Michelle McGuire

Chronic intermittent hypoxia increases haematocrit and causes right ventricular hypertrophy in the rat.

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.

Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats

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.

THE INFLUENCE OF STREPTOZOTOCIN DIABETES AND METFORMIN ON ERYTHROCYTE VOLUME AND ON THE MEMBRANE POTENTIAL AND THE CONTRACTILE CHARACTERISTICS OF THE EXTENSOR DIGITORUM LONGUS AND SOLEUS MUSCLES IN RATS

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 repolarised. 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 hyperpolarised in the presence of insulin. Diabetes caused an increase in the volume of the blood erythrocytes. This was prevented by metformin treatment.

Contractile And Electrical Properties Of Sternohyoid Muscle In Streptozotocin Diabetic Rats

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.

The influence of streptozotocin-induced diabetes and the antihyperglycaemic agent metformin on the contractile characteristics and the membrane potential of the rat diaphragm.

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.

The effects of dietary creatine supplements on the contractile properties of rat soleus and extensor digitorum longus muscles.

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 °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.

Effects of Almitrine on Diaphragm Contractile Properties in Young and Old Rats

Background: 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. Objectives: To determine the effects of almitrine on diaphragm contractile properties in young and old rats. Methods: In young and old rats, isometric contractile properties were measured in strips of isolated diaphragm muscle in physiological saline solution at 30°C with or without almitrine. Results: 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. Conclusions: Ageing negates the beneficial effects of almitrine on diaphragm muscle force and endurance.

Contractile properties of the diaphragm in creatine-fed rats.

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.

Upper airway EMG responses to acute hypoxia and asphyxia are impaired in streptozotocin-induced diabetic rats

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.