The Sinus Node Inhibitor UL-FS 49 Lacks Significant Inotropic Effect

UL-FS 49 is a sinus node inhibitor that has been reported to reduce heart rate and may be useful in improving myocardial oxygen supply vs. demand. However, previous studies performed in a variety of preparations have produced mixed results regarding the independent inotropic effect of UL-FS 49. To determine whether UL-FS 49 has an inotropic effect, we measured both steady-state hemodynamic responses and transient hemodynamic responses to random preload and afterload changes, both with and without UL-FS 49. We found that under steady-state conditions, the effect of UL-FS 49 is so small that it would be of doubtful physiologic significance: a 3% increase in stroke volume (p = 0.007) and 7% increase in peak positive dP/dt (p = 0.051), in the presence of no statistically significant differences in end-diastolic pressure, end-diastolic volume, peak systolic pressure, end-systolic pressure, or heart rate. The more powerful multiple linear regression modeling of hemodynamic transient sequences resulting from random preload and afterload changes showed that UL-FS 49 is without a statistically significant direct effect on left ventricular function. We conclude that UL-FS 49 has no physiologically important direct effect on left ventricular pump function.