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Biomedical subjects

A H Morice

Publications and source records attributed to A H Morice.

At least 109 records · Page 6Linked to original sources
PubMed1994

Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary artery pressure is elevated in patients with advanced chronic obstructive pulmonary disease (COPD). Release of atrial natriuretic peptide (ANP) is increased in pulmonary hypertension and this hormone may both selectively vasodilate pulmonary vessels and inhibit pulmonary vascular remodelling. The hypothesis that ANP has a physiological role in protection of the pulmonary circulation from pressure overload, and that it may be beneficial in patients with COPD, has been examined. METHODS: Ten patients with hypoxic COPD were infused for 30 minute periods with saline followed by ANP at 0.4, 2, and 10 pmol/kg/min respectively via a pulmonary artery catheter whilst monitoring haemodynamics and oxygenation. RESULTS: Levels of immunoreactive ANP (irANP) increased from a mean (SD) of 23 (15) pmol/l to a maximum of 94 (41) pmol/l. Neither systemic blood pressure, cardiac output nor total systemic vascular resistance showed any correlation with irANP levels. There were negative correlations between levels of ANP and mean pulmonary artery pressure which fell from 28.7 to 25.9 mm Hg, pulmonary artery wedge pressure which fell from 6.5 to 4.6 mmHg, and total pulmonary vascular resistance which fell from 489 to 428 dynes s cm-5. There was a small fall in PaCO2 from 6.2 to 5.9 kPa, whilst venous admixture and oxygen delivery both increased non-significantly. CONCLUSIONS: At these pathophysiological concentrations there was evidence that ANP selectively reduced right ventricular afterload. These data support the hypotheses that increased plasma levels of ANP may be beneficial in hypoxic COPD, and that endogenous ANP may ameliorate pulmonary hypertension in humans.

Aged↗
PubMed1994

Effect of levcromakalim on hypoxia-, KCl- and prostaglandin F2 alpha-induced contractions in isolated rat pulmonary artery.

The effect of levcromakalim on vascular reactivity was examined in rat isolated pulmonary arterial (PA) rings. Vasoconstriction in response to KCl, prostaglandin F2 alpha (PGF2 alpha) and hypoxia and vasodilatation in response to levcromakalim were studied isometrically in a small-vessel myograph. Levcromakalim caused a dose-dependent inhibition of hypoxic pulmonary vasoconstriction (HPV) in pulmonary resistance vessels (PRV). At 10 microM, levcromakalim caused 58% inhibition in PRV compared with control. In contrast, HPV in large PAs was not significantly inhibited by levcromakalim. At a higher concentration, levcromakalim (100 microM) caused 88% inhibition in PRV and 80% inhibition in PA. The first phase of HPV is not endothelium-dependent, but second-phase contraction is partially endothelium dependent. Levcromakalim (1-10 microM) inhibited contractions induced by low KCl concentrations (10-30 mM) and had no effect on those elicited by 50 to 100 mM KCl in PRV. However, a higher concentration of levcromakalim (100 microM) significantly decreased KCl efficacy in PRV. In PA, all of the concentrations of levcromakalim (1-100 microM) significantly decreased KCl efficacy. The vasorelaxant effects of levcromakalim (1-100 microM) on PRV and PA rings contracted with a low KCl concentration (30 mM) were prevented by tetrabutylammonium (10 microns). PGF2 alpha (1-100 microM)-induced contractions were diminished in both vessel types by levcromakalim (0.1-10 microM). The maximal response to PGF2 alpha was decreased by 77.72% in PRV and 68.50% in PA, respectively, in the presence of 10 microM levcromakalim. Levcromakalim (1 microM) has no additional effect on the transient contraction induced by PGF2 alpha in Ca(++)-free solution in PRV and PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man.

The cough response following inhalation challenge with the sensory nerve irritant resiniferatoxin was compared with that of capsaicin and citric acid in guinea-pig and man. Capsaicin and citric acid gave comparable dose-response curves in the two species. The mean (+/- SEM) concentration producing five coughs in man was 141.3 (1.3) mM (n = 10) for citric acid and 2.8 (1.3) microM (n = 10) for capsaicin. Those for the guinea-pig were 74.1 (1.2) mM (n = 10) for citric acid and 6.0 (2.4) microM (n = 10) for capsaicin. Resiniferatoxin was active at a lower concentration than either citric acid or capsaicin and maximal tolerable cough response was achieved at concentrations of 3 microM (n = 5) in guinea-pig and 300 nM (n = 1) in man. The cough response to resiniferatoxin was greatly prolonged in both guinea-pig and man. Resiniferatoxin, like capsaicin, caused respiratory distress in the guinea-pig which is linked to bronchoconstriction. Resiniferatoxin probably causes cough by stimulation of capsaicin sensitive neurones.

Administration, Inhalation↗
PubMed1993

Amlodipine in patients with angina uncontrolled by atenolol. A double blind placebo controlled cross over trial.

Dihydropyridine calcium antagonists are established second line treatment for angina uncontrolled by beta-adrenergic blockers. Amlodipine is a recently introduced, dihydropyridine with a long half life. In a double blind, placebo controlled, cross over trial we assessed the efficacy and safety of amlodipine in 20 patients with persistent angina despite treatment with atenolol. 17 male patients (mean age 58 y) completed the study. Two patients were withdrawn during placebo because of worsening angina and one withdrew whilst on amlodipine because of palpitations. Compared with baseline, amlodipine prolonged exercise time to S-T segment depression by a median of 12.5%; significantly more than was found with placebo (median 0%). The improvement in exercise time and time to angina also tended to be greater for amlodipine than placebo. GTN consumption, at a median of 1.3/week, was significantly less with amlodipine than placebo (2.8). Attacks of angina were also reduced. Standing systolic and diastolic blood pressures and sitting systolic blood pressure were lower with amlodipine than placebo. Heart rate did not change. There was no change in cardiac output (measured by doppler aortovelography) when amlodipine was added to atenolol. Holter monitor measurements of 24 h maximum and minimum heart rate, heart rate variation and extrasystole counts were the same for amlodipine and placebo. In conclusion, amlodipine is effective in patients with angina inadequately controlled by atenolol alone, and does not interfere with cardiac rhythm or function.

Aged↗
PubMed1993

Vasodilatory action of the calcium antagonist amlodipine on large and resistance pulmonary arteries from normoxic and chronically hypoxic rats.

1. Isolated rat aorta and pulmonary arteries were maximally precontracted with 100 mmol/l KCl, and the vasorelaxation due to the dihydropyridine calcium antagonist amlodipine was measured. The response of large pulmonary arteries (mean lumen diameter 983 microns) was directly compared with that of isolated pulmonary resistance vessels (mean lumen diameter 259 microns) from both normoxic animals and animals exposed to chronic hypoxia. 2. Amlodipine caused a significant relaxation of aorta (P < 0.001). A significant relaxation of large and resistance pulmonary arteries from both normoxic and chronically hypoxic animals was also demonstrated at all doses tested (P < 0.05) or less). 3. Amlodipine produced significantly more relaxation in pulmonary resistance vessels than in large pulmonary arteries from both normoxic and chronically hypoxic rats (P < 0.02). 4. The action of amlodipine was slow in onset and persistent in all vessels studied. In the pulmonary vessels from normoxic animals both the rate of onset and the magnitude of effect was proportional to the drug concentration (P < 0.001). 5. These results demonstrate that amlodipine is a potent inhibitor of KCl-induced contractions in rat pulmonary arteries with a preferential action in pulmonary resistance vessels.

Amlodipine↗
PubMed1993

Effects of atrial natriuretic peptide and nitroprusside on isolated pulmonary resistance and conduit arteries from rats with pulmonary hypertension.

1. The relaxant effects of atrial natriuretic peptide (ANP) and nitroprusside were studied on prostaglandin F2 alpha (PGF2 alpha)-contracted preparations of pulmonary resistance vessels (internal diameter 200-500 microns) and main pulmonary arteries taken from rats with pulmonary hypertension induced by monocrotaline (105 mg kg-1, s.c., 4 weeks previously). Control rats received saline. 2. In preparations from monocrotaline-treated rats, the potencies (negative log EC50) of ANP on resistance vessels (8.45) and main pulmonary arteries (8.25) were similar to those obtained in vessels from control rats (8.78 and 8.53 respectively), whereas those of nitroprusside were significantly less than in controls in both resistance vessels (7.13 compared with 7.63 in controls; three fold decrease in potency) and main pulmonary arteries (6.92 compared with 8.17 in controls; 18 fold decrease in potency). 3. On pulmonary resistance vessels from monocrotaline-treated rats, the maximum relaxant responses to ANP and nitroprusside, and also to pinacidil, were increased compared with controls, and reversal of the PGF2 alpha-induced contraction by these drugs was greater than 100%. In contrast, on main pulmonary arteries from monocrotaline-treated rats, the maximum relaxations to ANP and nitroprusside were not increased relative to controls, and reversal of PGF2 alpha was not greater than 100%. 4. Since the high potency of ANP on pulmonary resistance and conduit arteries is retained in vessels from rats with pulmonary hypertension, whether induced by monocrotaline (this study) or by chronic hypoxia (previous findings), it is postulated that elevation of plasma levels of ANP by use of drugs that inhibit the breakdown of this endogenous peptide, may be one approach to the pharmacological treatment of pulmonary hypertension.

Animals↗
PubMed1993

Steroid prescribing for asthmatics: relationship with Asthma Symptom Checklist and Living with Asthma Questionnaire.

Psychosocial consequences of asthma were assessed for 42 patients attending an out-patient clinic using the Asthma Symptom Checklist (ASC), a five-dimensional scale of experience during asthma attacks, and the Living with Asthma Questionnaire (LWAQ), a unidimensional scale of experience between attacks. Although all subscales of the ASC and the LWAQ correlated with the physician's prescription of steroids, multiple regression showed that 32 per cent of the prescription decision variance was accounted for by two dimensions of the ASC, panic-fear and irritability. The LWAQ did not explain additional prescription variance, indicating that the physician's decisions were influenced by psychological reactions during asthma attacks rather than between attacks. Prescription decisions were not influenced by clinic-measured respiratory function. The results show some differences with previous studies; implications for patient management are discussed.

Adaptation, Psychological↗
PubMed1992

Effects of SCH 34826, a neutral endopeptidase inhibitor, on hypoxic pulmonary vascular remodelling.

Atrial natriuretic peptide (ANP) is a potent vasodilator of hypoxia constricted pulmonary vessels. Chronic infusions of ANP have been shown to limit the anatomical pulmonary vascular remodelling associated with chronic exposure to a 10% oxygen environment. SCH 34826 elevates plasma ANP by inhibition of the enzyme neutral endopeptidase EC 3.4.24.11. We administered by subcutaneous injection 90 mg/kg SCH 34826 twice daily into six male Wistar rats. Six littermate controls received 1 ml of 0.4% aqueous methyl cellulose vehicle. All animals were exposed to a 10% oxygen environment for 2 weeks. Administration of SCH 34826 caused a significant reduction in the hypoxia-induced pulmonary vascular remodelling and right ventricle hypertrophy. Neutral endopeptidase inhibition by drugs such as SCH 34826 could prove useful in conditions characterized by pulmonary hypertension and pulmonary vascular remodelling.

Analgesics↗
PubMed1992

Effect of chronic hypoxia on rat pulmonary resistance vessels: vasodilatation by atrial natriuretic peptide.

1. We have investigated the vasoreactivity of isolated pulmonary resistance vessels of rats after acclimatization to chronic hypoxia in a normobaric, hypoxic chamber. Vasoconstriction, in response to KCl and prostaglandin F2 alpha, and vasodilation, in response to atrial natriuretic peptide, were studied isometrically in a small-vessel myograph. Resting tensions were set to simulate transmural pressures of 17.5 mmHg or 35 mmHg. 2. There were no significant differences between intergroup internal vessel diameters or maximal contractile responses to either agonist. Both control and chronically hypoxic vessels generated significantly greater active contractions at 35 mmHg than at 17.5 mmHg. There were significant positive correlations between vessel diameter and maximum contractility for both control and chronically hypoxic vessels, but when contraction was expressed as equivalent transmural pressure no correlation existed. 3. There was a significant increase in potency (as measured by the concentration necessary to produce 50% of the maximum response) of KCl in chronically hypoxic vessels compared with control vessels at 35 mmHg, but not at 17.5 mmHg. In contrast, the potency of prostaglandin F2 alpha was significantly increased in chronically hypoxic vessels at 17.5 mmHg, but not at 35 mmHg. Thus the change in contractile responses of vessels from chronically hypoxic animals, in terms of maximal response and potency, is dependent on both resting pressure and agonist used. 4. After exposure to chronic hypoxia, atrial natriuretic peptide induced significantly greater maximal relaxation of pulmonary resistance vessels at both resting pressures, but its potency was unaffected.

Animals↗
PubMed1992

Adaptation of cough reflex with different types of stimulation.

Inhalation cough challenge has become an accepted method of investigating antitussive agents. It is, therefore, important to examine the degree of tachyphylaxis seen with repeated cough challenge. In addition, different types of challenge may reveal important differences in the neuronal pathways involved in the cough reflex. Citric acid, distilled water and capsaicin were examined to determine adaptation of the cough response during acute and long-term inhalation studies in healthy subjects. To study acute tachyphylaxis two separate one minute continuous inhalation challenges (n = 13) were performed. Long-term tachyphylaxis (n = 10) was examined using citric acid and capsaicin inhalation at 10 min intervals for 40 min, and at 4 and 6 h. Cross-tachyphylaxis to citric acid and capsaicin was examined in a separate randomized crossover study (n = 10). Highly significant adaptation occurred between the first and last 10 s of the one minute challenge with citric acid (90-100%) and distilled water (74-84%), but was less pronounced with capsaicin (37-49%, at 2 microM). Cough during the whole of the second test was significantly reduced for citric acid (50%). During long-term challenge cough was attenuated over 40 min both with citric acid (100 mM, p less than 0.05; 300 mM, p less than 0.001; 1 M, p less than 0.001) and with capsaicin (3 microM, p less than 0.01; 10, 30, 100 microM, p less than 0.001 each). With higher doses, tachyphylaxis was still present at 180 min with both citric acid (300 mM, p less than 0.05) and capsaicin (100 microM, p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1991

Atrial natriuretic peptide-induced relaxation of pre-constricted isolated rat perfused lungs: a comparison in control and hypoxia-adapted animals.

1. To further understand the vasodilator actions of atrial natriuretic peptide and its role in hypoxic pulmonary hypertension, we studied the effects of atrial natriuretic peptide in the isolated perfused rat lung during normoxic ventilation and after elevation of pulmonary artery pressure by either hypoxic ventilation or infusion of prostaglandin F2 alpha. Control animals were compared with littermates that had become adapted to a 10% O2 environment for 3 weeks. Atrial natriuretic peptide was compared with atriopeptin I and atriopeptin III in order to study its structure-activity relationship. 2. Five experiments, each involving six control and six chronically hypoxic rats, were performed. During normoxic ventilation, atrial natriuretic peptide (30 ng-3 micrograms) produced a dose-dependent reduction in pulmonary artery pressure in chronically hypoxic rats, but had no action in the control animals. 3. Atrial natriuretic peptide dose-dependently abolished hypoxic pulmonary vasoconstriction to a greater extent in chronically hypoxic rats (EC50 98 ng) than in control rats (EC50 298 ng; P less than 0.001). Bolus atrial natriuretic peptide (100 ng) produced a plasma concentration of 22.6 pmol/l at 1 min, which is within the pathophysiological range. Initial plasma atrial natriuretic peptide levels were 9.4 pmol/l in control animals and 27.4 pmol/l in chronically hypoxic rats. 4. Chronically hypoxic rats were more sensitive to atriopeptin I, atriopeptin III and atrial natriuretic peptide than were the control rats (P less than 0.05). Atrial natriuretic peptide and atriopeptin III were equipotent and were 10 times more potent than atriopeptide I in both groups (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Changes in atrial natriuretic peptide concentrations during intravenous saline infusion in hypoxic cor pulmonale.

BACKGROUND: The pathogenesis of oedema in hypoxic cor pulmonale is poorly understood. One possibility is a failure of atrial natriuretic peptide release, leading to salt and water retention. This hypothesis was tested by observing the response to an intravenous saline challenge in patients with and without cor pulmonale. METHODS: Plasma atrial natriuretic peptide concentrations were measured before and for three hours after an intravenous saline load (0.1 ml 2.7% saline/kg/min for 60 minutes) in 20 patients with chronic obstructive airways disease. Ten patients with cor pulmonale, as judged clinically by the presence of peripheral oedema with a previously documented increase in the jugular venous pressure or pleural effusions during an acute exacerbation of airway obstruction (mean (SE) age 67 (3) years, FEV1 0.73 (0.08) 1, arterial oxygen tension (PaO2) 6.4 (0.4) kPa, and arterial carbon dioxide tension (PaCO2) 6.7 (0.3) kPa), were compared with 10 patients with hypoxic chronic obstructive airways disease who had never had oedema (mean age 63 (1) years, FEV1 1.07 (0.09) 1, PaO2 8.6 (0.4) kPa, and PaCO2 5.3 (0.2) kPa). All patients were studied fasting and after diuretics had been stopped for three days. No supplemental oxygen was given. RESULTS: The mean four hourly urine sodium excretion was less in the patients who had oedema (27 (4.6) mmol, 13% of the intravenous load) than in those without oedema (82 (15.5) mmol, 43% of the load). Initial mean plasma atrial natriuretic peptide values were significantly higher in the patients with cor pulmonale (19.1 (1.6) compared with 10.2 (0.7) pmol/l) and the mean peak rise in atrial natriuretic peptide after the intravenous saline load had been given was 13 (8.0) pmol/l in the patients with cor pulmonale and 5.5 (2.3) pmol/l in the controls. There were no significant differences in plasma and urinary osmolality, blood pressure, or creatinine clearance between the groups. CONCLUSION: Patients with chronic obstructive airways disease and cor pulmonale have an impaired ability to excrete a hypertonic intravenous saline load despite a normal physiological release of plasma atrial natriuretic peptide.

Aged↗
PubMed1990

Atrial natriuretic peptide in primary pulmonary hypertension.

Plasma levels of atrial natriuretic peptide (ANP) were determined during cardiac catheterization in nine patients with primary pulmonary hypertension (PPH) and the effect of prostacyclin infusion via a right heart catheter studied. The role of hypoxia on the release of ANP was investigated in a control group of six normal subjects who underwent an acute hypoxic challenge. Patients showed the typical haemodynamic changes of primary pulmonary hypertension with elevation of mean (SD) pulmonary artery pressure, 71.3 (13.8) mmHg, and low cardiac index, 1.9 (0.5) l.min-1.m-2. Plasma ANP was also elevated; mean pulmonary artery plasma ANP was 96.3 (77.6) pmol.l-1 in PPH patients compared with mean venous plasma ANP of 8.9 (5.6) pmol.l-1 in normal subjects. Prostacyclin infusion in PPH patients and hypoxic challenge in normal subjects did not significantly alter plasma ANP levels. The elevated levels of ANP in PPH are due to the altered haemodynamics secondary to increased pulmonary vascular resistance and may be responsible for the lack of peripheral oedema seen in this condition.

Adult↗