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.
Chen
Z Y
ZY
Department of Medicine, University of Vermont, Burlington.
Slinker
B K
BK
D000465:Algorithms; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects
D001552:Benzazepines; D002317:Cardiovascular Agents; C043636:zatebradine