Positive inotropic and lusitropic effects of triiodothyronine in conscious dogs with pacing-induced cardiomyopathy

Background: The effects of triiodothyronine (T-3) on systemic hemodynamics, 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 chronically instrumented for measurement of aortic and LV pressure, dP/dt(max), subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T-3 over 5 min 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 continuously paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration 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 before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in M-w and dP/dt(max)) and diastolic (increases 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) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T-3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs. Conclusions: The findings indicate that T-3 produces favorable alterations in hemodynamics and modest positive inotropic and lusitropic effects in conscious clogs with LV dysfunction produced by rapid LV pacing.