Stimulation of cardiac myosin adenosine triphosphatase in thyrotoxicosis.

Morkin, Eugene

doi:10.1161/01.res.44.1.1

Cited by 56 publications

(26 citation statements)

References 52 publications

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“…It has been suggested by some investigators that thyroid hormone has a direct effect on the myocardium (22) but this has been disputed (23). In a review of the mechanism of the inotropic effects of thyroid hormone, it was suggested that it was largely dependent on altered cardiac myosin ATPase activity (24). Fink and Morkin (25) indicated that the increased contractility of the hyperthyroid heart could at least in part be accounted for by appearance of a new species of myosin with a greater actin-activated ATPase activity.…”

Section: Discussionmentioning

confidence: 99%

Role of thyroid hormone in postnatal circulatory and metabolic adjustments.

1984

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At bstract. To assess the role of the early postnatal surge in plasma thyroid hormone concentrations on cardiovascular and metabolic adaptations, we measured cardiac output, total oxygen consumption, and plasma triiodothyronine (T3) concentrations in three groups of lambs in the first 6 h after delivery. 15 fetal lambs were prepared at gestational ages of 128-129 d by placing catheters in the brachiocephalic artery, descending aorta, distal inferior vena cava, left atrium, and pulmonary artery so that measurements could be made soon after delivery. They were divided into three groups: Group I comprised five control animals; Group II consisted of five fetuses in which thyroidectomy was performed at surgery at 129 d gestation; and Group III consisted of five animals in which thyroidectomy was performed at term gestation during delivery by caesarian section, prior to severing the umbilical cord. The lambs in Group I exhibited a rapid postnatal rise in T3 concentrations, similar to that described previously, reaching a peak value of about 5 ng/ml. Although the postnatal surge in T3 concentration was arrested in Group II and III animals, Group II had no detectable plasma T3, while the Group III animals had T3 concentrations of about 0.8 ng/ml, which were within the range previously reported for term lamb fetuses. The lambs in group II showed 40-50% lower left ventricular outputs (190 vs. 297 lambs in Group II also had significantly lower heart rates (131 vs. 192 beats/min) and mean systemic arterial pressures (56 vs. 72 torr). However, there were no significant differences for any of these measurements between the Group III and Group I lambs. The reduction in cardiac output in the Group II animals were reflected in a significantly lower blood flow to the peripheral circulation, but there were no significant differences in blood flow to other organs in the three groups. These studies indicate that plasma thyroid concentrations in the 2-3 wk prior to delivery and not the increase in thyroid hormone concentrations which occur after birth are important for postnatal cardiovascular and metabolic adjustments. We speculate that lack of circulating triiodothyronine in late gestation may affect postnatal cardiovascular adaptation by modifying normal beta adrenergic receptor development.

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Section: Discussionmentioning

confidence: 99%

Role of thyroid hormone in postnatal circulatory and metabolic adjustments.

1984

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“…Flink and Morkin (4), using cyanogen bromide to cleave the polypeptide chains at methionine residues, showed the presence of a new myosin heavy chain isoenzyme in thyrotoxic rabbit hearts, which correlated with an increased actin-activated myosin MgATPase activity (5)(6)(7)(8). Hoh (9), using a technique for polyacrylamide gel electrophoresis (PAGE)' of intact native myosin in a glycerol-pyrophosphate buffer system, was able to separate three different ventricular myosin heavy chain isoenzymes (VI, V2, and V3, in order of decreasing velocity of migration) in rat heart (10).…”

Section: Introductionmentioning

confidence: 99%

Structural and Enzymatic Comparison of Human Cardiac Muscle Myosins Isolated from Infants, Adults, and Patients with Hypertrophic Cardiomyopathy

Schier¹,

Adelstein²

1982

J. Clin. Invest.

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A B S T R A C T Human cardiac ventricular myosins were prepared from autopsy samples from nine adults, seven infants, and from surgical specimens from seven patients undergoing left ventricular septal myectomy for obstructive hypertrophic cardiomyopathy. Infant myosin differed from adult myosin in two important characteristics: (a) t-30% of the 27,000-dalton myosin light chain is replaced by a 28,000-dalton light chain, and (b) the actin-activated myosin MgATPase activity of infant myosin is significantly lower than that of adult myosin (64 nmol phosphate released/mg myosin per min vs. 124 nmol/mg per min at 37°C). The K+-EDTA ATPase activity of the myosin measured in 0.5M KC1 is also lower in infants (1,210 nmol/mg per min vs. 620 nmol/mg per min at 37°C), but the Ca++-activated ATPase is not significantly different. There were no differences in enzymatic activity between the normal adult and cardiomyopathic myosins.A detailed study was performed to investigate possible variations in the structure of the myosin heavy chain in infant, adult, and cardiomyopathic samples. There were no significant differences between infant and normal adult, or between normal adult and cardiomyopathic myosins seen in pyrophosphate polyacrylamide gel electrophoresis, or peptide mapping using alpha-chymotrypsin, papain, or cyanogen bromide to generate peptides.These results suggest that isoenzymes of human ventricular myosin do not exist for the myosin heavy chain in the specimens examined from infants, adults, and patients with obstructive hypertrophic cardiomyopaDr. Schier's present address is

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“…Other factors altered may include myocardial catecholamine sensitivity (37), turnover (38), or alteration of binding sites (39,40), availability of adenyl cyclase (41,42), functioning of the sodium (43), or calcium pump (44), effects on myosin adenosine (45), or a variety of other metabolic effects (46,47). These metabolic effects may also be related to the morphological abnormalities ob- served on electron microscopy.…”

Section: Discussionmentioning

confidence: 99%

“…This method ofproducing hypothyroidism has advantages to thyroidectomv in the dog because this species has abundant extrathyroidal, thyroid tissue, the presence of which frequently results in incomplete surgical removal of thyroid tissue (13). 45 d after 131I administration, thyroid function was determined using 1251_ thyroxine radioimmunoassay (Corning Glass Works, Science Products Div., Corning, N. Y.).…”

Section: Methods Animal Preparations Hypothyroidismii Was Induced In 20mentioning

confidence: 99%

Deleterious influence of hypothyroidism on evolving myocardial infarction in conscious dogs.

Karlsberg¹,

Friscia²,

Aronow³

et al. 1981

J. Clin. Invest.

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A B S T R A C T To study the influence of hypometabolism on evolving myocardial infarction in a model with intact autoregulation, we investigated 53 awake dogs after coronary artery occlusion. Severe hypothyroidism was induced by the intravenous administration of 1311. Animals were instrumented to obtain hemodynamic measurements, and regional myocardial blood flow was measured with radioactive microspheres. Infarct size was determined by the creatine kinase depletion method, and dysrhythmia analysis was performed from 24-h Holter monitor tapes in animals matched for infarct size. The microarchitecture of hypothyroid myocardium was determined by the electron microscope. Before coronary occlusion, mean systemic pressure in hypothyroid dogs was reduced by 14% and cardiac output reduced by 32%, with no change in left ventricular end-diastolic pressure, first derivative of left ventricular pressure rise, (dP/dt), or heart rate. After coronary occlusion, there was deterioration in hemodynamic measurements in both groups, with lower absolute levels of mean systemic blood pressure and cardiac output obtained in hypothyroid dogs. Hypothyroidism was detrimental to evolving infarction with a 36% increase in infarct size present in hypothyroid dogs (30±2%) compared to euthyroid controls (22±3%), P < 0.05. Dysrhythmias were more severe in hypothyroid dogs. There were no changes in the relationship between regional myocardial blood flow and the extent of infarction after coronary occlusion. Abnormalities in microarchitecture were present in hypothyroid dog myocardium. Severe hypometabolism in this model was associated with alterations in hemodynamics, more severe dysrhythmias and changes in microarchitecture. The combined effect of

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Stimulation of cardiac myosin adenosine triphosphatase in thyrotoxicosis.

Cited by 56 publications

References 52 publications

Role of thyroid hormone in postnatal circulatory and metabolic adjustments.

Role of thyroid hormone in postnatal circulatory and metabolic adjustments.

Structural and Enzymatic Comparison of Human Cardiac Muscle Myosins Isolated from Infants, Adults, and Patients with Hypertrophic Cardiomyopathy

Deleterious influence of hypothyroidism on evolving myocardial infarction in conscious dogs.

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