The myocardial contractile response to physiological stress improves with high saturated fat feeding in heart failure.
Impaired myocardial contractile function is a hallmark of heart failure (HF), which may present under resting conditions and/or during physiological stress. Previous studies have reported that high fat feeding in mild to moderate HF/left ventricular (LV) dysfunction is associated with improved contractile function at baseline. The goal of this study was to determine whether myocardial function is compromised in response to physiological stress and to evaluate the global gene expression profile of rats fed high dietary fat after infarction. Male Wistar rats underwent ligation or sham surgery and were fed normal chow (NC; 10% kcal fat; Sham + NC and HF + NC groups) or high-fat chow (SAT; 60% kcal saturated fat; Sham + SAT and HF + SAT groups) for 8 wk. Myocardial contractile function was assessed using a Millar pressure-volume conductance catheter at baseline and during inferior vena caval occlusions and dobutamine stress. Steady-state indexes of systolic function, LV +dP/dt(max), stroke work, and maximal power were increased in the HF + SAT group versus the HF + NC group and reduced in the HF + NC group versus the Sham + NC group. Preload recruitable measures of contractility were decreased in HF + NC group but not in the HF + SAT group. beta-Adrenergic responsiveness [change in LV +dP/dt(max) and change in cardiac output with dobutamine (0-10 microg x kg(-1) x min(-1))] was reduced in HF, but high fat feeding did not further impact the contractile reserve in HF. The contractile reserve was reduced by the high-fat diet in the Sham + SAT group. Microarray gene expression analysis revealed that the majority of significantly altered pathways identified contained multiple gene targets correspond to cell signaling pathways and energy metabolism. These findings suggest that high saturated fat improves myocardial function at rest and during physiological stress in infarcted hearts but may negatively impact the contractile reserve under nonpathological conditions. Furthermore, high fat feeding-induced alterations in gene expression related to energy metabolism and specific signaling pathways revealed promising targets through which high saturated fat potentially mediates cardioprotection in mild to moderate HF/LV dysfunction.
Dept. of Physiology and Biophysics, School of Medicine E521, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106-4970, USA.
Jessica M
JM
Berthiaume
Molly S
MS
Bray
Tracy A
TA
McElfresh
Xiaoqin
X
Chen
Salman
S
Azam
Martin E
ME
Young
Brian D
BD
Hoit
Margaret P
MP
Chandler
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output; D004041:Dietary Fats / Q000008:administration & dosage* / Q000097:blood; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D004734:Energy Metabolism; D005227:Fatty Acids / Q000008:administration & dosage* / Q000097:blood; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015398:Signal Transduction; D013312:Stress, Physiological; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics; D017725:Ventricular Pressure
D000318:Adrenergic beta-Agonists; D004041:Dietary Fats; D005227:Fatty Acids; D004280:Dobutamine