Ann Thorac Surg 1995;60:299
© 1995 The Society of Thoracic Surgeons
Discussion
Discussion
See also page 292.
DR GIDEON MERIN (Jerusalem, Israel): We also were intrigued by the effect of T3 on myocardial performance in the setting of isolated heart preparation of Langendorff and could establish that it probably works through mediation by calcium channels. This beneficial effect could be abolished completely by the addition of verapamil into the solution.
DR TIMOTHY S. HALL (New Brunswick, NJ): You emphasized a preemptive treatment. Do you have any data on posttreatment alone? Indicate your dosing scheme.
DR WALKER : The initial studies we performed were in control and cardiomyopathic myocytes, where we added thyroid hormone and measured the acute effects. We have not done studies where thyroid hormone is added at the termination of exposure to cardioplegic arrest to determine whether a similar effect occurs as is seen with pretreatment. As far as the dose that we used in the myocytes, it is a pharmacologic dose based on dose--response studies done at the initiation of the study. The dose that we used, 80 pmol/L, is the ED100, or the maximal effective dose. We are embarking on an in vivo study at this time where we intend to use a dose of approximately 0.6 µg/kg body weightAu: OK? in our animals to study this same effect in vivo.
DR DAVIS C. DRINKWATER, JR (Los Angeles, CA): Doctor Walker, the work in the transplant sphere would indicate that with brain death, a hypophyseal problem and a myocardial dysfunction may respond to thyroid therapy. In terms of your study it is obviously a more direct mode of action. Would you discuss a possible mechanism in addition to a receptor phenomenon?
DR WALKER: Currently, we are investigating the mechanisms of acute action of thyroid hormone. The effects of thyroid hormone are classically thought of as chronic effects that occur after administration over a longer period of time, at least 18 to 24 hours. The effects that we see occur within the first few minutes of exposure. It has been shown by other investigators that thyroid hormone may act acutely through alterations in the transport of amino acids, glucose, or small ions; that it may augment sodium channel bursting; or that it may acutely interact with the ß-adrenergic receptor. Therefore, we are looking at several potential mechanisms and have some preliminary results that are very promising. Specifically with thyroid hormone and administration of a concomitant ß-adrenergic agonist we have observed an increase in L-type Ca+2 channel current density, an increase in intracellular ionized Ca+2 as measured by FURA-2, and an increase in the production of cyclic AMP. Currently, we are looking at Na+, K+-ATPase hydrolytic activity. These projects will allow us to further elucidate the acute mechanisms of action of T3.
Related Article
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3,5,3'Triiodo-L-Thyronine Pretreatment With Cardioplegic Arrest and Chronic Left Ventricular Dysfunction
- Jennifer D. Walker, Fred A. Crawford, Jr, and Francis G. Spinale
Ann. Thorac. Surg. 1995 60: 292-299.
[Abstract]
[Full Text]
