The effect of triiodothyronine on myocardial contractile performance after epinephrine exposure: implications for donor heart management.
BACKGROUND
This study analyzes in the experimental model of isolated human atrial myocardium whether the myocardial contractile depression occurring after high-dose/long-term catecholamine exposure (as typically occurring in brain-dead organ donors) can be reversed by thyroid hormone administration.


METHODS
Isolated trabeculae were prepared from atrial myocardium from patients undergoing coronary artery bypass (n = 15). Initial measurements of isometric force were carried out (measurement conditions of 37 degrees C, Krebs Henseleit solution, supramaximal electrical stimulation, 1 Hz, at optimal length). Then the trabeculae were incubated for 6 hours at 26 degrees C in a Krebs Henseleit solution containing epinephrine 10(-7) mol/L and the fluorescent dye FURA-2/AM for calcium measurements. At the end of the incubation period, isometric force, isotonic shortening, and intracellular calcium transient (FURA-2 "ratio method") were measured. After 30 minutes administration of triiodothyronine (5 x 10(-9) mol/L), the measurements were repeated. Control groups included 6 hours incubation in 4 degrees C Krebs Henseleit solution (n = 5); 6 hours incubation in 26 degrees C FURA-2/AM (n = 5); and 6 hours incubation in epinephrine 10(-7) mol/L (n = 5).


RESULTS
After 6 hours catecholamine exposure isometric force declined significantly to 56.8% (p < .0001) and isotonic shortening to 54% of its initial value (p < .01). Administration of triiodothyronine was associated with a significant recovery of the isotonic shortening amplitude (p < .005), of isometric force development (p < .01), an increased velocity of force development (p < .0001), and of diastolic force decay (p < .005). At the same time the shape of the intracellular calcium transient became smaller as a result of an accelerated diastolic decay. The amplitude of the calcium transient remained unaltered, whereas the calcium time integral was reduced (p < .05).


CONCLUSIONS
In the model of isolated human myocardium, experimental depression of the contractile performance resulting from long-term catecholamine exposure could be reversed by a 30-minute triiodothyronine incubation. The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine. The data provide additional knowledge to explain the successful administration of triiodothyronine in donor heart management.
Timek
T
T
Department of Cardiac Surgery, University of Heidelberg, Germany.
Bonz
A
A
Dillmann
R
R
Vahl
C F
CF
Hagl
S
S
D002118:Calcium / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D016027:Heart Transplantation; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D002118:Calcium; D004837:Epinephrine