Biomedical subjects

N Hikita

Publications and source records attributed to N Hikita.

At least 19 recordsLinked to original sources

PubMed2000

Effects of FTY720, a novel immunosuppressant, on experimental autoimmune uveoretinitis in rats.

The immunosuppressive properties of FTY720, a novel immunosuppressant obtained by structural modification of ISP-I isolated from the fermentation broth of Isaria sinclairii, were studied in experimental autoimmune uveoretinitis (EAU) in rats. Lewis rats were immunized with S-antigen and treated with FTY720 (0. 03, 0.06, 0.1 mg kg(-1)day(-1)) or distilled water for 16 days after the immunization. FTY720 suppressed the incidence and intensity of EAU in a dose-dependent manner as demonstrated by clinical and histological examinations. The drug significantly suppressed the serum levels of antibodies to S-antigen and antigens-specific lymphocyte proliferation. The number of peripheral lymphocytes, but not neutrophils, was markedly reduced by FTY720 treatment. FTY720 also suppressed the intensity of EAU when it was given from the day of EAU onset. These results indicate that FTY720 has intense immunosuppressive effects on EAU in rats and may be a potential candidate for use in the treatment of patients with autoimmune uveitis.

Animals↗

PubMed2000

Soluble Fas ligand and soluble Fas in ocular fluid of patients with uveitis.

AIMS: To investigate the presence of soluble Fas ligand (sFasL) and soluble Fas (sFas) in ocular fluid of patients with uveitis. METHODS: Samples of aqueous humour (AH, n=17), vitreous fluid (n=9), and serum (n=60) were collected from patients with uveitis which included Behçet's disease, Vogt-Koyanagi-Harada disease, sarcoidosis, human T lymphotropic virus type 1 (HTLV-I) uveitis, sympathetic ophthalmia, HLA-B27 associated acute anterior uveitis, and ocular toxoplasmosis. The AH of patients with age related cataract without uveitis obtained during cataract surgery was used as controls (n=20). The amounts of sFasL and sFas were measured by enzyme linked immunosorbent assay. RESULTS: Significant amounts of sFasL were detected in AH of patients with age related cataract (non-uveitis group). sFasL was also detected in AH of patients with uveitis, though the amounts were slightly lower than those in the non-uveitis group. On the other hand, the levels of sFas in AH of patients with uveitis were significantly higher than those in controls. As for the disease activity, the levels of sFasL and sFas in the vitreous fluid of patients with active uveitis were significantly higher than those in inactive uveitis. sFasL in the serum of healthy donors and patients with uveitis was below detectable levels, except for patients with HTLV-I uveitis who had significant amounts of sFasL in the serum. The levels of sFas in the serum of patients with Behçet's disease, sarcoidosis, and HTLV-I uveitis were significantly higher than those of healthy donors. CONCLUSIONS: sFasL is present in the AH of non-uveitic eyes with age related cataract. Intraocular levels of sFasL and sFas are significantly increased in uveitis, particularly in active uveitis. These data suggest that intraocular sFasL and sFas may have a regulatory role in uveitis.

Adult↗

PubMed2000

Kinetics of apoptotic cells in experimental autoimmune uveoretinitis.

PURPOSE: To investigate the role of apoptosis in immunopathogenic mechanisms of experimental autoimmune uveoretinitis (EAU), the kinetics of apoptotic cells and expression of Fas and Fas ligand (FasL) in the eye with EAU were studied. METHODS: Male inbred Lewis rats were immunized with S-antigen (40 microg/rat), and eyes were examined to detect apoptotic cells on days 1, 4, 8, and 10 post-immunization and days 0, 2, 4, 6, and 8 after the onset of EAU. The clinical and pathologic scores were used for estimating EAU. Apoptotic cells were analyzed by TdT-mediated dUTP nick-end labeling, electron microscopic and immunohistologic examinations, and agarose gel electrophoresis. The anti-rat Fas and anti-rat FasL antibodies were used to examine the expression of Fas and FasL. RESULTS: Apoptotic cells were detected in the infiltrating cells in the aqueous humor, the vitreous body, the iris-ciliary body, and the retina. Apoptotic cells were observed as early as the day of EAU onset and reached a peak on day 2 after the disease onset. Fas and FasL were expressed on the infiltrating cells in the aqueous humor and the vitreous. FasL was expressed on resident cells of the ciliary body. The kinetics of the expression of FasL corresponded with the kinetics of apoptotic cells. CONCLUSIONS: Fas-FasL-mediated apoptosis is considered to occur in the eye with EAU and plays a role in the immunopathogenic mechanisms to eliminate ocular infiltrating cells, thereby down-regulating the inflammatory processes.

Animals↗

PubMed1999

Role of hyperinsulinemia in atherosclerotic coronary arterial disease: studies of semi-quantitative coronary angiography.

OBJECTIVE: To evaluate the role of insulin resistance on coronary atherosclerosis, angiographic semiquantitative scores of coronary stenosis and calcification were evaluated. SUBJECTS AND METHODS: Ninety-five non-diabetic subjects with coronary arterial disease were selected from our angiographic data base. Hyperinsulinemia was defined as a serum insulin level of > or = 60.4 IU/l at 120 minutes after 75 g oral glucose challenge. RESULTS: Twenty-three (24%) of the patients exhibited hyperinsulinemia. There was no difference in age or gender between the two subgroups. The incidence of hypertension, smoking habits, hypercholesterolemia, and hyperuricemia were also the same among the insulin resistance subgroups. Subjects with hyperinsulinemia had higher coronary artery scores of stenosis (11.9+/-5.6 vs 8.3+/-5.0, p<0.0001) and calcification (7.5+/-6.3 vs 4.8+/-4.9, p<0.0001). Moreover, the stenosis score had a close linear correlation with the 120 minutes serum insulin level (r=0.266, p=0.009), but not with the fasting level. CONCLUSION: These results suggest that hyperinsulinemia is a risk for coronary arterial disease, and emphasize the severity of coronary atherosclerosis in normal glucose tolerant subjects.

Adult↗

PubMed1999

[A report of two cases suggesting positive influence of pregnancy on uveitis activity].

BACKGROUND: Little is known about the influence of pregnancy on uveitis activity. We report two cases suggesting a favorable influence of pregnancy on the clinical course of uveitis. CASE: A 30-year-old woman who was three months pregnant was suspected Vogt-Koyanagi-Harada disease based on the systemic symptoms and ocular findings of iritis and multi-focal serous retinal detachment. She was positive to human leukocyte antigen (HLA)-DR 4. She was treated only with topical corticosteroids. One month later, the retinal detachment disappeared. Six month later, a healthy baby was born. The fundus of both eyes took on a sunset glow appearance and there has been no recurrence of uveitis. The other case was a 23-year-old woman with Behçet's disease who had several episodes of uveitis in a year even on tacrolimus. Because of pregnancy, all systemic drugs including tacrolimus were discontinued since then. Interestingly, the frequency of uveitis was remarkably decreased during the pregnancy. A normal healthy baby was born. The uveitis has almost completely disappeared since parturition until now. CONCLUSION: It is considered that the increase of intrinsic hormone, especially corticosteroid, and some other factors with pregnancy may give the suppressive influence on uveitis in our cases.

Adult↗

PubMed1998

[Estimated prevalence rate of HTLV-I uveitis in Chikugo].

To estimate the prevalence rate of human T-cell lymphotropic virus type 1 (HTLV-I) uveitis, an epidemiological survey was carried out in the Chikugo District of Fukuoka Prefecture between 1 September and 31 October 1995. The survey was done by sending questionnaires on uveitis patients to all ophthalmological institutes in the district and measuring the serum antibody to HTLV-I. The recovery rate of the survey was 39 of 48 institutes (81.3%). A total of 357 patients with uveitis were reported in the survey, of whom 317 (88.8%) were tested for their seropositivity to HTLV-I. Among them, 18 patients were counted as having HTLV-I uveitis (HU) on 1 October 1995. Based on these data together with the age- and sex-specific population of HTLV-I carriers in the Chikugo District, it was estimated that the crude prevalence rates of HU per 100,000 HTLV-I carrier population were 58.6 in males, 152.0 in females, and 112.2 in both sexes. The prevalence rate of HU was slightly higher than that of HTLV-I associated myelopathy.

Adult↗

PubMed1998

[Treatment of cytomegalovirus retinitis in AIDS with an intraocular sustained-release ganciclovir implant].

Active cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) was treated with an intraocular sustained-release ganciclovir implant. A total number of 19 implants were performed in 15 eyes of 9 AIDS patients. The intraocular sustained-release ganciclovir was effective in preventing reactivation of CMV retinitis in 15 of the 19 implants, ineffective in 3, and undetermined in 1. All ineffective cases had been resistant to ganciclovir therapy before the implants. Vision after the therapy was maintained at better than 0.5 except for one eye. There were no serious ocular complications caused by the therapy. Among 5 patients with unilateral CMV retinitis, 2 unaffected eyes developed CMV retinitis during this therapy. In addition, another patient developed presumed CMV infection in other systemic organs. Based on these data, the intraocular sustained-release ganciclovir implant was considered to be useful for the treatment of CMV retinitis in AIDS.

AIDS-Related Opportunistic Infections↗

PubMed1998

[Involvement of glucose metabolism abnormalities and insulin resistance in atherosclerotic coronary artery disease: semiquantitative coronary angiography study].

Insulin resistance is known to be important in the aggravation of established coronary risk factors, but it is unclear whether insulin resistance might cause coronary artery disease as diabetes mellitus. To evaluate the relationship between insulin resistance and coronary atherosclerosis, the angiographic semiquantitative score of coronary atherosclerosis was investigated in 216 patients (175 males, 41 females) with coronary artery disease and the varying degrees of glucose metabolism including insulin resistance. Insulin resistance was estimated by plasma insulin level at 120 min after the 75g oral glucose tolerance test. Patients were divided into 3 groups according to the levels of glucose metabolism: 37 patients with treated diabetes mellitus, 48 with glucose intolerance and non-treated diabetes, and 131 with normal glucose tolerance. Multivessel disease was more frequently seen in the treated diabetes group (67.6%) than in the glucose intolerance and non-treated diabetes groups (43.8%) and in the normal glucose tolerance group (40.5%). The severity of coronary artery stenosis (8.5 +/- 3.9 vs 7.6 +/- 3.7 vs 6.6 +/- 3.7) and calcification (6.5 +/- 6.3 vs 3.3 +/- 3.3 vs 4.0 +/- 4.8) were significantly higher in the treated diabetes group than in other groups. Distal coronary lesions were significantly more frequent in the treated diabetes group (61.1% vs 17.6% vs 27.4%) than in other groups. Half of the patients in the normal glucose tolerance group had hyperinsulinemia. Multivessel disease was significantly more frequent in the insulin resistant subgroup than in the insulin non-resistant subgroup (59.4% vs 25.0%, p = 0.011). The severity of coronary artery stenosis was significantly higher in the insulin resistant subgroup than in the insulin non-resistant subgroup (8.6 +/- 3.9 vs 5.6 +/- 3.0, p < 0.001), but the severity of coronary artery calcification was not significant. Distal coronary lesions showed a tendency to increase in the insulin resistant subgroup (37.5% vs 12.0%, p = 0.081). These results suggest that insulin resistance is an important risk factor for coronary artery disease in patients with normal glucose tolerance, and is related to the severity and multiplicity of coronary atherosclerosis as in patients with diabetes.

Blood Glucose↗

PubMed1997

Use of topical FK506 in a corneal graft rejection model in Lewis rats.

PURPOSE: To evaluate the immunosuppressive effect of topical FK506 on allograft corneal rejection in rats. METHODS: Lewis rats were used as recipients and Fisher rats as corneal graft donors. In Experiment 1, all rats received intraperitoneally FK506 (0.3 mg/kg per day) for 7 days to ensure equal baseline parameters. The rats then were assigned randomly to treatment with topical 0.3% FK506 or vehicle alone. In another set of experiments, rats were treated only with topical treatment. The grafts were inspected by clinical evaluation. Corneas obtained at the time of maximum rejection were used for histology and immunohistochemistry. RESULTS: The selected combination of rat strains caused 100% graft rejection in untreated animals within 2 weeks after the penetrating keratoplasty. In the treated animals, rejection was delayed until the end of topical therapy. One third of corneal grafts remained clear until day 30. Histologic and immunohistochemical studies confirmed the clinical evaluations. Untreated rat corneas had a large number of infiltrating helper-inducer T cells, macrophages, interleukin-2 receptor-expressing cells, and Ia-antigen-expressing cells. At the same timepoint, topically treated corneas showed a limited inflammatory response characterized by a 2/3 reduction in the number of infiltrating helper and cytotoxic cells, and a five-fold decrease in the expression of class I and class II major histocompatibility antigens. CONCLUSIONS: Topical FK506 treatment is an effective way of preventing corneal graft rejection in the Lewis rat corneal graft model. It shows promise as a drug to prevent corneal graft rejection in humans.

Administration, Topical↗

PubMed1997

[Human T-lymphotropic virus type 1 uveitis in children].

We report here five pediatric patients with human T-lymphotropic virus type 1 (HTLV-I) uveitis. The patients were one boy and four girls aged between 3 and 14 years. The transmission route was considered to be breast feeding from their mothers. All patients had unilateral uveitis and the ocular symptoms were similar to those in HTLV-I uveitis in adults. The ocular inflammation responded to therapy with topical or systemic corticosteroids, but recurred in three patients. HTLV-I provirus DNA was detected by polymerase chain reaction (PCR) from infiltrating cells in the anterior chamber in one patient. The percentage of HTLV-I-infected cells in the peripheral blood mononuclear cells was measured by quantitative PCR, and the values were high (2.9 approximately 7.3%) in three cases tested as compared with an asymptomatic carrier. These five cases show that HTLV-I uveitis can be induced in a relatively short period (3 approximately 10 years) after the viral infection, and that HTLV-I uveitis should be considered as one possible etiology of uveitis in children, particularly in a viral endemic area.

Adolescent↗

PubMed1996

HTLV-I uveitis.

Human T-cell lymphotropic virus type I (HTLV-I) is known to cause adult T-cell leukemia/T-cell lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. Recent seroepidemiologic, clinical, and virologic studies indicate that the virus is also related to a certain type of uveitis, which has been classified as uveitis without defined etiologies or idiopathic uveitis. According to the seroepidemiologic survey, the seroprevalence of HTLV-I in patients with idiopathic uveitis was significantly higher than that of two control groups, that is, patients with uveitis with defined etiologies and patients with nonuveitic ocular diseases. Clinically, the uveitis seen in HTLV-I carriers is characterized by moderate to severe cellular infiltration in the eye and by moderate retinal vasculitis, and the intraocular inflammation responds well to corticosteroid therapy. Interestingly, 25% of female patients with the disease had a previous history of Graves disease with hyperthyroidisms. The following virologic, molecular biologic findings suggest that cytokines produced by HTLV-I-infected T cells in the eye play the central role in the pathogenic mechanisms of the uveitis: (a) the virus load in the peripheral blood monocytes analyzed by the quantitative polymerase chain reaction methods was significantly greater in patients with the uveitis than in asymptomatic carriers, (b) the proviral DNA of HTLV-I and the gene expression of the virus at the mRNA level was detected in the infiltrating cells from the eyes of the patients, (c) the virus particles were detected by electron-microscopic examination in the T-cell clones established from the intraocular fluid of the patients, and (d) the HTLV-I-infected T cells produced a variety of cytokines without any stimuli, such as interleukin (IL)-1 alpha, IL-2, IL-3, IL-6, IL-8, IL-10, tumor necrosis factor alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Based on the seroepidemiologic, clinical, and virologic data, the uveitis seen in HTLV-I carriers is considered to be a distinct clinical entity related to HTLV-I infection, and the disease is designated as HTLV-I uveitis.

Adolescent↗

PubMed1996

Compound 48/80-induced conjunctivitis in the mouse: kinetics, susceptibility, and mechanism.

A mouse model of conjunctivitis has been developed by topical application of compound 48/80 (C48/80), an agent that triggers mast cell degranulation. We examined the responsiveness of C57BL/6, C3H/HeN, and ASW/J mouse strains to C48/80 stimulation, and of a mutant strain with mast cell depletion (WBB6F1/J and its sham control). Conjunctivae were collected and examined histopathologically at 15 min and 1,6,24,48 and 72 h after topical C48/80 administration. Conjunctival inflammation developed in all strains, although the severity varied. The conjunctivitis was characterized clinically by irritation, discharge, erythema, and chemosis. Pathology showed conjunctival infiltration with neutrophils, macrophages, CD4+ T lymphocytes, and a few eosinophils. Degranulation of mast cells and evacuation of goblet cells were also observed. Late-phase inflammatory reactions peaked 6-24 h after C48/80 administration and resolved by 48-72 h. WBB6F1/J mice had much less inflammation than their sham controls. In conclusion, topical C48/80 induced a conjunctival inflammatory response similar to allergen-induced conjunctivitis. The depletion of mast cells significantly reduced the inflammation. This model which consistently mimics the clinical signs and histopathological processes of allergic conjunctivitis in humans, is practical and reliable for the evaluation of new anti-allergic medications and for the investigation of conjunctival cellular responses in the allergic inflammatory cascade.

Animals↗

PubMed1995

Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis.

We studied the effect of monoclonal antibodies (mAbs) against CD54 (intercellular adhesion molecule-1; ICAM-1) and CD11a (lymphocyte function-associated antigen-1; LFA-1) on the prevention and treatment of endotoxin-induced uveitis (EIU). When treated at the time of endotoxin injection the mean number of inflammatory cells infiltrating the eye +/- S.E.M. on histologic sections was 469.2 +/- 51.9 for controls, 13.8 +/- 2.6 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 195.8 +/- 48.8 for rats receiving anti-LFA-1 mAb (P = 0.0003). When treated after the start of inflammatory disease, the mean number of infiltrating inflammatory cells +/- S.E.M. was 273.0 +/- 30.7 for controls, 6.4 +/- 1.7 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 54.2 +/- 7.6 for rats receiving anti-LFA-1 mAb (P < 0.0001). The mean number of cells per milliliter of aqueous humor +/- S.E.M. was 1867.6 +/- 321.8 for controls, 21.7 +/- 5.3 for rats receiving anti-ICAM-1 mAb (P < 0.0001), and 295.1 +/- 71.2 for rats receiving anti-LFA-1 mAb (P < 0.0001). MAbs against ICAM-1 and LFA-1 significantly inhibited the development of EIU and were effective in treating clinically evident ocular inflammatory disease.

Animals↗

PubMed1995

Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat.

FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.

Administration, Topical↗

PubMed1994

Experimental melanin-protein-induced uveitis in the Lewis rat. Immunopathologic processes.

PURPOSE: To study the immunopathology of experimental melanin-protein-induced uveitis in the Lewis rat. METHODS: Rats were immunized with bovine ocular melanin protein. The kinetics of experimental melanin-protein-induced uveitis was studied by clinical examination and immunopathology. Cellular and humoral responses were evaluated by lymphocyte proliferation, delayed-type hypersensitivity, and agglutination. After clinical disease subsided, recurrent experimental uveitis was induced with a low-dose footpad injection of lipopolysaccharide. RESULTS: Experimental melanin-protein-induced uveitis was characterized by bilateral uveal infiltration mainly with lymphocytes and monocytes. Delayed-type hypersensitivity, lymphocyte proliferation, and agglutination to bovine ocular melanin protein were positive. Expressions of major histocompatibility complex class II and intercellular adhesion molecule-1 were observed before ocular infiltration. The predominantly infiltrating cells were CD4+ lymphocytes. Experimental melanin-protein-induced uveitis subsided within 1 month, spontaneously recurred within 1 week in approximately one quarter of the rats, and was inducible in most rats with 5 micrograms of lipopolysaccharide confirmed by histopathology. CONCLUSIONS: Experimental melanin-protein-induced uveitis is a T-cell-mediated autoimmune uveitis, resembling noninfectious recurrent iridocyclitis and choroiditis in humans.

Animals↗

PubMed1994

Ocular inflammation stimulated by the immunomodulator AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate].

The purpose of this study was to investigate the effect of a novel immunomodulator, AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate], in the eye. Lewis rats were injected intravitreally with AS101 at a concentration of 13 micrograms/ml in one eye and BSS in the contralateral eye. Control animals were injected with BSS into the central vitreous of both eyes. Ocular inflammation was evaluated at 20 hours by histology, immunopathology, and by cell count, protein and cytokine measurement in the aqueous humor. At 20 hours, eyes injected with AS101 developed iridocyclitis and mild vitritis versus minimal inflammation and/or protein in contralateral eyes or eyes of control animals (p = 0.0121). The inflammatory infiltrate was mixed in character. Major Histocompatibility Complex (MHC) class II antigens and intercellular adhesion molecules (ICAM-1) were expressed in the anterior segment of eyes injected with AS101. In the aqueous humor of these eyes there were significant quantities of inflammatory cells, protein (mean +/- SEM = 11.2 +/- 2.3 mg/ml) and the cytokine interleukin 6 (IL-6) (450 units/ml) compared with contralateral eyes (p = 0.0005 for inflammatory cells; protein, mean +/- SEM = 1.6 +/- 0.17 mg/ml; IL-6 = 12 units/ml) and both eyes of control animals injected with BSS (p = 0.8955 for inflammatory cells; protein, OD = 1.5 mg/ml, OS = 0.7 mg/ml; IL-6, OD = 8 units/ml, OS = 13 units/ml). AS101 has a local inflammatory effect in the eye. This compound may activate ocular inflammation by releasing cytokines such as IL-6.

Adjuvants, Immunologic↗

PubMed1994

[Quantification of reversible perfusion abnormality using exercise-stress thallium SPECT before and after coronary revascularization].

Reversible myocardial perfusion abnormality was quantified by bull's eye and unfolded surface mapping methods in exercise thallium SPECT before and after coronary revascularization in 47 patients with angina pectoris, including 34 patients with previous myocardial infarction (PMI) and 13 with effort angina (AP). There was no difference in the incidence or extent of myocardial ischemia between the 2 groups before revascularization. However, the ischemic scores were significantly smaller in PMI group preoperatively than the reductions of the ischemic scores after revascularization. The ischemic scores, preoperatively estimated reversible perfusion abnormality was 32%, 69% and 48% of the improvement of the ischemic score (extent score, severity score, and ischemic area, respectively). Using the 3 ischemic scores, the improvement of perfusion abnormality was well predicted in 70-89% of AP patients but 35-57% of PMI patients. Thus, quantitative analysis in stress thallium SPECT is useful for detecting myocardial ischemia and evaluating the effect of coronary revascularization. However, about a half of myocardial viability was underestimated in one third of PMI patients by the conventional exercise-stress thallium SPECT study.

Adult↗

PubMed1993

Plasma noradrenaline as an indicator of functional state in hearts with mitral stenosis: the influence of acutely reduced left atrial pressure by balloon mitral commissurotomy.

To investigate the mechanism in which plasma noradrenaline concentration (pNA) is elevated in heart failure, the effect of balloon mitral valvuloplasty was used as a model of acute manipulation of the left atrial pressure reduction in ten patients with mitral stenosis. Gorlin mitral valve area and pNA were correlated with New York Heart Association functional class and found to have a significant exponential inverse relationship with each other ([pNA, pg/ml] = 198.9 x [mitral valve area, cm2]-0.696; P = 0.003). Elevated pNA could be partially explained by a reduced cardiac index (CI) ([pNA, pg/ml] = 403.4 x [CI, l/min/m2]-0.889; P = 0.027; r = 0.495), especially in severely failed hearts, but not by pulmonary capillary wedge pressure (PCWP). However, the percent changes (% delta) of variables early after balloon valvuloplasty exhibited a paradoxical contrast; % delta pNA showing a clear negative exponential correlation with % delta PCWP ([% delta pNA] = 436.0 x [% delta PCWP + 80]-0.679 - 80; P = 0.021), but not with % delta CI. These results suggest that pNA should be considered an indicator of cardiac functional class in mitral stenosis. PNA is modulated by both cardiac index and pulmonary capillary pressure, but in different ways.

Adult↗