Biomedical subjects

N MacFarlane

Publications and source records attributed to N MacFarlane.

8 recordsLinked to original sources

PubMed1997

Catecholamines contribute to exertional dyspnoea and to the ventilatory response to exercise in normal humans.

BACKGROUND: Exogenous catecholamine administration in humans stimulates ventilation. The present study was designed to investigate whether increased endogenous catecholamine release influences objective measures of ventilation and subjective measures of breathlessness in normal subjects. METHODS: Yohimbine, a pre-synaptic alpha 2 adrenoceptor antagonist, or placebo was administered to 10 normal male subjects in a double-blind cross-over fashion. Ventilation and metabolic gas exchange were measured during steady state exercise at 60% of previously determined maximal oxygen consumption. Venous lactate and noradrenaline were measured during exercise. Subjects' sensation of breathlessness and fatigue were recorded using visual analogue scales. RESULTS: Plasma noradrenaline was higher following yohimbine administration (at 6 min exercise; 4.58 +/- 0.56 nmol.l-1 vs 8.74 +/- 1.53; P < 0.05). Oxygen consumption was unchanged, but ventilation was greater throughout exercise following yohimbine. The sensation of exertion was greater following yohimbine, and at any given level of ventilation, the sensation of exertion was greater. CONCLUSIONS: Yohimbine administration causes increased noradrenaline release. This is associated with an increased ventilatory response and an increase in the sensation of exertion during steady state exercise. An increase in circulating noradrenaline might be a mechanism for both increased ventilation and pathological conditions of breathlessness such as chronic heart failure.

Adrenergic alpha-Antagonists↗

PubMed1994

Cardiorespiratory and symptomatic variables during maximal and submaximal exercise in men with stable effort angina: a comparison of atenolol and celiprolol.

Celiprolol is a novel beta 1 selective adrenoreceptor blocker with partial beta 2 agonism and direct vasodilator activity. These ancillary properties may reduce symptomatic breathlessness and fatigue and modify respiration during exercise. To test this hypothesis 20 men with stable effort angina were enrolled in a double-blind crossover study to investigate the effects of atenolol 100 mg once daily (A) and celiprolol 400 mg once daily (C) on cardiorespiratory and symptomatic variables during maximal and submaximal exercise. Total exercise time on a modified Bruce protocol was similar on both treatments: C12.5 min, A 13.1 min. During steady state submaximal exercise at 60-75% (mean 68%) of maximum work capacity, minute ventilation (C33.81 min-1, A 33.51 min-1), oxygen uptake (C14.6 ml.kg-1.min-1, A15.1 ml.kg-1.min-1), respiratory exchange ratio (C 0.89, A 0.87), ratio of VE/VCO2 (C 33.6, A 33.4), ratio of VE/VO2 (C 2.34, A 2.72), Borg perceived exertion score (C 11.2, A 10.9) and visual analogue scores for breathlessness (C 29.5, A 25.9) and muscle fatigue (C 28.9, A 26.0) were all similar on both treatments. At maximal exercise capacity on the modified Bruce protocol, minute ventilation (C 58.31 min-1, A 60.41 min-1), oxygen uptake (C 21.3 ml.kg-1.min-1, A 21.7 ml.kg-1.min-1), respiratory exchange ratio (C 1.02, A.1.05), ratio VE/VCO2 (C 34.8, A 35.9), and ratio VE/VO2 (C 2.80, A 2.83) were also similar on both drugs. Over a 10 day period anginal attacks (C 10.1 +/- 10.4, A 5.4 +/- 5.9) and sublingual GTN use (C 5.9 +/- 10.3, A 4.4 +/- 9.8) were both more frequent on celiprolol).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Analysis of novel imidazoles from isolated perfused rabbit heart by two high-performance liquid chromatographic methods.

The paper reports two analytical high-performance liquid chromatographic methods to detect and quantify cardiac-derived histidyl derivatives. Method A relies on relative hydrophobicities as a basis of separation. Method B is an ion-pairing method in which the compounds are eluted in an entirely different order. Fractions collected from method A have been co-eluted in admixture in method B with authentic reference compounds. Thus the existence of the following imidazole ring-containing compounds derived from heart have been confirmed: N-acetylhistidine, N-acetyl-1-methylhistidine, N-acetylcarnosine, N-acetylhomocarnosine, homocarnosine, anserine, carnosine, balenine. Compounds were found in both tissue samples and perfusates.

Animals↗

PubMed1992

Pulmonary extraction and left atrial secretion of atrial natriuretic factor during cardiopulmonary bypass surgery.

We have investigated the role of the lungs in the extraction of atrial natriuretic factor (ANF) by measuring plasma levels in samples taken from the central circulation in 12 patients (mean age 59 years; range 43 to 68) undergoing cardiac surgery. We also investigated the effects of cardiopulmonary bypass on ANF levels. ANF levels (mean +/- SD) were lower in pulmonary venous samples (41 +/- 20 pg/ml) than in pulmonary arterial samples (54 +/- 18 pg/ml; p less than 0.001), demonstrating 24% extraction of ANF by the lungs. Both left atrial (47 +/- 23 pg/ml) and systemic arterial levels (52 +/- 22 pg/ml) were higher than pulmonary venous levels (both p less than 0.05), indicating secretion of ANF into the left side of the heart. During cardiopulmonary bypass, plasma ANF concentration fell from 68 +/- 23 pg/ml before aortic cross-clamping to 35 +/- 13 pg/ml 10 minutes after and 28 +/- 9 40 minutes after the application of clamps (both p less than 0.001). A rebound rise to 122 +/- 33 pg/ml followed the release of the clamp (p less than 0.001). This study demonstrates that ANF is extracted by the lungs and secreted directly into the left side of the heart. The considerable fall in plasma levels that was observed during aortic cross-clamping might contribute to the neurohumoral activation and increased peripheral resistance observed after prolonged cardiopulmonary bypass and to the risk of renal ischemic injury.

Atrial Function, Left↗

PubMed1991

Synergism of histidyl dipeptides as antioxidants.

Histidyl dipeptides such as carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-amino-butyryl-L-histidine) are reported at millimolar concentrations in several mammalian tissues (O'Dowd et al., 1988; House et al., 1989), but their precise physiological function, or functions, is uncertain. These compounds are known to be potent buffers at physiological pH (Davey, 1960). They are also able to restore functional capacity to fatigued muscle preparations, stimulate some glycolytic enzymes and maintain coupling between mitochondrial oxidation and phosphorylation (Severin, 1964). Histidyl dipeptides may also have antioxidant activity, though this finding is controversial. For example, Aruoma et al. have argued that these compounds, individually, are unable to scavenge superoxide (O2-.), hydrogen peroxide (H2O2) or hypochlorous acid (HOCl) at rates which could offer antioxidant protection in vivo. Since there is a range of these histidyl dipeptides within mammalian tissue we have investigated possible synergism between them in respect of antioxidant activity. Our results show that combining histidine-containing compounds at near physiological concentrations results in synergistic antioxidant activity.

Anserine↗

PubMed1991

A comparative study of left ventricular structure and function in elite athletes.

Adaptations to left ventricular (LV) structure and function appear to be dependent on the type, intensity and duration of exercise training. We therefore studied two clearly defined groups of elite athletes, by M-mode and Doppler echocardiography, with a group of inactive individuals as controls. All groups were age matched. Group 1 comprised ten elite endurance athletes with maximal oxygen consumption (VO2 max) of 74.7 +/- 1.43 (mean +/- SEM). Group 2 consisted of ten elite weightlifters with VO2 max 45.3 +/- 2.00. Group 3 comprised of ten inactive individuals with VO2 max 44.5 +/- 2.13. Left ventricular end diastolic dimension was significantly higher in group 1 (5.72 +/- 0.07) than in groups 2 or 3 (5.29 +/- 0.09 and 5.19 +/- 0.09 respectively, p less than 0.001). Left ventricular mass index was significantly higher in groups 1 and 2 (156.4 +/- 5.97 and 138.6 +/- 7.27 respectively) than in group 3 (104.1 +/- 3.16 p less than 0.001). Percentage fractional shortening was used as an index of systolic function and no significant difference was found between groups. Doppler E:A ratio was taken as an index of diastolic function and was found to be significantly elevated in group 1 at rest (3.37 +/- 0.24) compared with 2.38 +/- 0.16 and 1.99 +/- 0.10 in groups 2 and 3 respectively (p less than 0.003). On exercise, the E:A ratio in group 1 was significantly higher than in group 3 (1.95 +/- 0.14 and 1.23 +/- 0.05 respectively p less than 0.001), and tended to be higher than group 2 (1.68 +/- 0.15 p = ns). These data show that both modes of intense training produce left ventricular hypertrophy. Diastolic function is not impaired in the athletes and may be augmented in the endurance athletes.

Adolescent↗

PubMed1988

Haemophilus influenzae meningitis in Manitoba and the Keewatin District, NWT: potential for mass vaccination.

A community-based surveillance study of all central nervous system infections was carried out in Manitoba and the Keewatin District, NWT, between Apr. 1, 1981, and Mar. 31, 1984. There were 201 cases of bacterial meningitis in Manitoba over the study period, 81 (40%) caused by Haemophilus influenzae; all but one isolate tested were type b (Hib). There were nine cases of H. influenzae meningitis in the Keewatin District. The overall annual incidence rate of H. influenzae meningitis in Manitoba was 2.5/100,000; for children under 5 years the rate was 32.1/100,000. For the Keewatin District the corresponding rates were 69.6/100,000 and 530/100,000. A total of 85% and 100% of the cases of H. influenzae meningitis occurred by 24 months of age in Manitoba and the Keewatin District respectively. The age at onset was earlier in native Indian children (22 cases) and Inuit children (9 cases) than in non-native children (59 cases) (p less than 0.005); thus, vaccine prevention of Hib meningitis will likely be more difficult in native Indian and Métis children. Without evaluating the increased potential of H. influenzae vaccines to prevent nonmeningitic forms of disease, we concluded that mass childhood vaccination with polyribosylribitolphosphate (PRP) vaccine is not warranted in Manitoba or the Keewatin District. Immunogenicity studies suggest that administration of conjugated Hib vaccines such as PRP-D in infancy may prevent approximately one-third to two-thirds of cases of H. influenzae meningitis; these vaccines warrant consideration for use in mass childhood vaccination programs.

Age Factors↗

PubMed1973

A kinetic study of rabbit muscle pyruvate kinase.

The paper reports a study of the kinetics of the reaction between phosphoenolpyruvate, ADP and Mg(2+) catalysed by rabbit muscle pyruvate kinase. The experimental results indicate that the reaction mechanism is equilibrium random-order in type, that the substrates and products are phosphoenolpyruvate, ADP, Mg(2+), pyruvate and MgATP, and that dead-end complexes, between pyruvate, ADP and Mg(2+), form randomly and exist in equilibrium with themselves and other substrate complexes. Values were determined for the Michaelis, dissociation and inhibition constants of the reaction and are compared with values ascertained by previous workers.

Adenosine Diphosphate↗