methimazole and Hypoxia

Topics: Female; Humans; Hypoxia; Infant; Male; Methimazole; Obstetric Labor, Premature; Pregnancy; Tachycardia; Tachypnea

The purpose of this study was to investigate the role of peripheral chemoreceptor activity on the hypoxic and hypercapnic ventilatory drives in rabbits with induced hypothyroidism. Experiments were carried out in control and hypothyroid rabbits. Hypothyroidism was induced by an administration of an iodide-blocker, methimazole in food (75 mg/100 g food) for ten weeks. At the end of the tenth week, triiodothyronine (T3) and thyroxine (T4) levels significantly decreased (P<0.001) while thyroid stimulating hormone (TSH) increased (P<0.001). Tidal volume (VT), respiratory frequency (f/min), ventilation minute volume (VE) and systemic arterial blood pressure (BP) were recorded during the breathing of the normoxic, hypoxic (8% O2-92% N2) and hypercapnic (6% CO2-Air) gas mixtures, in the anaesthetised rabbits of both groups. At the end of each experimental phase, PaO2, PaCO2, and pHa were measured. The same experimental procedure was repeated after peripheral chemoreceptor denervation in both groups. VT significantly decreased in some of the rabbits with hypothyroidism during the breathing of the hypoxic gas mixture (nonresponsive subgroup) (P<0.05). After chemodenervation, a decrease in VT was observed in this nonresponsive subgroup during normoxia (P<0.05). The percent decrease in VT in nonresponsive subgroup of hypothyroid rabbits after chemodenervation was lower than that of the chemodenervated control animals (P<0.01). When these rabbits with hypothyroidism were allowed to breath the hypercapnic gas mixtures, increases in VT and VE were not significant. In conclusion, although there is a decrease in peripheral chemoreceptor activity in hypothyroidism, it does not seem to be the only cause of decrease in ventilatory drive during hypoxia and hypercapnia.

Topics: Animals; Antithyroid Agents; Chemoreceptor Cells; Denervation; Female; Hypercapnia; Hypothyroidism; Hypoxia; Male; Methimazole; Rabbits; Respiration

Topics: Animals; Bicarbonates; Carbon Dioxide; Carbonic Anhydrases; Carotid Body; Cats; Hypoxia; In Vitro Techniques; Methimazole; Partial Pressure

The influence of thyroid hormone in thermogenesis of animals adapting to high altitude for different periods were studied in white rats. The adaptation to high altitude hypoxia decreased reaction of the organism to cold. The antithyroid injection of mercazolil potentiated the hypoxia action in cold thermogenesis and lowered sharply the body temperature stability in cooling. The analogous injection of triiodthyronine reduced the hypoxia influence on the thermogenesis and increased the contribution of the contractile heat production in the thermoregulative metabolism. The data suggest that one of the reasons of the low heat effect of the muscle contraction in adaptation to hypoxia may be the functional weakening of the thyroid gland.

Topics: Adaptation, Physiological; Altitude; Animals; Antithyroid Agents; Body Temperature Regulation; Hypoxia; Male; Methimazole; Muscles; Oxygen Consumption; Rats; Temperature; Thyroid Hormones; Triiodothyronine

Extrathyroidal monodeiodination of l-thyroxine (T(4)) is the principal source of l-triiodothyronine (T(3)) and l-reverse-triiodothyronine (rT(3)) production. To define some of the cellular factors involved, we examined T(3) and rT(3) generation from added nonradioactive T(4) in human polymorphonuclear leukocytes, using radioimmunoassays to quantify the T(3) and rT(3) generated. Under optimum incubation conditions which included a pH of 6.5 in sucrose-acetate buffer, the presence of dithiothreitol as a sulfhydryl-group protector, and incubation in an hypoxic atmosphere, significant net generation of T(3) and rT(3) was observed. Of the several subcellular fractions studied, the particulate fraction obtained by centrifugation at 27,000 g was found to possess the highest T(3)- and rT(3)-generating activities per unit quantity of protein. With respect to T(3) generation from substrate T(4), the K(m) was 5 muM and the V(max) was 7.2 pmol/min per mg protein. Propylthiouracil, methimazole, and prior induction of phagocytosis inhibited both T(3) and rT(3) generation, but T(3) generation was inhibited to a greater extent. rT(3), in a concentration equimolar to that of substrate T(4), did not alter T(3) generation, but inhibited T(3) generation when the molar ratio of rT(3) to T(4) approached 10:1. Under the incubation conditions employed, particulate fractions of leukocytes obtained from five cord blood samples displayed an essentially normal relationship between T(3)- and rT(3)-generating activities, despite the distinctly divergent serum T(3) and rT(3) concentrations in these samples. From our findings, we draw the following conclusions: (a) the human polymorphonuclear leukocyte possesses the ability to generate T(3) and rT(3) from substrate T(4); (b) the T(3)- and rT(3)-generating activities are associated principally with the 27,000 g particulate fraction and display enzymic characteristics with a sulfhydryl-group requirement; (c) T(3)-generating activity appears to be more susceptible to inhibitory influences than rT(3)-generating activity; and (d) in cord blood leukocytes, the putative enzymes catalyzing T(3) and rT(3) generation appear to be functionally intact under the experimental conditions employed.

Topics: Adult; Dithiothreitol; Fetal Blood; Humans; Hypoxia; In Vitro Techniques; Infant, Newborn; Kinetics; Methimazole; Neutrophils; Phagocytosis; Propylthiouracil; Subcellular Fractions; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Altitude; Animals; Hypoxia; Methimazole; Oxygen Consumption; Propylthiouracil; Rats; Thyroid Gland