhibition and angiotensin II AT(1) receptor blockade on cardiac sympathetic nerve terminal dysfunction may contribute to the beneficial effects on cardiac function in heart failure.

Selegiline improves cardiac sympathetic terminal function and beta-adrenergic responsiveness in heart failure.

Selegiline is a centrally acting sympatholytic agent with neuroprotective properties. It also has been shown to promote sympathetic reinnervation after sympathectomy. These actions of selegiline may be beneficial in heart failure that is characterized by increased sympathetic nervous activity and functional sympathetic denervation. Twenty-seven rabbits with rapid cardiac pacing (360 beats/min, 8 wk) and twenty-three rabbits without pacing were randomly assigned to receive selegiline (1 mg/day, 8 wk) or placebo. Rapid pacing increased plasma norepinephrine (NE) and decreased left ventricular fractional shortening, baroreflex sensitivity, cardiac sympathetic nerve terminal profiles, cardiac NE uptake activity, and myocardial beta-adrenoceptor density. Selegiline administration to animals with rapid ventricular pacing attenuated the increase in plasma NE and decreases in fractional shortening, baroreflex sensitivity, sympathetic nerve profiles, NE uptake activity and beta-adrenoceptor density. Thus selegiline appears to exert a sympatholytic and cardiac neuroprotective effect in pacing-induced cardiomyopathy. The effects are potentially beneficial because selegiline not only improves cardiac function but also increases baroreflex sensitivity in heart failure.

Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group.

BACKGROUND: Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. We investigated the clinical use of nesiritide in such patients. METHODS: Patients hospitalized because of symptomatic congestive heart failure were enrolled in either an efficacy trial or a comparative trial. In the efficacy trial, which required the placement of a Swan-Ganz catheter, 127 patients with a pulmonary-capillary wedge pressure of 18 mm Hg or higher and a cardiac index of 2.7 liters per minute per square meter of body-surface area or less were randomly assigned to double-blind treatment with placebo or nesiritide (infused at a rate of 0.015 or 0.030 microg per kilogram of body weight per minute) for six hours. In the comparative trial, which did not require hemodynamic monitoring, 305 patients were randomly assigned to open-label therapy with standard agents or nesiritide for up to seven days. RESULTS: In the efficacy trial, at six hours, nesiritide infusion at rates of 0.015 and 0.030 microg per kilogram per minute decreased pulmonary-capillary wedge pressure by 6.0 and 9.6 mm Hg, respectively (as compared with an increase of 2.0 mm Hg with placebo, P<0.001), resulted in improvements in global clinical status in 60 percent and 67 percent of the patients (as compared with 14 percent of those receiving placebo, P<0.001), reduced dyspnea in 57 percent and 53 percent of the patients (as compared with 12 percent of those receiving placebo, P<0.001), and reduced fatigue in 32 percent and 38 percent of the patients (as compared with 5 percent of those receiving placebo, P<0.001). In the comparative trial, the improvements in global clinical status, dyspnea, and fatigue were sustained with nesiritide therapy for up to seven days and were similar to those observed with standard intravenous therapy for heart failure. The most common side effect was dose-related hypotension, which was usually asymptomatic. CONCLUSIONS: In patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Nesiritide is useful for the treatment of decompensated congestive heart failure.

Alterations in cardiac adrenergic terminal function and beta-adrenoceptor density in pacing-induced heart failure.

Congestive heart failure is associated with cardiac adrenergic nerve terminal changes and beta-adrenoceptor density downregulation. To study the temporal sequence of these changes, we performed studies in rabbits at 2, 4, and 8 wk of cardiac pacing (360 beats/min) and at 1, 2, and 4 wk after cessation of pacing. Rapid pacing produced left ventricular (LV) dysfunction and an increase in plasma norepinephrine (NE) in 1-2 wk. At week 2, NE uptake activity, NE uptake-1 density, and adenylyl cyclase responses to isoproterenol, 5'-guanylyl imidodiphosphate [Gpp(NH)p], and forskolin reduced. However, immunostained tyrosine hydroxylase profile, beta-adrenoceptor density, and NE histofluorescence did not reduce until 4-8 wk of pacing. After cessation of cardiac pacing, LV function normalized quickly, followed by return of tyrosine hydroxylase and NE profiles in 1 wk and adenylyl cyclase responses to agonists and NE uptake activity in 2 wk. Myocardial beta-adrenoceptor density returned to normal by 4 wk after cessation of pacing. Our results suggest that there is no permanent structural neuronal damage in the myocardium within the first 8 wk of rapid cardiac pacing. Abnormal myocardial NE reuptake mechanism may play an important pathophysiological role in heart failure.

Myocardial beta-adrenoceptor down-regulation by norepinephrine is linked to reduced norepinephrine uptake activity.

Chronic administration of norepinephrine for 8 weeks has been shown to reduce neuronal norepinephrine uptake activity and increase interstitial norepinephrine concentration in the heart. To determine whether the changes could lead to myocardial beta-adrenoceptor down-regulation or beta-adrenergic subsensitivity, we measured left ventricular contractile responses to dobutamine, myocardial beta-adrenoceptor density, beta subtype distribution, competitive inhibition agonist binding, and adenylyl cyclase activity activation by isoproterenol, 5'-guanylylimidodiphosphate, and forskolin in dogs after a norepinephrine or saline infusion for 8 weeks. We found that norepinephrine infusion reduced myocardial beta-adrenoceptor density, beta(1)-adrenoceptor subtype density, and high-affinity site for isoproterenol. Left ventricular contractile responses to dobutamine were reduced in the norepinephrine-infused animals. In addition, norepinephrine infusion decreased the basal adenylyl cyclase activity and the adenylyl cyclase responses to isoproterenol, 5'-guanylylimidodiphosphate, and forskolin. The findings indicate that a decrease in cardiac norepinephrine uptake predisposes the heart to norepinephrine-induced myocardial beta-adrenoceptor down-regulation, and that norepinephrine, when present in a sufficient amount over a long period as it is in chronic heart failure, can reduce myocardial beta-adrenergic responsiveness by both homologous and heterologous desensitization.

ACE inhibition improves cardiac NE uptake and attenuates sympathetic nerve terminal abnormalities in heart failure.

Cardiac sympathetic nerve terminal dysfunction plays an important role in the downregulation of myocardial beta-adrenoceptors in heart failure. To determine whether chronic angiotensin-converting enzyme (ACE) inhibition improved cardiac sympathetic nerve terminal function and hence increased myocardial beta-adrenergic responsiveness, we administered ACE inhibitors to dogs with chronic right-sided heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. The RHF animals exhibited fluid retention, elevated right heart filling pressures, blunted inotropic response to isoproterenol, and reduced beta-adrenoceptor density. These changes were accompanied by decreases in right ventricular norepinephrine (NE) uptake and neuronal NE histofluorescence and tyrosine hydroxylase immunoreactive profiles. ACE inhibitors had no effect on the production of heart failure but greatly reduced the attenuation of cardiac NE uptake, neuronal NE histofluorescence, and tyrosine hydroxylase immunoreactive profiles. ACE inhibition also improved the inotropic response to isoproterenol and restored myocardial beta-adrenoceptor density. The changes probably are caused by reduction of cardiac NE release by ACE inhibition and may contribute to the beneficial effects of ACE inhibitor therapy in patients with chronic heart failure.

Chamber-specific regulation of heme oxygenase-1 (heat shock protein 32) in right-sided congestive heart failure.

Heme oxygenase (HO)-1 is a stress protein (HSP 32) and, together with HO-2, catalyses oxidation of the heme molecule to generate carbon monoxide, a gas with vasodilatory properties, and bilirubin, an antioxidant. Right-sided heart failure (RHF) resulted in a two-fold increase in the HO-1 transcript (;1.8 kb) in the right ventricle (RV) of RHF dogs compared to that of controls. In contrast, the left ventricle showed no increase in HO-1 mRNA in RHF. The change in HO was unique to HO-1, because neither the HO-2 transcripts (;1.3 and 1.9 kb) nor the HSP 70 mRNA was altered in either ventricle. This increase in HO-1 mRNA in RV was accompanied by a two-fold increase in immunoreactive HO-1 protein, as judged by Western blot analysis, as well as by a significant increase in cGMP levels. There was, however, no significant increase in RV total nitric oxide synthase activity in RHF. Furthermore, since norepinephrine infusion also increased HO-1 transcript and protein levels, the HO-1 system probably was induced in RHF by the increased interstitial norepinephrine levels known to occur in failing myocardium. This differential regulation and induction of HO-1 gene in the failing ventricle might be one of the defense mechanisms by which the heart attempts to protect from stress caused by congestive heart failure.