Triiodothyronine reverses depressed contractile performance after excessive catecholamine stimulation

Background. Conflicting results have been reported regarding the acute effe cts of triiodothyronine (T-3) on myocardial contractile performance. The pr esent study analyzes the role of T-3 in reversing the depressant effect of excessive catecholamine stimulation in isolated porcine left ventricular my ocardium. Methods. Thirty-six left ventricular trabeculae (0.4 x 6.0 mm) obtained fro m 6 pigs were used for measurements of isometric force development, isotoni c shortening, and intracellular calcium in three experimental series (measu rement conditions: 37 degrees C; optimal length; supramaximal electrical st imulation, 1 Hz; calcium measurement, fura-2 ratio method; frequency, 225 H z). In series 1, isometric force development was measured before and after a 60-minute incubation with 10(-7) mol/L epinephrine in preparations with ( n = 6) and without (n = 6) preceding fura-2 loading for calcium measurement s. In series 2, the acute effects of a 30-minute administration of T-3 (10( -9) mol/L) on isometric force and intracellular calcium were analyzed (n = 6). In series 3, after simultaneous fura-2 loading and a 6-hour 10(-7) mol/ L epinephrine exposure the effects of T-3 (10(-9) mol/L, 30 minutes) on for ce development, shortening, and intracellular calcium transient were analyz ed. Results. Long-term and high-dose epinephrine exposure induced a severe cont ractile depression with a significant reduction of isometric force developm ent (p < 0.05) and increased diastolic (p < 0.001) and systolic calcium (p < 0.001). In normal porcine myocardium T-3 had no effect on the extent of i sometric force generation but accelerated the time course of force developm ent (p < 0.05) and increased the calcium transient (p < 0.001). After induc tion of myocardial depression by epinephrine exposure T-3 accelerated the i ntracellular calcium transients and reduced diastolic calcium. Triiodothyro nine increased the shortening amplitude and the force amplitude (p < 0.01). Conclusions. Triiodothyronine reverses depressed contractile performance af ter preceding high-dose epinephrine exposure in isolated porcine myocardium . Increased force amplitudes and unaltered or even reduced intracellular ca lcium transients argue in favor of a resensitization of the contractile app aratus for calcium by T-3. The study supports a potential role for T-3 trea tment in depressed myocardium after previous excessive catecholamine exposu re leg, brain death, catecholamine treatment, ischemia). (C) 1998 by The So ciety of Thoracic Surgeons.