POSITIVE INOTROPIC AND LUSITROPIC EFFECTS OF TRIIODOTHYRONINE IN CONSCIOUS DOGS WITH PACING-INDUCED CARDIOMYOPATHY

Background: The effects of triiodothyronine (T-3) on systemic hemodyna mics, myocardial contractility (preload recruitable stroke work slope; M-w), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs. Methods: Dogs (n = 8) were chronica lly instrumented for measurement of aortic and LV pressure, dP/dt(max) , subendocardial segment length, and cardiac output. Dogs received esc alating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T-3 over 5 mi n at 1-H intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs mere then continuo usly paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporar ily discontinued after the development of severe LV dysfunction, and a dministration of T-3 was repeated. Results: T-3 produced immediate and sustained (24 h) increases (P < 0.05) in M-w and dP/dt(max) in dogs b efore the initiation of pacing, consistent with a positive inotropic e ffect. No changes in tau occurred. Rapid ventricular pacing over 3 wee ks increased baseline heart rate (sinus rhythm) and LV end-diastolic p ressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in M-w and dP/dt(max)) and diastolic (increase s in tau) dysfunction. T-3 caused immediate and sustained increases In M-w (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) arid decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after t he 20 mg/kg dose), indicating that this hormone enhanced myocardial co ntractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with n ormal LV function, T-3 did not affect heart rate and calculated indice s of myocardial oxygen consumption and reduced LV end-diastolic pressu re (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) i n cardiomyopathic dogs. Conclusions: The findings indicate that T-3 pr oduces favorable alterations in hemodynamics and modest positive inotr opic and lusitropic effects in conscious clogs with LV dysfunction pro duced by rapid LV pacing.