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PubMed1991

The effect of external calcium concentration on the negative inotropic action of dantrolene in isolated hyperthyroid and euthyroid heart.

The effect of altering external calcium concentration [Ca2+]o on the negative inotropic action of dantrolene was tested in Langendorff-perfused hearts from euthyroid and hyperthyroid rats. Elevated contractility was demonstrated in the hyperthyroid hearts at all the [Ca2+]o tested. At a [Ca2+]o of 1.25 mM (physiological), dantrolene (5 x 10(-5) M) significantly reduced contractility (dP/dtmax) in hyperthyroid but not in euthyroid hearts (-42% and -4% of zero-time values at 12 min perfusion, respectively). When hearts from both groups were paced at 375 beats/min, dantrolene again exerted a greater negative inotropic action in the hyperthyroid preparations, showing that the effect was not heart rate related. Elevating the [Ca2+]o did not further affect the time course of dantrolene action in hyperthyroid hearts. In euthyroid hearts, however, raising the [Ca2+]o to 2.5 and 3.75 mM caused a progressive increase in the negative inotropic action of dantrolene (-15% and -56% of zero-time values at 12 min perfusion, respectively). Our results demonstrate that dantrolene exerts a negative inotropic action which at physiological [Ca2+]o is greater in the hyperthyroid than in the euthyroid heart thus indicating that calcium handling by the myocardium is altered in the hyperthyroid state. However, dantrolene action in the rat myocardium is more complex than was at first believed; as in euthyroid hearts, its negative inotropic action appears to be increased rather than reduced by increases in [Ca2+]o.

Animals↗

PubMed1985

Trabecular bone remodeling and bone balance in hyperthyroidism.

In vivo tetracycline double-labeled iliac crest bone biopsies from 15 hyperthyroid patients were used for the reconstruction of curves describing the variation of resorption depth and formation thickness with time. The curves emerging were compared to curves reconstructed from 13 age- and sex-matched normal individuals (mean age 44 years). The median function period for resorptive cells in hyperthyroid patients (16 days) was about one-third the resorptive period in normals (51 days). No significant difference between the osteoclast-, mononuclear-, or preosteoblast-like cell resorption depths could be demonstrated between the two groups. Consequently, the median resorption rate in hyperthyroid patients (3.8 microns/day) was more than 3 times higher than the value in the control group (1.1 micron/day). Median Sigma, was shorter in the hyperthyroid group (109 days) than in the control group (151 days, P less than 0.05), as was the median initial mineralization lag time (5 and 16 days, respectively, P less than 0.01). No significant difference between the measured mean completed wall thickness (mcwT) values in the hyperthyroid groups and the control group could be demonstrated (58.1 and 60.5 micron respectively). Median initial mineralization rate in the hyperthyroid group (1.2 micron3/micron2 per day) was not significantly higher than the value calculated in the control group (0.9 micron3/micron2 per day), but median initial matrix appositional rate in hyperthyroid (4.8 microns3/micron2 per day) was 3 times higher than the value calculated for normals (1.6 micron3/micron2 per day) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Kinetics of drug action in disease states. XXXI. Effect of experimental hyperthyroidism on the hypnotic activity of a benzodiazepine (oxazepam) in rats.

This investigation was designed to determine the effect of experimental hyperthyroidism on the hypnotic activity of a benzodiazepine and on the binding characteristics of the benzodiazepine receptor complex. Rats were made hyperthyroid by subcutaneous implantation of slow release pellets containing L-thyroxine. This treatment produced the characteristic symptoms of hyperthyroidism: increased serum thyroxine concentrations, increased heart weight and body temperature, and decreased serum protein concentrations. The hyperthyroid rats and a parallel group of normal animals (with drug-free pellets implanted subcutaneously) were slowly infused intravenously with oxazepam until they lost their righting reflex. The hyperthyroid rats required a significantly larger dose of the benzodiazepine and their total serum and cerebrospinal fluid concentrations of oxazepam (but not the serum concentration of free drug and the brain concentration) at the onset of loss of the righting reflex were modestly but statistically significantly lower than those of the normal rats. The receptor density and affinity for diazepam in hyperthyroid rats were not significantly different from those of the normal animals. Hyperthyroidism apparently affects the pharmacokinetics of oxazepam but has, at best, only a small effect on the pharmacodynamics (hypnotic activity) of the drug.

Animals↗

PubMed1984

Effect of a protein-free diet on muscle protein turnover and nitrogen conservation in euthyroid and hyperthyroid rats.

Although protein turnover in skeletal muscle is increased in hyperthyroidism and decreased in hypothyroidism, a deficient protein intake tends to increase serum T3 (tri-iodothyronine) while decreasing muscle protein turnover. To determine whether this diet-induced decrease in protein turnover can occur independent of thyroid status, we have examined muscle protein turnover and nitrogen conservation in hyperthyroid rats fed on a protein-free diet. After inducing hyperthyroidism by giving 20 micrograms of T3/100g body wt. daily for 7 days, groups of euthyroid and hyperthyroid animals were divided into subgroups fed on basal and protein-free diets. Muscle protein turnover was measured by N tau-methylhistidine excretion and [14C]tyrosine infusion. Urinary nitrogen output of euthyroid and hyperthyroid animals fed on the protein-free diet was also measured. Although hyperthyroidism increased the baseline rates of muscle protein synthesis and degradation, it did not prevent a decrease in these values in response to protein depletion. Furthermore, hyperthyroid rats showed greatly decreased nitrogen excretion in response to the protein-free diet, although not to values for euthyroid rats. These findings suggest that protein depletion made the experimental animals less responsive to the protein-catabolic effects of T3.

Animals↗

PubMed1989

Brain chemiluminescence and oxidative stress in hyperthyroid rats.

Newborn Wistar rats were made hyperthyroid by injection of tri-iodothyronine and assayed for survival, brain oxygen uptake, brain chemiluminescence and activity of antioxidant enzymes. Brain chemiluminescence was measured (1) by removing the parietal bones or (2) through the translucid parietal bones. Control animals showed a brain chemiluminescence of 130 +/- 12 c.p.s./cm2 and 99 +/- 10 c.p.s./cm2 for procedures (1) and (2) respectively. Hyperthyroid rats showed increases in the spontaneous brain photoemission of 46 and 70% compared with controls, measured by procedures 1 and 2 respectively. The hyperthyroid state did not modify the oxygen-dependent chemiluminescence of brain homogenates. The hyperthyroid animals showed a 30% increase in the oxygen uptake of brain slices and a dramatic shortening of life-span to about 16 weeks. Superoxide dismutase (the Cu-Zn enzyme), catalase and Se-dependent glutathione peroxidase activities of brain homogenates were increased by 18, 36 and 30% respectively in the hyperthyroid animals. Isolated brain mitochondria produced 0.18-0.20 nmol of H2O2/min per mg of protein in state 4 in the presence of succinate as substrate. No difference was observed between control and hyperthyroid animals. It is concluded that hyperthyroidism leads to hypermetabolism and oxidative stress in the brain. The increased levels of oxygen and peroxyl radicals may contribute to premature ageing in these animals.

Animals↗

PubMed1992

Amelioration of some metabolic effects produced by hyperthyroidism in late pregnant rats and their fetuses. Effects on lipids and proteins.

We have studied the effect of 40-45 days administration of 1 mg/kg thyroxine on protein and lipid metabolism in liver, heart, lungs, kidneys and adrenal glands of virgin and 21-day pregnant rats and their fetuses and placentae. The chronic administration of thyroid hormone produced significant increases in serum T3 and T4 in both groups as well as in organ weights and protein concentrations in virgin rats, but much smaller modifications in pregnant ones. Hyperthyroidism decreased the weight of fetal livers and increased that of placentae; protein content was increased in all fetal organs. Hyperthyroidism induced increases in phospholipid concentrations in all the organs and in total lipids only in liver and heart of adult rats, which were not counteracted by pregnancy. Pregnant rats had increases in total lipids in liver and kidneys and in adrenal phospholipids. In hyperthyroid fetuses there was an increase in hepatic total lipids and no changes in phospholipids. Hepatic lipogenesis (measured by in vivo incorporation of 3H2O into lipids) was increased by hyperthyroidism in virgin and pregnant rats, but the increase was significantly smaller in the pregnant hyperthyroid rats compared with the virgin ones. Fetal lipogenesis in liver and lung was not changed. In addition, an increase was observed in lipogenic enzyme (fatty acid synthetase and glucose-6-phosphate dehydrogenase) activities in hyperthyroid virgin rats which was prevented by pregnancy. In fetuses only pulmonary glucose-6-phosphate dehydrogenase was increased when expressed in terms of tissue weight. Our results indicate that the metabolic effect of hyperthyroidism is attenuated in pregnant rats and their fetuses, when compared with adult virgin rats, in most of the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1982

Abnormal left ventricular function in hyperthyroidism: evidence for a possible reversible cardiomyopathy.

We assessed the effects of exercise and beta-adrenoceptor blockade on left ventricular ejection fraction (LVEF) measured by radionuclide ventriculography in nine patients with uncomplicated hyperthyroidism. Patients were studied in both the hyperthyroid and euthyroid states. The hyperthyroid state was characterized by a high LVEF at rest but--paradoxically--by a significant fall (P less than 0.01) in LVEF during exercise. At the same workload and at the same heart rate, patients had a restoration of the normal rise in LVEF during exercise when they were euthyroid. The LVEF was greater during exercise (P less than 0.02) when the patients were euthyroid than when they were hyperthyroid. Pretreatment with propranolol caused similar reductions in resting LVEF in the hyperthyroid and euthyroid states; the drug attenuated the rise in LVEF during exercise when the patients were euthyroid, but did not influence the exercise-induced reduction in LVEF in hyperthyroidism. The abnormal left ventricular function observed during exercise in hyperthyroidism suggests a reversible functional cardiomyopathy, independent of beta-adrenoceptor activation, that is presumably a direct effect of an excess in circulating thyroid hormones.

Adult↗

PubMed1977

Comparison between serum thyroxine and triiodothyronine estimation and the TRH test in the routine diagnosis of hyperthyroidism.

Serum T3 and T4 levels have been determined by a radioimmunoassay technique and the TRH test has been performed in 50 patients in whom hyperthyroidism could not be ruled out by the first clinical examination alone. Each patient was then further evaluated in order to establish the state of the thyroid function. The extent to which the determination of T3 or T4 could replace the TRH test in the routine diagnosis of hyperthyroisism was evaluated. The results showed that 26 of the 50 patients had normal thyroid function and 24 had hyperthyroidism. No patient in the normal groups and all but one in the hyperthyroid group had T3 levels above the upper normal limit (2 S.D.). Two of the patients in the normal group and 19 in the hyperthyroid group had T4 levels above the upper normal limit (2 S.D.). Twenty of the patients in the normal group showed a normal TSH response to TRH (increment is greater than 3.0 micronU/ml); the remaining 6 showed an impaired or absent response. Twenty of the hyperthyroid patients had no response and four had a slightly positive response to TRH. No hyperthyroid patient had a TSH response exceeding 3.0 micronU/ml. It is concluded that the determination of T3 is superior to both the determination of T4 and the TRH test for the laboratory discrimination between eu- and hyperthyroidism.

Adult↗

PubMed1992

Serum levels of free and bound testosterone in hyperthyroidism.

OBJECTIVE: The aim of this study was to improve knowledge about the relationships between free and bound forms of testosterone in serum and the major testosterone-binding proteins during hyperthyroidism. DESIGN: Nine men and 11 women were studied when hyperthyroid due to Graves' disease and again after at least 3 months of euthyroidism. MEASUREMENTS: The serum concentrations of free T3, free T4, TSH, sex hormone-binding globulin (SHBG), LH, progesterone and free, non-SHBG bound and total testosterone were determined. RESULTS: For both sexes, hyperthyroidism was associated with significant elevations of the mean total testosterone and sex hormone-binding globulin (SHBG) levels and significant depressions of the mean percentage and concentration of non-SHBG-bound testosterone and the mean percentage of free testosterone. For women, the mean free testosterone concentration was significantly lower during hyperthyroidism than during euthyroidism; no significant difference in mean free testosterone concentration was observed between hyperthyroid and euthyroid men. When the experimentally derived data were analysed according to a model based on the binding constants of testosterone with SHBG and albumin, the simulated results for each patient when hyperthyroid and euthyroid paralleled the actual results. However, the model consistently overestimated the actual amounts of non-SHBG-bound testosterone. There was a significant correlation between SHBG concentration and the severity of thyrotoxicosis as measured by the change in thyroid hormone levels between euthyroidism and hyperthyroidism. CONCLUSIONS: Our results support the following pathogenetic sequence: thyrotoxicosis leads to a rise in serum SHBG concentration which is accompanied by an increase in testosterone concentration, a fall in the concentration of non-SHBG-bound testosterone and little or no change in the concentration of free testosterone.

Adolescent↗

PubMed1995

Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?

OBJECTIVE: The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroidism led us to perform a study in order to compare a fixed dose regime comprising doses of 185 370 or 555 MBq based on gland size assessment by palpation only, with a calculated 131I dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24-hour 131I uptake determination. DESIGN: Prospective randomized study. PATIENTS: Two hundred and twenty-one consecutive hyperthyroid patients referred for 131I treatment. Four Patients who died for reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remaining 163 patients (143 women) were studied, divided into subgroups according to the type of gland. They all received antithyroid drugs prior to 131I treatment and this was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS: Thyroid function variables were determined approximately 2 weeks before 131I treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to 131I therapy the size of the thyroid gland was determined by ultrasound and a 24-hour uptake of 131I was carried out. Thyroid volume was also estimated 12 months after 131I therapy in 78 of the 163 patients. Twelve months after the initial 131I dose patients could be classified as euthyroid, hyperthyroid or hypothyroid. RESULTS: Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthyroid. Seven of 78 (9%) in the calculated dose group and 6 out of 85 (7%, NS) in the fixed dose group were classified as permanently hypothyroid. Finally, 39 of 78 (50%) in the calculated dose group and 49 of 85 (58%, NS) in the fixed group were euthyroid at 12 months after 131I treatment. One year after 131I therapy thyroid volume was reduced from 59.3 +/- 9.2 (mean +/- SEM) to 36.2 +/- 6.6 ml (average reduction 39%) in the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6 +/- 6.1 to 41.17 +/- 4.7 ml (average reduction 32%) (P < 0.001). CONCLUSIONS: A semiquantitative approach is probably as good as the more elaborately calculated radioiodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.

Adult↗

PubMed1989

Electrophysiological abnormalities and enhanced reperfusion arrhythmias in the isolated hearts of hyperthyroid rats.

1. The influence of hyperthyroidism on electrophysiological characteristics and on reperfusion arrhythmias was examined in rat hearts. 2. Electrophysiological studies were performed with glass microelectrodes, and the experiments on reperfusion arrhythmias were done in isolated perfused hearts. 3. Ventricular muscle from hyperthyroid rats was more prone than that from euthyroid rats to develop triggered activity under conditions believed to cause myoplasmic Ca2+ overload. 4. The severity of reperfusion arrhythmias was significantly enhanced in hyperthyroid preparations as compared with euthyroid ones. 5. The enhanced reperfusion arrhythmias in hyperthyroid rats were significantly reduced by propranolol (3 x 10(-7) M), lignocaine (1 x 10(-5) M) and verapamil (3 x 10(-8) M), but not by nadolol (3 x 10(-7) M) or prazosin (3 x 10(-7) M). 6. These results suggest that increased heart rate due to hyperthyroidism and responses mediated via either alpha- or beta-adrenoceptors were not dominant causes of enhanced reperfusion arrhythmias in hyperthyroid hearts. 7. The increased tendency to develop triggered activity which was observed in the electrophysiological study, may be one possible explanation of enhanced reperfusion arrhythmias in hyperthyroid hearts.

Action Potentials↗

PubMed1978

Thyroid function tests in elderly hyperthyroid patients.

Several tests of thyroid function were performed in 35 hyperthyroid patients over the age of 65 (elderly). The results were compared to those of similar tests in 48 hyperthyroid patients under the age of 65 (young). Total serum thyroxine (T4) was within the normal range in 14 percent of the elderly and 11 percent of the young hyperthyroid patients. The free thyroxine index (FTI) was within the normal range in 11 percent of both groups. The triiodothyronine uptake (T3U) proved to be a poor test in both groups. Although elevation of the triiodothyronine (T3) level allowed a diagnosis of "T3-toxicosis" in 2 elderly and 3 young hyperthyroid patients, the T3 level was normal in 34 percent of the elderly and 13 percent of the young subjects. Correction of the T3 range for age reduced the number of normal T3 values to 12.5 percent in the elderly hyperthyroid patients. The 24-hour uptake of radioactive iodine was normal in 12 percent of the young hyperthyroid patients, 27 percent of the elderly patients with Graves' disease, and 70 percent of the elderly patients with toxic nodular goiter, despite recent readjustment of the normal range for the test. It is concluded that the diagnosis of hyperthyroidism in the elderly may be difficult and that no single test can be relied upon to exclude the diagnosis.

Adult↗

PubMed1985

The effect of age on blood pressure in hyperthyroidism.

To better define the effect of age on blood pressure in patients with hyperthyroidism, the blood pressures of 321 patients with hyperthyroidism were compared with those of 324 euthyroid controls. Subjects were divided into four age groups by decade from 20 to 59 years. The systolic, but not diastolic, blood pressure in the patients with hyperthyroidism was significantly higher in all age groups. Among the euthyroid controls, the systolic blood pressure increased with age. However, no age-related increase was apparent among the hyperthyroid patients because of the relatively high systolic blood pressure in young patients. Effective antithyroid treatment reduced the systolic blood pressure significantly in hyperthyroid patients. The reduction of systolic blood pressure was greater in the younger hyperthyroid patients than that in the older ones, so that an age-related increase in systolic blood pressure was present after a euthyroid state had been achieved. These results provide evidence against the report that in hyperthyroidism, hypertension tends to occur in older patients, and suggest that the effect of excessive thyroid hormone on the systolic blood pressure may differ according to age.

Adult↗

PubMedDate not supplied

Hypertension in cats with chronic renal failure or hyperthyroidism.

The Doppler ultrasonic recording technique was used to measure systolic and diastolic blood pressures indirectly in 28 cats with naturally occurring renal failure, 39 cats with hyperthyroidism, and 33 clinically normal cats. The mean systolic and diastolic blood pressures in the normal cats were 118.4 +/- 10.6 mm Hg and 83.8 +/- 12.2 mm Hg, respectively. In the cats with chronic renal failure, both the systolic (146.6 +/- 25.4 mm Hg) and diastolic (96.6 +/- 15.2 mm Hg) blood pressures were significantly higher (P less than 0.0001 and P less than 0.01, respectively) than in the normal cats. Elevations in systolic and/or diastolic blood pressure were recorded in 17 (61%) of the 28 cats with chronic renal failure. In the 39 untreated hyperthyroid cats, both the mean systolic (167.9 +/- 28.9 mm Hg) and diastolic (111.6 +/- 21.5 mm Hg) pressures also were significantly higher (P less than 0.0001) than normal. Increased systolic and/or diastolic blood pressure was recorded in 34 (87%) of the 39 hyperthyroid cats. In seven cats with hyperthyroidism that were reevaluated two to four months after successful treatment of the hyperthyroid state, there was a significant fall in mean systolic pressure (P less than 0.05) from a pretreatment value of 159.5 +/- 15.4 mm Hg to a posttreatment value of 132.0 +/- 1.62 mm Hg. Overall, the results of this study indicate that mild to moderate hypertension is common in cats with chronic renal failure and in cats with untreated hyperthyroidism. In addition, the hypertension appears to be reversible following successful treatment of the hyperthyroid state.

Animals↗

PubMed1982

Altered developmental changes of neuromuscular junction in hypo- and hyperthyroid rats.

1. Effects of thyroid hormone on the development of neuromuscular junctions (n.m.j.s.) were investigated electrophysiologically in the diaphragms (sternal region) of normal, hypo- and hyperthyroid rats from the age of birth (day 0) to day 35.2. Hypothyroidism in new-born rats was induced either by daily administration of propylthiouracil to mothers or by subcutaneous injection of 150 muCi (131)I on day 1. Hyperthyroidism was induced by daily injection of thyroxine.3. In normal rats up to day 10, muscle fibres were innervated polyneuronally. By day 20, multiple innervation was eliminated and muscle fibres received only a single input. In hypothyroid rats elimination of polyneuronal innervation was retarded by 5-8 days, while in hyperthyroid rats the elimination was accelerated by 2-3 days.4. The frequency of miniature end-plate potentials (m.e.p.p.s) in normal rats increased from one per 40 sec on days 0-5 to 1/sec on days 25-35. The m.e.p.p. frequency in hypothyroid rats was 25-65% of that in normal rats of the same age. In hyperthyroid rats the m.e.p.p. frequency was normal up to day 18 but subnormal afterwards. The duration of m.e.p.p. measured on day 22-23 was slower in hypothyroid rats and faster in hyperthyroid rats, relative to m.e.p.ps in normal rats.5. The sensitivity to acetylcholine (ACh) at extrajunctional regions in normal rats was about 100 mV/nC at birth and declined to 1 mV/nC by day 26. In hypothyroid rats, the ACh sensitivity was as high as 30 mV/nC on day 26; in hyperthyroid rats, ACh sensitivity on day 26 was undetectable.6. With pairs of nerve stimuli (applied at a 50 msec interval), the second end-plate potential was facilitated until day 10 and depressed after day 16 in normal rats. This shift from facilitation to depression during development was not altered in either hypo-or hyperthyroid rats.7. It is concluded that the lack and excess of thyroid hormone retards and facilitates the development of n.m.j.s. respectively. Possible mechanisms for this altered development are discussed.

Acetylcholine↗

PubMed1979

Effect of hypoxia on mechanical properties of hyperthyroid cat papillary muscle.

It has been previously established that hyperthyroid myocardium exhibits increased performance under well-oxygenated conditions. To date, it is not known whether hyperthyroid cardiac muscle can maintain this increased performance during hypoxia. The responses of isolated right ventricular papillary muscles from hyperthyroid and euthyroid kittens to hypoxia were compared under isometric conditions at 31 degrees C. Under well-oxygenated conditions, the hyperthyroid cardiac muscle exhibited both an increased contractility and an accelerated rate of relaxation. A similar degree of acute hypoxic stress for 15 min resulted in a greater decrease in contractility in the hyperthyroid compared with the euthyroid papillary muscle as indicated by a greater fall in both peak tension development (2.2 +/- 0.25 from 4.2 +/- 0.2 vs. 0.9 +/- 0.15 from 3.2 +/- 0.4 g/mm2, P less than 0.01) and +dT/dt (12.9 +/- 2.3 from 25 +/- 3 vs. 4.0 +/- 0.6 from 14 +/- 1 g-s-1-mm-2, P less than 0.01). In addition, compared with the euthyroid data, hypoxia resulted in impaired myocardial relaxation in the hyperthyroid cardiac muscle. Thus, the hyperthyroid compared with the euthyroid papillary muscle exhibits both a greater decrease in contractility and an impairment of myocardial relaxation during hypoxia, indicating a greater susceptibility to a given hypoxic stress.

Animals↗

PubMed1995

Effects of hyperthyroidism on muscle blood flow during exercise in rats.

Hyperthyroidism is associated with exercise intolerance. Previous research, however, has shown that cardiac output is either normal or enhanced during exercise in the hyperthyroid state. We therefore hypothesized that blood flow to working skeletal muscle is augmented in hyperthyroid animals during in vivo submaximal exercise and, consequently, that noncardiovascular factors are responsible for intolerance to exercise. To test this hypothesis, rats were made hyperthyroid (Hyper) over 6-12 wk with injections of triiodothyronine (300 micrograms/kg). Hyperthyroidism was evidenced by left ventricular hypertrophy [euthyroid (Eut), 2.12 +/- 0.05 mg/g body wt; Hyper, 2.78 +/- 0.06; P < 0.005], 25-60% increases in citrate synthase activities in Hyper hindlimb muscles over those of Eut rats, and higher preexercise heart rates (Eut, 415 +/- 18 beats/min; Hyper, 479 +/- 19; P < 0.025). Regional blood flows were determined by the radiolabeled microsphere method, preexercise, and at 1-2 min of treadmill running at 15 m/min (0% grade). Total hindlimb muscle blood flow preexercise was unaffected (Eut, 31 +/- 4 ml.min-1.(100) g-1, n = 11; Hyper, 40 +/- 6, n = 9; not significant) but was higher (P < 0.025) in Hyper (127 +/- 17, n = 9) compared with Eut (72 +/- 11, n = 9) during treadmill running. During exercise, flows to individual muscles and muscle sections were approximately 50-150% higher in Hyper compared with Eut rats. Visceral blood flows were largely similar between groups. These findings indicate that hyperthyroidism is associated with augmented blood flow to skeletal muscle during submaximal exercise. Thus hypoperfusion of skeletal muscle does not account for the poor exercise tolerance characteristic of hyperthyroidism.

Animals↗

PubMed1987

Effects of beta-blocking agents on urinary excretion of 3-methylhistidine during experimental hyperthyroidism in rats.

Beta-blocking agents are increasingly used as preoperative treatment of hyperthyroid patients. Relatively little is known about the effects of these drugs on metabolic alterations in hyperthyroidism. The aim of this investigation was to study the effects of two different beta-blocking agents on the urinary excretion of 3-methylhistidine (3-MH) during experimental hyperthyroidism in rats. Experimental hyperthyroidism was induced by daily intraperitoneal injections of triiodothyronine (T3; 100 micrograms/100 g body weight) for 3 days. Control animals were injected with corresponding volumes of solvent. Groups of rats received food enriched with metoprolol (8.8 mmol/kg of diet) or propranolol (3.3 mmol/kg of diet) or food without additions. Urinary 3-MH excretion was increased by about 40% during experimental hyperthyroidism. A similar increase of 3-MH excretion was found in animals receiving T3 + metoprolol, whereas the excretion of 3-MH was reduced to control level in hyperthyroid rats receiving propranolol. No effects of metoprolol or propranolol on 3-MH excretion were found in control animals. Although the source of 3-MH cannot be exactly defined, the present results indicate that increased proteolysis in skeletal muscle and/or other tissues during experimental hyperthyroidism was reduced by propranolol.

Adrenergic beta-Antagonists↗