Reduction of cardiac functional reserve and elevation of aortic stiffness in hyperlipidemic Yucatan minipigs with systemic and coronary atherosclerosis.
To test the hypothesis that cardiac functional reserve is reduced in animals with severe atherosclerosis, Yucatan minipigs were fed a high-cholesterol diet (Chol) for 8 months. Half of them was made diabetic, an additional risk factor for atherosclerosis, with streptozotocin (STZ). Another group of age-matched minipigs were fed a normal diet as controls. At the end of the treatment period, animals were instrumented for the measurement of cardiovascular hemodynamic parameters under isoflurane anesthesia. Cardiac functional reserve was measured by the magnitude of the inotropic response to isoproterenol stress. Hyperlipidemic minipigs developed severe atherosclerotic plaques in the aorta, coronary and iliac artery, accompanied by an increase in the aortic stiffness indexed by increases in pulse wave velocity and augmentation index. These vascular changes were more severe in STZ-induced insulin-dependent diabetes mellitus. The isoproterenol-induced increase in left ventricular contractility (dP/dt) and relaxation (-dP/dt) and, consequently, cardiac output were also significantly reduced in both the Chol groups with or without STZ, compared to control group. Thus, cardiac functional reserve measured by isoproterenol-stimulated responses was reduced in atherosclerotic minipigs, which was further diminished in diabetes.
Wang
Yi-Xin
YX
Department of Pharmacology, Berlex Bioscience, P.O. Box 4099, 600 Hilltop Blvd., Richmond, CA 94804-0099, USA. jim_wang@berlex.com
Fitch
Rick
R
Li
Weiwei
W
Werner
Matthias
M
Halks-Miller
Meredith
M
Lillis
Bill
B
Vergona
Ronald
R
Post
Joe
J
Sullivan
Mark E
ME
Verhallen
Peter F
PF
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006949:Hyperlipidemias / Q000473:pathology / Q000503:physiopathology*; D007083:Iliac Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D013556:Swine, Miniature
D004041:Dietary Fats; D007545:Isoproterenol