triiodothyronine--reverse and Heart-Arrest

Serum thyroxine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were followed for 24 h in dogs resuscitated following 9 min of controlled cardiac arrest (CA). Total T4, free T4, total T3, and free T3 decreased, while reverse T3 was elevated in the 24 h following resuscitation. Similar changes occurred with only 30 sec of CA. Levothyroxine sodium (L-T4) post-CA (7.5 micrograms/kg/h = CA + 7.5 or 15 micrograms/kg/h = CA + 15) increased total T4, free T4, and total T3. Free T3 decreased in the CA + 7.5 group but did not fall in CA + 15 group. Neurologic function improved significantly by 6 through 24 h (p < 0.05). Follow-up studies infusing T3 or rT3 failed to improve neurologic outcome. Systemic oxygen consumption (VO2) and delivery was assessed in a separate group of seven dogs that received a pre-CA L-T4 infusion of 15 micrograms/kg/h for 1.5 h and L-T4 infusion for 6 h afterward while controls (n = 7) received saline. Systemic VO2, VCO2, and RQ were calculated from blood contents and cardiac output and serum levels of circulating TSH, T4, FT4, T3, FT3, and rT3 were measured before L-T4 and periodically over 6 h. L-T4 maintained significantly higher T4, FT4, T3, FT3, rT3, VO2, and cardiac output compared to controls. No change in canine TSH was detected. Rapid and dramatic decreases in thyroid hormones following resuscitation indicate a significant acute serum hypothyroid state that may benefit from L-T4 treatment. L-T4 enhances systemic oxygen consumption and delivery and these changes may contribute to L-T4's neural protective effect.

Topics: Animals; Carbon Dioxide; Cardiac Output; Cardiopulmonary Resuscitation; Dogs; Heart Arrest; Hypothyroidism; Male; Oxygen Consumption; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Documentation of profound changes in serum thyroid hormone concentrations associated with cardiac arrest and resuscitation, as well as other acute emergencies, have spurred evaluation of possible therapeutic thyroid hormone administration. Acute and significant, this state, characterized by abnormally low serum thyroid hormone concentrations, may indicate selective thyroid replacement therapy. In a previous investigation, post-resuscitation infusion of levothyroxine sodium (L-T4) to normalize serum 3,5,3'-triiodothyronine (T3) concentrations was associated with significant reduction of neurologic deficit caused by severe global cerebral ischemia. Since L-T4 has been reported to act directly or via one of its metabolites, most likely T3, this most active form of thyroid hormone was tested. When L-T4 reduced the neurologic deficit, an increase in 3,3',5'-triiodothyronine (rT3) was also observed. This study therefore determined whether a post-resuscitation treatment with either T3 (n = 8) or rT3 (n = 8) provided protection against global cerebral ischemia comparable to that of L-T4. Global cerebral ischemia was achieved with 9 min of ventricular fibrillation. Following resuscitation, one of three solutions (saline group as a control) was infused for 24 h at rates that reproduced the normal serum T3 concentrations or the rT3 concentrations achieved previously during the L-T4 therapy. The successful elevation of T3 and mimicking rT3 concentrations was assessed and confirmed by radioimmunoassay (RIA). In addition, TSH levels were measured by a novel RIA specific for canine thyroid-stimulating hormone (cTSH). Neurologic deficit was assessed with a well-standardized neurologic deficit examination. In contrast to previous studies using L-T4 infusion, no significant reduction of neurologic deficit was observed. Serum thyroid hormone changes confirmed previously described decreases and in no case did changes in cTSH appear causal in these changes. Thus, we concluded that L-T4 may offer a therapeutic advantage over T3 or rT3.

Topics: Animals; Brain Ischemia; Dogs; Heart Arrest; Male; Neurologic Examination; Radioimmunoassay; Resuscitation; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Previous studies have shown abnormal thyroid hormone profiles during cardiac arrest. We explored this association further by characterizing plasma thyroid hormone profiles in 473 patients with out-of-hospital cardiac arrest and correlating them with clinical outcomes. Paramedics collected blood at the end of attempted resuscitation regardless of success. Bloods were collected and processed in a similar manner from 18 control subjects randomly selected from the community. Total thyroxine and total triiodothyronine were lower and reverse triiodothyronine and thyrotropin were higher in cardiac arrest patients than control subjects (all p < 0.001). Except for reverse triiodothyronine, findings were similar for a subgroup of cardiac arrest patients considered to be previously healthy (n = 30). Being discharged alive was associated with total thyroxine, total triiodothyronine and reverse triiodothyronine concentrations closer to the control range and thyrotropin concentrations farther from it, namely higher. In a multivariate stepwise model, only total triiodothyronine and thyrotropin were significantly associated with outcome. Whether these profoundly abnormal profiles represent a pre-existing state or a sudden change of thyroid hormone concentrations cannot be answered with this retrospective study. These observations suggest that thyroid hormones may play a role in the etiology of cardiac arrest, its prognosis, or both.

Topics: Aged; Female; Heart Arrest; Humans; Male; Middle Aged; Retrospective Studies; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Thyroid function was evaluated in cardiac arrest (CA), a condition associated with marked activation of the pituitary-adrenal axis. Blood samples were obtained in 24 patients immediately after diagnosis of CA and again ten minutes later. Samples were also obtained from 22 patients admitted consecutively to the intensive care unit (ICU). Abnormalities of thyroid indexes among patients on the ICU who had not experienced CA were low triiodothyronine (T3) in 45%, low thyroxine (T4) in 32%, low free T4 (equilibrium dialysis) in 21%, and elevated reverse T3 levels in 36%. The alterations of thyroid values were both more common and marked in patients with CA, with abnormally low T3 in 84% of the patients, low T4 in 65%, low free T4 in 65%, and high reverse T3 in 80%. Thyroxine-binding globulin and prealbumin concentrations were below the normal range in 40% and 21% of patients with CA. A thyroid hormone-binding inhibitor was detected in 38% of patients with CA. Thyroglobulin level was slightly high in patients with CA but not significantly different from controls on the ICU. The abnormalities present at zero minutes were further exaggerated ten minutes after CA. We conclude that abnormalities on tests measuring thyroid function are extremely common during the cardiovascular emergency of CA.

Topics: Adult; Aged; Aged, 80 and over; Female; Heart Arrest; Humans; Male; Middle Aged; Thyroglobulin; Thyroid Gland; Thyroxine; Thyroxine-Binding Proteins; Time Factors; Triiodothyronine; Triiodothyronine, Reverse