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Biomedical subjects

C M Frampton

Publications and source records attributed to C M Frampton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adult coeliac disease: prevalence and clinical significance.

BACKGROUND AND AIMS: Although coeliac disease is a common condition, the role of population screening is not clear. The aim of this study was to determine the prevalence and clinical significance of coeliac disease in the adult population of Christchurch, New Zealand. METHODS: A total of 1064 adults randomly selected from the 1996 Christchurch electoral rolls were enlisted. The subjects were screened for coeliac disease using the anti-endomysial antibody test (EMA), and all those with positive tests were reviewed and underwent a small bowel biopsy. RESULTS: Twelve of the 1064 persons tested (1.1%) were EMA positive and all had small bowel biopsy histology consistent with coeliac disease. Two of the 12 subjects were previously known to be EMA positive although neither had a small bowel biopsy. One additional subject with known and treated coeliac disease was also enrolled but was EMA negative. Thus, the overall prevalence of coeliac disease was 13 of 1064 subjects (1.2%, or 1:82), 10 of whom were newly diagnosed (0.9%, or 1:106) and three were previously known or suspected to have coeliac disease (0.3%, or 1:355). The prevalence in both sexes was similar. Nine of the 12 EMA-positive coeliac disease subjects identified by the use of screening reported symptoms, of which tiredness and lethargy were the most common. The subjects were of normal stature, although females tended to be lean. None of the subjects were anaemic, but four were iron deficient and four folate deficient. Five of the 12 had sustained bone fractures. Bone mineral density was reduced in males but not in females. CONCLUSIONS: The prevalence of coeliac disease in the adult population of Christchurch, New Zealand, is 1.2%. Unrecognized coeliac disease which was detected by population screening was three-fold more common than proven or suspected coeliac disease. Population screening may identify subjects who could benefit from treatment.

Adult↗
PubMed2000

Beneficial renal and hemodynamic effects of omapatrilat in mild and severe heart failure.

Omapatrilat is a member of the new drug class of vasopeptidase inhibitors that may offer benefit in the treatment of heart failure (HF) through simultaneous inhibition of angiotensin-converting enzyme and neutral endopeptidase. We examined the effects of omapatrilat in a placebo-controlled crossover study using a pacing model of HF. Seven sheep were paced sequentially at 180 bpm (mild HF) and then 225 bpm (severe HF) for 7 days each. Omapatrilat (0.005 mg/kg) or vehicle was administered by intravenous bolus on days 4 to 7 of each paced period. Omapatrilat lowered mean arterial and left atrial pressure and increased cardiac output acutely and chronically in both mild and severe HF (P<0.01 for all). Plasma atrial and brain natriuretic peptide and cGMP levels were stable acutely (P=NS), while brain natriuretic peptide increased after repeated dosing in severe HF (P<0.05). Plasma renin activity rose, whereas angiotensin II and aldosterone levels fell after acute and repeated dosing in both states (P<0.01 for all). Omapatrilat increased urinary sodium excretion by day 7 in both mild and severe HF (P<0.05). Effective renal plasma flow and glomerular filtration rate increased or were stable after omapatrilat in mild and severe HF after both acute and repeated dosing. Omapatrilat exhibited pronounced acute and sustained beneficial hemodynamic and renal effects in both mild and severe heart failure.

Aldosterone↗
PubMed2000

Effects of terbutaline and budesonide on sputum cells and bronchial hyperresponsiveness in asthma.

Previous studies have shown that the regular administration of short acting beta-agonists can be associated with adverse effects on airway caliber and bronchial hyperresponsiveness (BHR) and that this may occur through a proinflammatory mechanism. The aim was to explore possible adverse effects of high-dose beta-agonist therapy and to assess any adverse interaction with corticosteroids. We undertook a randomized, crossover study to investigate the effects of 6 wk of treatment with regular terbutaline (1 mg four times a day), regular budesonide (400 microg twice a day), combined treatment, and placebo in subjects with mild to moderate asthma. Major endpoints were PD(15) saline, PD(20) methacholine, and induced sputum differential cell counts. Thirty-four subjects were randomized and 28 completed the study. PD(15) saline decreased on terbutaline alone compared with placebo treatment and on combined treatment compared with budesonide alone (mean fold decrease of 0.57 [95% CI = 0.36, 0.90] and 0.65 [95% CI = 0.43, 0.97], respectively). PD(20) methacholine was not affected by the use of terbutaline either alone or in combination with budesonide. The percentage of eosinophils in induced sputum increased during terbutaline treatment alone compared with placebo (median 8.3% versus 4.4%, p = 0.049). The addition of terbutaline to budesonide did not affect the percentage of eosinophils compared with budesonide treatment alone. These findings support the hypothesis that short-acting beta-agonists have a permissive effect on airway inflammation and that when used in high dose there may be an unfavorable interaction with inhaled corticosteroids.

Administration, Topical↗
PubMed1999

Seroprevalence of Helicobacter pylori in the adult population of Christchurch: risk factors and relationship to dyspeptic symptoms and iron studies.

AIM: To determine the prevalence of Helicobacter pylori infection in subjects randomly selected from the Christchurch population and to determine the risk factors and symptoms related to the infection. METHODS: A list of names was randomly generated from the 1996 electoral roll and subjects were sequentially contacted and invited to participate. A questionnaire on dyspeptic symptoms was completed and the subject's serum was analysed for H. pylori antibodies using the Roche method. Equivocal samples were retested by the Meridian method. RESULTS: One thousand and sixty-four subjects participated in the study. In four subjects results for H. pylori were indeterminate and these subjects were excluded from analysis. Of the remaining 1060 subjects, 254 (24.0%) were seropositive for H. pylori. The seropositivity in males (n=444) was 25.9% and in females (n=616) 22.6%. On multivariate analysis age, ethnicity, low income and smoking > 20 cigarettes per day were all independent predictors of H. pylori seropositivity. H. pylori positive subjects had shorter stature compared to those who were seronegative. The symptom scores for dyspepsia were similar in both the seropositive and seronegative subjects. In males the serum iron levels were lower in seropositive subjects but there were no significant differences in serum ferritin in either males or females between seropositive and seronegative subjects. CONCLUSION: H. pylori is a common infection in the Christchurch community with the prevalence increasing significantly with age. H. pylori positive subjects had shorter stature and in males lower serum iron levels were observed. Infection was not associated with an increased risk of dyspeptic symptoms.

Adult↗
PubMed1999

The prevalence of malnutrition in elderly hip fracture patients.

AIM: To determine the prevalence of protein and energy malnutrition in elderly patients with a fracture of the proximal femur, in New Zealand. METHODS: Consecutive elderly patients (65 years and over) admitted to Christchurch Hospital with a fracture of the proximal femur over a four-month period were recruited. Nutritional indices were measured within three days of admission. These included triceps skinfold thicknesses, mid upper arm circumference, serum albumin and pre-albumin. RESULTS: Forty-two per cent of patients had at least two, and nine per cent had three, indicators of protein and energy malnutrition present on admission. There was no significant difference in the prevalence of malnutrition between young old (<80 years) and old old (80 years and over) patients. Patients residing in an institution had lower mean protein reserves, as indicated by lower corrected arm muscle area (p=0.003) and pre-albumin levels (p=0.09), than those living in the community. A drink, rather than a pudding or biscuit, was the preferred protein and energy supplement form. Ensure Plus (lactose-free) and Fortisip (lactose-free) were the most preferred drink supplements. CONCLUSION: Protein and energy malnutrition is common in elderly New Zealanders who fracture their femur. The prevalence is comparable to overseas data. These patients prefer nutritional supplementation given as a drink.

Aged↗
PubMed1999

Late results of surveillance of clinical stage I nonseminoma germ cell testicular tumours: 17 years' experience in a national study in New Zealand.

OBJECTIVE: To re-evaluate a national prospective study in New Zealand after 17 years to define whether orchidectomy alone and surveillance for nonseminoma germ cell testicular tumour (NSGCTT) is a sound policy and matches the results achieved by other treatment protocols. PATIENTS AND METHODS: Between 1980 and 1997, 248 men with stage I NSGCTT, from six New Zealand centres, were managed by orchidectomy alone and surveillance, with treatment of relapses using combination chemotherapy. RESULTS: Seventy of the 248 patients (28%) relapsed; 42 of 92 (46%) with vascular and/or lymphatic invasion (VLI) in the primary tumour relapsed, whereas only 26 of 151 (17%) without this feature relapsed (P<0.001). VLI was the only identifiable risk factor for relapse in this series. Only one relapse occurred >28 months after orchidectomy. Despite poor compliance in some patients (12%) their survival was not prejudiced. Three patients died from disease despite chemotherapy at relapse. At 17 years and a median follow-up of 53 months, 242 of the 248 men are disease-free and the disease-specific survival rate is 98%. CONCLUSIONS: This study shows that orchidectomy alone and treatment of relapses produces excellent long-term results without the adverse effects associated with retroperitoneal node dissection or elective chemotherapy for high-risk cases.

Adolescent↗
PubMed1999

Increased vibrissa growth in transgenic mice expressing insulin-like growth factor 1.

Insulin-like growth factor 1 (IGF-1) mediates many of the actions of growth hormone. Overexpression of IGF-1 has been reported to have endocrine and paracrine/autocrine effects on somatic growth in transgenic mice. To study the paracrine/autocrine effects of IGF-1 in hair follicles, transgenic mice were produced by pronuclear microinjection of a construct containing a mouse ultra-high sulfur keratin (UHS-KER) promoter linked to an ovine IGF-1 cDNA. This UHS-KER promoter has previously been shown to direct expression of a reporter gene to the hair follicles of transgenic mice. Four transgenic mouse lines were established as a result of microinjection of 435 embryos. Transgene expression was found in skin at day 8 and day 15 of age in three of the lines. Progeny tests were carried out by mating two of the transgenic expressing males to nontransgenic females. Mice from one line were all nonexpressors while four of the 12 mice from the other showed integration of the transgene and three expressed transgene IGF-1 mRNA in the skin. Vibrissa growth at 11-21 d of age was significantly greater in transgenic expressors than in their nontransgenic littermates. Specifically, the increase in vibrissa length for transgenics at days 11-16 (20.5%) is approximately 2-fold compared with days 16-21 (11.9%). These results demonstrate that local overexpression of IGF-1 in transgenic mice is capable of stimulating vibrissa growth during the first neonatal hair cycle.

Animals↗
PubMed1999

Cerebrovascular disease as a general medicine discharge diagnosis: assessment of diagnostic agreement on case note review.

BACKGROUND: Accurate clerical coding of discharge diagnoses is important partly because results may be used to derive a recommended costing for hospital length of stays (LOS). Some authors think that discharge coding undertaken by clinicians will result in less diagnostic misclassification than clerical coding. This presupposes a high degree of between-observer diagnostic agreement between clinicians. AIMS: To compare discharge coding undertaken by two general physicians, for patients receiving a clerical discharge code of cerebrovascular disease. The recommended LOS was then calculated from each observer's discharge codes using the Physicians Diagnosis Related Group Working Guidebook. RESULTS: Eighty-two cases were coded as stroke by the clerical coder. Both medical coders agreed with this diagnosis in 68 (83%) of these cases. The corresponding figure for cases coded by the clerical coder as transient cerebral ischaemia was 47% (32/68) agreement between all three observers. Correcting for chance agreement between medical observers using the kappa statistic, a value of 0.64 was obtained for the combined stroke and transient cerebral ischaemia discharges, suggesting moderate diagnostic agreement. Using the clerical coder's results, the mean recommended LOS for all cases of cerebrovascular disease over the study period was calculated at 6.68 days. The corresponding values for the two medical coders were 6.68 days and 6.75 days. CONCLUSIONS: Diagnostic agreement between clinicians was moderate. Consideration of alternative diagnostic possibilities and the difficulty in determining the duration of neurological deficit were the main reasons for diagnostic disagreement. The mean recommended LOS was similar, however, when comparing results from all three observers.

Adult↗
PubMed1999

Blood pressure and vasoactive hormones in mild preeclampsia and normal pregnancy.

OBJECTIVE: Changes in vasoactive hormones are reported to play an important role in the pathogenesis of preeclampsia linking placental hypoperfusion with hypertension, systemic disease, and proteinuria. We, therefore, studied diurnal patterns of vasoactive hormones in mild preeclampsia. METHODS: Venous blood samples were drawn every 2 h over 25 h for measurements of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, renin activity, and aldosterone and two urine collections (12 h each) for stable prostaglandin metabolite measurements. The patients were nine women with mild preeclampsia and, for comparison, nine control women matched for gestation and parity. RESULTS: Women with mild preeclampsia had higher norepinephrine levels throughout 25 h, and lower systemic prostacyclin production as measured by the urinary 2,3-dinor-6-keto PGF1 alpha excretion during the daytime. Plasma endothelin and ANP and BNP concentrations tended to be higher throughout 25 h in preeclampsia, but differences between the two groups did not reach levels of statistical significance. Plasma renin activity and aldosterone did not differ between the groups. Whereas control women exhibited a diurnal variation in plasma norepinephrine, ANP, BNP, and aldosterone, and in both urinary prostacyclin and thromboxane A2 metabolites, this was less distinct or absent in patients with mild preeclampsia. CONCLUSIONS: We conclude that mild preeclampsia is associated with elevated plasma norepinephrine levels, lower systemic daytime production of prostacyclin, and blunting of the normal diurnal variation for a number of indices including plasma levels of BNP, ANP, norepinephrine, and aldosterone, and urinary prostacyclin metabolites.

Adult↗
PubMed1998

Gallbladder volume: comparison of diabetics and controls.

Diabetics are known to have an increased prevalence of gallstones. The aim of this study was to investigate whether diabetics have increased gallbladder volumes that would predispose to stasis, nucleation of cholesterol crystals, and gallstone formation. The gallbladder volume of 271 diabetic subjects and 277 controls was determined by ultrasound using the ellipse formula. Gallbladder volume was also determined by the sum of the cylinders method in 143 cases with a strong correlation (r = 0.89) between the two methods. Using analysis of variance, gallbladder volume was influenced by both diabetic type (NIDDM = 33.68 cm3, IDDM = 26.84 cm3, controls = 29.05 cm3; P = 0.018) and the presence of gallstones (gallstones = 32.04 cm3, no gallstones = 27.58 cm3; P = 0.018). The variation in gallbladder volume between NIDDM, IDDM, and control subjects was influenced by the presence of gallstones (P = 0.024, interaction term from ANOVA). Significant differences (P < 0.001) were only found between NIDDM vs IDDM and NIDDM vs control in the nongallstone group (NIDDM = 34.33 cm3, IDDM = 25.08 cm3, control = 25.17 cm3). Males had significantly larger gallbladder volumes than females: 31.98 cm3 vs 27.74 cm3 (P = 0.023). After the inclusion of BMI, HDL cholesterol, triglyceride, and age in a statistical model with gender and diabetic type in those without gallstones, significant differences were still found between NIDDM and IDDM (P = 0.013) and NIDDM and controls (P = 0.005), demonstrating that NIDDM is an independent predictor for increased gallbladder volume.

Adult↗
PubMed1998

The significance of haemochromatosis gene mutations in the general population: implications for screening.

BACKGROUND: Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown. AIMS: To determine the frequency of HFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis. METHODS: Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis. RESULTS: Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone. CONCLUSIONS: HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis.

Female↗
PubMed1998

Autonomic control of vasovagal syncope.

In the pathophysiological study of vasovagal syncope, the nature of the interaction between baroreceptor sensitivity (BS), sympathetic withdrawal, and parasympathetic activity has yet to be ascertained. Altered BS may predispose toward abnormal sympathetic and parasympathetic responses to orthostasis, causing hypotension that may progress to syncope if there is sympathetic withdrawal. To examine this hypothesis, we monitored blood pressure (BP), heart rate (HR), BS, forearm blood flow, and muscle nerve sympathetic activity (MNSA) continuously in 18 vasovagal patients during 60 degrees head-up tilt, syncope, and recovery. Results were compared with those of 17 patients who were able to tolerate tilt for 45 min. During early tilt, BP was maintained in both groups by an increase in HR and MNSA from baseline (P < 0.01), but BS decreased more in the syncopal group (P < 0.05). At the start of presyncope (mean 2.7 +/- 0.2 min before syncope and 15.2 +/- 12 min after tilt), when BP fell, HR and sympathetic activity remained increased from baseline (P < 0.01). Thereafter, BP and HR correlated directly with sympathetic activity and regressed in linear fashion until syncope (P < 0.001), whereas BS increased to baseline. At syncope, BP, HR, and sympathetic activity fell below baseline (P < 0.01, P < 0.05, and P < 0.01, respectively), but BS did not increase. During recovery, sympathetic activity increased to baseline and BS increased (P < 0.05), whereas HR and BP remained low (P < 0.01 and P < 0.05, respectively). The mechanism for the initiation of hypotension during presyncope remains unknown, but BS may contribute. Vasodilatation and bradycardia during presyncope appear to be more closely related to withdrawal of sympathetic activity than to increased parasympathetic cardiac activity.

Adult↗
PubMed1997

Comparative bioactivity of atrial and brain natriuretic peptides in an ovine model of heart failure.

1. Whereas many studies have detailed the effects of exogenous atrial natriuretic peptide (ANP) infusions in heart failure, and a limited number have examined the effects of brain natriuretic peptide (BNP), none have directly compared the bioactivity of similar doses of ANP and BNP under standard conditions of impaired cardiac function. We compared the hormonal, haemodynamic and renal effects of 3 h infusions of ANP, BNP and a vehicle control in eight sheep with pacing-induced heart failure (225 beats/min for 8-12 days). 2. Infusion of ANP and BNP increased plasma ANP (P < 0.001) (276 +/- 27 versus control 142 +/- 26 pmol/l) and BNP (P < 0.001) (257 +/- 34 versus control 45 +/- 5 pmol/l) respectively, in association with increased cyclic 3',5'-guanosine monophosphate [control, 40 +/- 6; ANP, 53 +/- 6 (P < 0.05); BNP, 57 +/- 7 nmol/l (P < 0.001)]. Metabolic clearance rate and half-life were similar for both peptides. Infusion of ANP and BNP similarly reduced mean arterial pressure [control, 73.0 +/- 1.6; ANP, 67.6 +/- 1.2 (P < 0.01); BNP, 65.7 +/- 1.7 mmHg (P < 0.001)], left atrial pressure (both P < 0.05) (control, 22.0 +/- 0.7; ANP, 19.9 +/- 1.0; BNP, 19.8 +/- 0.9 mmHg) and peripheral resistance [control, 50.3 +/- 4.1 mmHg l-1 min-1; ANP, 46.0 +/- 2.8 (P < 0.05); BNP, 43.8 +/- 4.5 (P < 0.01)], and increased urine volume (2-3-fold, both P < 0.05), sodium excretion (> 10-fold, both P < 0.01) and haematocrit levels relative to control (both P < 0.05). Infused BNP tended to raise plasma ANP levels (by 28 pmol/l), while ANP increased plasma BNP (by 18 pmol/l). Plasma aldosterone was reduced by approximately 40% by both peptides (both P < 0.05). 3. In conclusion, ANP and BNP are both powerfully, natriuretic, similarly suppress aldosterone and appear equipotent in reducing preload and afterload in this model of pacing-induced heart failure.

Aldosterone↗
PubMed1997

Low-dose brain natriuretic peptide infusion in normal men and the influence of endopeptidase inhibition.

1. To assess the threshold dose for bioactivity of brain natriuretic peptide and the role of endopeptidase 24.11 in metabolism of brain natriuretic peptide at physiological plasma levels, we studied eight normal men receiving 2 h infusions of low-dose brain natriuretic peptide [0.25 and 0.5 pmol min-1 kg-1 with and without pretreatment with an endopeptidase inhibitor (SCH 32615, 250 mg intravenously)] in placebo-controlled studies. 2. Plasma brain natriuretic peptide increased 2-fold during the infusion of 0.25 pmol min-1 kg-1 (mean increment above control 3.9 pmol/l, P < 0.001), and tripled (P < 0.001) with 0.5 pmol min-1 kg-1. Plasma renin activity was inhibited by both doses (14.8%, P < 0.01, and 20%, P < 0.001, respectively). A significant natriuresis (56% increase in urine sodium/creatinine ratio, P < 0.02) occurred with the higher dose. Blood pressure, haematocrit, plasma cGMP, atrial natriuretic peptide and aldosterone were unaffected by either dose. 3. Compared with brain natriuretic peptide (0.5 pmol min-1 kg-1) alone, SCH 32615 pretreatment increased peak plasma brain natriuretic peptide (13.4 +/- 0.78 versus 12.4 +/- 0.86 pmol/l, P < 0.05), ANP (7.5 +/- 0.96 versus 5.9 +/- 0.4 pmol/l, P < 0.01) and cGMP (4.8 +/- 1.7 versus 3.9 +/- 1.4 nmol/l, P < 0.001). Plasma renin activity was further suppressed with SCH 32615 pretreatment (29% compared with 20%, P < 0.001). 4. Small acute increments in plasma brain natriuretic peptide (4 pmol/l) have significant biological effects in normal men without altering plasma atrial natriuretic peptide or cGMP.

Adult↗
PubMed1996

Prevalence of gallbladder disease in diabetes mellitus.

A study was undertaken to compare the prevalence of gallstone disease (gallstones observed on ultrasound or history of cholecystectomy) in 308 diabetics and 318 controls. There was a higher prevalence of gallstone disease (GSD) in diabetics (32.7%) compared to controls (20.8%; P < 0.001 chi-squared test). However, when gender was taken into account, the difference was only significant in females (diabetics 41.8% versus controls 23.1%; P < 0.001). Analysis by type of diabetes revealed that subjects with non-insulin-dependent diabetes mellitus (NIDDM) had a higher prevalence of GSD than controls for both genders: males-controls 18.1%, NIDDM 33.3% (P < 0.05), IDDM 15.6% ns; females-controls 23.1%, NIDDM 48.6% (P < 0.001), IDDM 36.3% (P < 0.05). On univariate analysis the following risk factors were associated with gallstones (P < 0.1): increased age, body mass index (BMI), triglycerides, LDL cholesterol, decreased HDL cholesterol, alcohol intake, family history of GSD, and female parity > 3. Using stepwise multiple, logistic regression, the following variables were identified as independently predictive of gallstones for each gender/diabetic combination: Males-NIDDM (N = 54), increased age, and decreased HDL; IDDM (N = 90), age and family history; Females-NIDDM (N = 74), increased age, diabetes, increased BMI, and decreased alcohol; IDDM (N = 91), increased BMI, age, decreased alcohol and family history. The proportion of subjects who underwent cholecystectomy was higher in females (46.7%) compared to males (21.7%; P < 0.01) but there were no differences between diabetics and controls in either sex. In conclusion, there was a higher prevalence of GSD in diabetics compared to controls. However, GSD is multifactorial and only in NIDDM females was diabetes an independent risk factor. The proportion of diabetics and controls with GSD who underwent cholecystectomy was equivalent.

Adolescent↗
PubMed1996

Nitric oxide inhibition in an ovine model of heart failure.

1. The role of nitric oxide (NO) in congestive heart failure was investigated by studying the acute haemodynamic, hormonal and renal effects of N(G)-monomethyl-L-arginine (L-NMMA(, a nitric oxide inhibitor, given as incremental bolus doses in six sheep before (normal) and after induction of heart failure (HF) by rapid left ventricular pacing (LVoff+). 2. 6-NMMA caused significant initial dose-dependent rises in left ventricular systolic pressure, mean arterial pressure (MAP), peripheral resistance (PR) and left atrial pressure and declines in cardiac output in both normal and HF states (maximum response in 2-6 min). These responses were all but abolished when L-arginine was given concurrently with L-NMMA. The dose-response curve for the L-NMMA-induced rise in MAP was shifted to the right following LVP (P < 0.05), which is consistent with previous observations of blunted NO synthase activity in HF. A subsequent decline in MAP and PR to below prebolus levels was observed 30-60 min after L-NMMA administration in the paced state. No significant hormonal or renal effects were observed. 3. In conclusion, the present study confirms the important haemodynamic role played by endogenous NO in the normal state and demonstrates a blunted pressor response to NO inhibition in this model of heart failure.

Animals↗