M McGuire

University College Dublin, Dublin, Leinster, Ireland

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Publications (31)60.55 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aerobic organisms maintain O(2) homeostasis by responding to changes in O(2) supply and demand in both short and long time domains. In this review, we introduce several specific examples of respiratory plasticity induced by chronic changes in O(2) supply (environmental hypoxia or hyperoxia) and demand (exercise-induced and temperature-induced changes in aerobic metabolism). These studies reveal that plasticity occurs throughout the respiratory system, including modifications to the gas exchanger, respiratory pigments, respiratory muscles, and the neural control systems responsible for ventilating the gas exchanger. While some of these responses appear appropriate (e.g., increases in lung surface area, blood O(2) capacity, and pulmonary ventilation in hypoxia), other responses are potentially harmful (e.g., increased muscle fatigability). Thus, it may be difficult to predict whole-animal performance based on the plasticity of a single system. Moreover, plastic responses may differ quantitatively and qualitatively at different developmental stages. Much of the current research in this field is focused on identifying the cellular and molecular mechanisms underlying respiratory plasticity. These studies suggest that a few key molecules, such as hypoxia inducible factor (HIF) and erythropoietin, may be involved in the expression of diverse forms of plasticity within and across species. Studying the various ways in which animals respond to respiratory challenges will enable a better understanding of the integrative response to chronic changes in O(2) supply and demand.
    Integrative and Comparative Biology 10/2007; 47(4):532-551. · 3.02 Impact Factor
  • Aidan Bradford, Michelle McGuire, Ken D O'Halloran
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    ABSTRACT: Obstructive sleep apnoea (OSA) is characterised by repetitive collapse of the upper airway during sleep owing to a sleep-related decrement in upper airway muscle activity with consequent failure of the pharyngeal dilator muscles to oppose the collapsing pressure that is generated by the diaphragm and accessory muscles during inspiration. The causes of upper airway obstruction during sleep are multi-factorial but there is evidence implicating intrinsic upper airway muscle function and impaired central regulation of the upper airway muscles in the pathophysiology of OSA. The condition is associated with episodic hypoxia due to recurrent apnoea. However, despite its obvious importance very little is known about the effects of episodic hypoxia on upper airway muscle function. In this review, we examine the evidence that chronic intermittent hypoxia can affect upper airway muscle structure and function and impair CNS control of the pharyngeal dilator muscles. We review the literature and discuss results from our laboratory showing that episodic hypoxia/asphyxia reduces upper airway muscle endurance and selectively impairs pharyngeal dilator EMG responses to physiological stimulation. Our observations lead us to speculate that episodic hypoxia--a consequence of periodic airway occlusion--is responsible for progression of OSA through impairment of the neural control systems that regulate upper airway patency and through altered respiratory muscle contractile function, leading to the establishment of a vicious cycle of further airway obstruction and hypoxic insult that chronically exacerbates and perpetuates the condition. We conclude that chronic intermittent hypoxia/asphyxia contributes to the pathophysiology of sleep-disordered breathing.
    Respiratory Physiology & Neurobiology 08/2005; 147(2-3):223-34. · 2.05 Impact Factor
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    ABSTRACT: Obstructive sleep apnoea (OSA) is a major clinical disorder that is characterised by multiple episodes of upper airway obstruction due to failure of the upper airway dilator muscles to maintain upper airway patency. The incidence of OSA is high in many endocrine disorders including both insulin-dependent and non-insulin-dependent diabetes but the reasons for this are not known. We wished to test the hypothesis that central respiratory motor output to the upper airway muscles is preferentially impaired in a rat model of diabetes mellitus. Sternohyoid (SH) and diaphragm (DIA) EMG activities were recorded in control and streptozotocin (STZ)-induced diabetic rats during normoxia, hypoxia (7.5% O2 in N2) and asphyxia (7.5% O2 and 3% CO2) under pentobarbitone anaesthesia. SH EMG responses to acute hypoxia and asphyxia were significantly impaired in STZ-induced diabetic rats compared to control animals (+47.1 +/- 5.7 vs. +11.7 +/- 1.9% during hypoxia in control and diabetic animals respectively and +56.5 +/- 7.9 vs. +15.7 +/- 5.0% during asphyxia). However, DIA EMG responses to hypoxia and asphyxia were not different for the two groups. We propose that the higher prevalence of OSA in diabetic patients is related to preferential impairment of cranial motor output to the dilator muscles of the upper airway in response to physiological stimuli.
    Respiratory Physiology & Neurobiology 12/2003; 138(2-3):301-8. · 2.05 Impact Factor
  • Michelle McGuire, Mary MacDermott, Aidan Bradford
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    ABSTRACT: In obstructive sleep apnea (OSA), there is intermittent upper airway (UA) collapse due to an imbalance between the collapsing force generated by the diaphragm and the stabilizing force of the UA muscles. This results in chronic intermittent asphyxia (CIA). We have previously shown that CIA affects UA muscle fatigue, but little is known about the effects of chronic hypoxia on diaphragm or on limb muscle contractile properties and structure. Rats were exposed to asphyxia and normoxia twice per minute for 8 h/d for 5 weeks to simulate the intermittent asphyxia of OSA in humans. Isometric contractile properties were determined from strips of isolated diaphragm, extensor digitorum longus (EDL), and soleus muscles in Krebs solution at 30 degrees C. EDL and soleus type 1 (slow, fatigue resistant), type 2A (fast, fatigue resistant), and type 2B (fast, fatigable) fiber distribution was determined using adenosine triphosphatase staining. CIA caused a significant increase in diaphragm, EDL, and soleus fatigue, and reduced recovery from fatigue. Most of the other contractile properties were unaffected aside from a small reduction in diaphragm half-relaxation time and EDL twitch tension and a small shift to the left in the EDL force-frequency curve. There was no change in soleus fiber-type distribution and a small increase in EDL type 2A fibers (46.1 +/- 1.2% vs 49.9 +/- 1.4%, control vs CIA [mean +/- SD]). CIA increases diaphragm, EDL, and soleus muscle fatigue. We speculate that if this also occurs in OSA, it would contribute to the pathophysiology of the condition.
    Chest 04/2003; 123(3):875-81. · 5.85 Impact Factor
  • Michelle McGuire, Mary MacDermott, Aidan Bradford
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    ABSTRACT: Obstructive sleep apnea (OSA) is caused by episodes of upper airway (UA) obstruction due to an inability of UA muscles such as the geniohyoids and sternohyoids to maintain airway patency. This results in chronic episodic hypercapnic hypoxia. Chronic continuous hypoxia and episodic hypocapnic hypoxia affect skeletal muscle structure and function, but the effects of chronic episodic hypercapnic hypoxia on UA muscle structure and function are unknown. Rats breathed air and hypercapnic hypoxic gas twice per minute for 8 h/d for 5 weeks in order to mimic the intermittent hypercapnic hypoxia of OSA in humans. Isometric contractile properties were determined using strips of isolated geniohyoid and sternohyoid muscles in physiologic saline solution at 30 degrees C. Fiber-type distribution was determined by adenosine triphosphatase staining. For both muscles, chronic episodic hypercapnic hypoxia had no significant effect on twitch or tetanic tension, twitch/tetanic tension ratio, and tension-frequency relationship. There was a significant (p < 0.05) increase in geniohyoid fatigue (50.5 +/- 6.6% vs 43.6 +/- 5.8% of initial tension), but sternohyoid fatigue was reduced (31.5 +/- 5.2% vs 37.8 +/- 6.0% of initial tension). Geniohyoid type 1 fibers were reduced and type 2B fibers increased, whereas sternohyoid muscle had an increase in type 1 and 2A fibers and a decrease in type 2B fibers. Chronic episodic hypercapnic hypoxia alters UA muscle structure and function, changes that may affect the regulation of UA patency.
    Chest 10/2002; 122(4):1400-6. · 5.85 Impact Factor
  • M McGuire, A Bradford, M MacDermott
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    ABSTRACT: 1. Creatine feeding increases the oxidative capacity of type 1 skeletal muscle fibres and, in soleus muscles, consisting mainly of type 1 fibres, increases fatigue resistance. The diaphragm contains a relatively large content of type 1 fibres and respiratory muscle fatigue is a cause of respiratory failure. The aim of the present study was to determine whether creatine supplements increase fatigue resistance in the diaphragm. 2. Rats were given creatine monohydrate (2.55 g/L) in the drinking water. After 5-6 days, isometric contractile properties were measured in strips of costal diaphragm in Krebs' solution at 30 degrees C. Measurements were also made in soleus muscle strips. Values for strips from creatine-fed rats were compared with those from control rats. 3. Creatine feeding did not increase fatigue resistance and had no effect on twitch or tetanic tension or twitch kinetics in the diaphragm. Creatine increased fatigue resistance in soleus muscles, as reported previously.
    Clinical and Experimental Pharmacology and Physiology 10/2002; 29(9):782-3. · 2.41 Impact Factor
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    ABSTRACT: Obstructive sleep apnea (OSA) is a major clinical disorder that is characterized by multiple episodes of upper airway obstruction due to the failure of the upper airway dilator muscles to maintain upper airway patency. This results in chronic intermittent asphyxia (CIA) due to repetitive apneas, but very little is known about the effects of CIA on upper airway muscle function. To test the hypothesis that CIA affects upper airway muscle activity and electromyogram (EMG) responses to acute hypoxia and asphyxia. Record upper airway EMG responses to acute hypoxia and asphyxia in control and CIA-treated rats. Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland. Sternohyoid (SH) muscle and diaphragm (DIA) muscle EMG activities were recorded in both groups during normoxia, hypoxia (7.5% O(2) in N(2)), and asphyxia (7.5% O(2) and 3% CO(2)) under pentobarbitone anesthesia. Baseline SH EMG activity was significantly elevated in the CIA-treated rats compared to the controls, whereas DIA EMG activity was similar in the two groups. In addition, CIA significantly reduced SH EMG but not DIA EMG responses to acute hypoxia and asphyxia. The elevated upper airway muscle activity associated with OSA in humans during wakefulness is due at least in part to CIA. We propose that a reduction in the response of upper airway dilator muscles to acute asphyxia following upper airway obstruction is likely to cause further asphyxic insult, leading to a vicious feed-forward cycle exacerbating the condition. Our results suggest that CIA contributes to the pathophysiology of sleep-disordered breathing.
    Chest 08/2002; 122(1):269-75. · 5.85 Impact Factor
  • M McGuire, D Cantillon, A Bradford
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    ABSTRACT: Diaphragm muscle force and fatigue are key factors in the development of respiratory failure. Almitrine is used to improve ventilatory drive and ventilation-perfusion matching in respiratory failure. Recently, it has also been shown to improve diaphragm muscle force and endurance in young rats, but it is not known if this effect persists with ageing. To determine the effects of almitrine on diaphragm contractile properties in young and old rats. In young and old rats, isometric contractile properties were measured in strips of isolated diaphragm muscle in physiological saline solution at 30 degrees C with or without almitrine. In young animals, almitrine increased twitch tension, reduced half-relaxation time and increased endurance, but had no effect on tetanic tension, contraction time or tension-frequency relationship. Ageing had no effect on endurance, but did reduce twitch and tetanic tension and contraction and half-relaxation time. Almitrine had no effect on contractile tension and kinetics, tension-frequency relationship or on endurance in the old animals. Ageing negates the beneficial effects of almitrine on diaphragm muscle force and endurance.
    Respiration 02/2002; 69(1):75-80. · 2.62 Impact Factor
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    M McGuire, A Bradford
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    ABSTRACT: Sleep-disordered breathing is associated with pulmonary hypertension and raised haematocrit. The multiple episodes of apnoea in this condition cause chronic intermittent hypoxia and hypercapnia but the effects of such blood gas changes on pulmonary pressure or haematocrit are unknown. The present investigation tests the hypothesis that chronic intermittent hypercapnic hypoxia causes increased pulmonary arterial pressure and erythropoiesis. Rats were treated with alternating periods of normoxia and hypercapnic hypoxia every 30 s for 8 h per day for 5 days per week for 5 weeks, as a model of the intermittent blood gas changes which occur in sleep-disordered breathing in humans. Haematocrit, red blood cell count and haemoglobin concentration were measured each week and systemic and pulmonary arterial blood pressure and heart weight were measured after 5 weeks. In relation to control, chronic intermittent hypercapnic hypoxia caused a significant increase in systemic (104.3+/-4.7 mmHg versus 121.0+/-10.4 mmHg) and pulmonary arterial pressure (20.7+/-6.8 mmHg versus 31.3+/-7.2 mmHg), right ventricular weight (expressed as ratios) and haematocrit (45.2+/-1.0% versus 51.5+/-1.5%). It is concluded that the pulmonary hypertension and elevated haematocrit associated with sleep-disordered breathing is caused by chronic intermittent hypercapnic hypoxia.
    European Respiratory Journal 09/2001; 18(2):279-85. · 6.36 Impact Factor
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    ABSTRACT: 1. The effects of diabetes on the electrical and contractile function of skeletal muscle are variable, depending on muscle fibre type distribution. The muscles of the upper airway have a characteristic fibre distribution that differs from previously studied muscles, but the effects of diabetes on upper airway muscle function are unknown. Normally, contraction of upper airway muscles, such as the sternohyoids, dilates and/or stabilizes the upper airway, thereby preventing its collapse. Diabetes is associated with obstructive sleep apnoea in which there is collapse of the upper airway due to failure of the upper airway musculature to maintain airway patency. Therefore, the purpose of the present study was to determine the effects of diabetes on the electrical and contractile characteristics of upper airway muscle. 2. Rats were treated with vehicle (sodium citrate buffer; pH 4.5) or with streptozotocin to induce diabetes, confirmed by the presence of hyperglycaemia, and the contractile and electrical properties of the sternohyoid were compared in these two groups. Isometric contractile properties and membrane potentials were determined in isolated sternohyoid muscles in physiological saline solution at 25 degrees C. 3. Streptozotocin had no effect on sternohyoid muscle fatigue, the tension-frequency relationship or membrane potentials, but did increase contraction time, half-relaxation time, twitch tension and tetanic tension. 4. Streptozotocin-induced diabetes has no effect on sternohyoid muscle fatigue or the tension-frequency relationship, but does reduce contractile kinetics and increases force generation. These effects are not due to changes in resting membrane potential. These data are evidence that the association of sleep apnoea and diabetes is not due to effects on upper airway muscle contractile properties.
    Clinical and Experimental Pharmacology and Physiology 04/2001; 28(3):184-7. · 2.41 Impact Factor
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    M McGuire, A Bradford, M MacDermott
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    ABSTRACT: Daily creatine supplements (0.258 g kg(-1) ) were administered to adult male Wistar rats (n = 7) in the drinking water. Age matched rats (n = 6) acted as controls. After 5-6 days, contractile properties were examined in soleus and extensor digitorum longus (EDL) muscle strips in vitro at 30 degrees C. In soleus muscles, creatine supplements decreased the half-relaxation time of the isometric twitch from 53.6 +/- 4.3 ms in control muscles to 48.4 +/- 5.5 ms but had no effect on twitch or tetanic tension or on twitch contraction time. In EDL muscles twitch tension, tetanic tension, twitch contraction and half-relaxation times were all unaffected by creatine supplements. Creatine supplements increased the fatigue resistance of the soleus muscles but had no effect on that of the EDL muscles. After a 5 min low-frequency fatigue test, tension (expressed as a percentage of initial tension) was 56 +/- 3 % in control soleus muscles, whereas that in the creatine-supplemented muscles was 78 +/- 6 % (P < 0.01). In the EDL muscles, the corresponding values were 40 +/- 2 % and 41 +/- 9 %, respectively. The force potentiation which occurred in the EDL muscles during the initial 20-30 s of the fatigue test was 170 +/- 10 % of initial tension in the control muscles 24 s after the initial stimulus train but was reduced (P < 0.01) to 130 +/- 20 % in the creatine-supplemented muscles. In conclusion, soleus muscle endurance was increased by creatine supplements. EDL endurance was unaffected but force potentiation during repetitive stimulation was decreased. Experimental Physiology (2001) 86.2, 185-190.
    Experimental Physiology 03/2001; 86(2):185-90. · 2.79 Impact Factor
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    M McGuire, M MacDermott
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    ABSTRACT: The effects of streptozotocin (STZ) diabetes and the antihyperglycaemic agent metformin on the contractile characteristics of the limb skeletal muscles and on erythrocyte volume were examined in rats. After 8 weeks of diabetes, the tetanic tension of the extensor digitorum longus (EDL) muscle decreased and the half-relaxation time of the soleus muscle increased. Endurance decreased in both muscles. Metformin treatment of the diabetic rats did not prevent the development of these contractile changes. Diabetes induced depolarisation in the EDL and soleus muscles. Following exposure to insulin, both muscles repolarized. Metformin treatment of control rats induced depolarisation in the EDL and soleus muscles, but in the depolarised EDL and soleus muscles of the diabetic rats metformin treatment caused no further depolarisation. The muscles of metformin-treated control and diabetic rats hyperpolarized in the presence of insulin. Diabetes caused an increase in the volume of the blood erythrocytes. This was prevented by metformin treatment.
    Experimental Physiology 12/1999; 84(6):1051-8. · 2.79 Impact Factor
  • M McGuire, A Bradford
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    ABSTRACT: Chronic continuous hypoxia increases haematocrit and causes right ventricular hypertrophy and pulmonary hypertension. In obstructive sleep apnoea, the exposure to hypoxia is intermittent rather than continuous but the effects of chronic intermittent hypoxia on haematocrit and right ventricular mass are unclear. Wistar rats were exposed to alternating periods of hypoxia and normoxia twice per min for 8 h per day for 5 weeks in order to mimic the intermittent hypoxia of obstructive sleep apnoea in humans. Haematocrit was significantly raised at day 7, 14, 21, 28 and 35 of the treatment period. At the end of the treatment, there was a significant increase in right ventricular mass. Therefore, chronic intermittent hypoxia increases haematocrit and right heart mass. These results suggest that the raised haematocrit and pulmonary arterial pressure observed in some cases of obstructive sleep apnoea in humans may be caused by intermittent nocturnal hypoxaemia.
    Respiration Physiology 10/1999; 117(1):53-8.
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    M McGuire, M MacDermott
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    ABSTRACT: After 2 months of streptozotocin-induced diabetes in rats, the membrane potential of the diaphragm muscle when measured in vitro at 30 degrees C was unchanged but the tetanic tension, the half-relaxation time of the isometric twitch and the fatigue resistance were each reduced. Treatment of the diabetic rats with the antihyperglycaemic agent metformin prevented the decrease in half-relaxation time and the greater degree of fatigue in the diaphragms. The possibility that changes in H+ and cyclic AMP concentrations in the diabetic muscles contributed to the decreased contractile function and that metformin acted by attenuating these changes is discussed.
    Experimental Physiology 08/1998; 83(4):481-7. · 2.79 Impact Factor
  • Irish Journal of Medical Science 03/1994; 163(4):139-167. · 0.51 Impact Factor
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    ABSTRACT: We analysed 1500 consecutive fine needle aspiration cytology (FNAC) specimens to ascertain the reasons for diagnostic failure. Of 221 tumours proven malignant following open biopsy, 184 (83%) were correctly diagnosed on FNAC. Of 1082 aspirates classified 'benign', 787 (73%) underwent open biopsy and of these 33 (4%) were diagnosed malignant. All three cases of ductal carcinoma in-situ (DCIS) and eight of 16 lobular carcinomas in this study were missed using FNAC alone. Twelve of the 22 patients with invasive carcinoma not diagnosed on cytology had tumours measuring less than 1 cm diameter. Six of 1500 FNAC reports (0.4%) gave false positive diagnoses, five were classified as 'suspicious of malignancy; and one as 'frankly malignant'. The overall sensitivity was 84%, specificity 99% and positive predictive value 97%. Though these results confirm the value of FNAC as a rapid means of diagnosing most breast cancers, it it unreliable in patients with invasive carcinomas less than 1 cm in diameter and for the detection of lobular and in-situ carcinoma.
    Irish medical journal 06/1993; 86(3):100-1. · 0.51 Impact Factor
  • Irish Journal of Medical Science 09/1992; 161(10):600-619. · 0.51 Impact Factor
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    ABSTRACT: The role of combined cytohistological examination in the differentiation of benign from malignant oesophageal mucosal lesions was studied in 331 patients. Malignancy was confirmed by specimen histopathology in 58 patients. Both endoscopic biopsy and cytology were positive in 41 (71%) patients. Endoscopic biopsy alone suggested malignancy in 10 cases (17%) while cytology was positive after negative biopsy in seven (12%). Cytology yielded four false positive and 10 false negative results giving a sensitivity level of 81%, a specificity of 98% and a positive predictive value for oesophageal malignancy of 92%. Histology on the other hand yielded one false positive and seven false negative results providing a sensitivity of 87%, a specificity of 99% and a positive predictive value of 96%. No patients were left undiagnosed using both diagnostic modalities; cytology increased the diagnostic yield from 87% to 100%. Exfoliative cytology was most valuable in the diagnosis of tumours of the lower one-third of the oesophagus where seven of 31 malignancies (23%) were identified by this method alone (P less than 0.05). Neither the histological type of the tumour nor the morphological appearance was found significantly to affect the diagnostic yield (P greater than 0.05). We conclude that cytological examination should be standard practice in the investigation of oesophageal lesions.
    European Journal of Surgical Oncology 09/1992; 18(4):332-4. · 2.61 Impact Factor
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    ABSTRACT: We have analysed the accuracy of cytological examination of voided urine in a population of 265 patients presenting with suspected bladder lesions. Bladder carcinoma was confirmed by tissue histopathology in 51 patients. Of these, 42 were identified correctly by urinary cytology examination. Overall 34 patients were labelled as frankly malignant on cytology, of whom 2 were negative on final histology. 13 patients had been designated as suspicious however with 3 benign on final histological diagnosis. These data give a sensitivity for diagnosis of bladder cancer by urinary cytology of 82%, a specificity of 97%, a positive predictive value of 94%, and a negative predictive value of 96%.
    Irish Journal of Medical Science 12/1991; 160(11):352-3. · 0.51 Impact Factor
  • Irish Journal of Medical Science 06/1991; 160(7):213-236. · 0.51 Impact Factor

Publication Stats

266 Citations
60.55 Total Impact Points

Institutions

  • 2002–2003
    • University College Dublin
      • School of Mechanical and Materials Engineering
      Dublin, Leinster, Ireland
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1998–2003
    • Royal College of Surgeons in Ireland
      • Department of Anatomy
      Dublin, Leinster, Ireland
  • 1990–1993
    • Galway University Hospitals
      Gaillimh, Connaught, Ireland