Reduced cardiac functional reserve in apolipoprotein E knockout mice.
Several years ago, the authors reported that aortic flow velocity under resting conditions was significantly higher in apolipoprotein E knockout (apoE-KO) mice than in age-matched C57Black/6J wildtype (WT) controls. The goal of this study was to examine whether the cardiac functional reserve is impacted in response to a pharmacological stress agent in apoE-KO mice. Cardiac function was measured noninvasively by the Doppler ultrasound method at baseline and at 1 min, 5 min, 10 min, and 20 min after intraperitoneal injection of dobutamine at the doses of 1 microg/g, 3 microg/g, or 10 microg/g in 16-month-old male apoE-KO (n = 9) and WT (n = 10) mice under light anesthesia with 1.5% isoflurane via inhalation. The baseline peak and mean aortic flow velocities were 39% to 48% higher, and left ventricular contractility measured by peak acceleration rate of aortic flow velocity was 24% higher in apoE-KO compared with WT mice (P < 0.01). Dobutamine stress dose-dependently increased cardiac function, which, however, was significantly smaller with a right shift of the dose-response curve in apoE-KO mice compared with WT controls. The hypotensive response to dobutamine was not significantly different between the 2 groups. Thus, despite an elevated resting aortic flow velocity and left ventricular contractility, cardiac functional reserve in response to dobutamine stress was significantly reduced in apoE-KO mice, which could be the consequence of coronary atherosclerosis and endothelial dysfunction that limits blood supply to the heart.
Vincelette
Jon
J
Department of Pharmacology, Berlex Biosciences, Richmond, California.
Martin-McNulty
Baby
B
Vergona
Ronald
R
Sullivan
Mark E
ME
Wang
Yi-Xin
YX
D000818:Animals; D001011:Aorta / Q000502:physiology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D001783:Blood Flow Velocity; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013566:Sympathomimetics / Q000494:pharmacology
D001057:Apolipoproteins E; D013566:Sympathomimetics; D004280:Dobutamine