The role of calcium handling in the improved contractile function associated with high‐fat feeding in heart failure

Abstract

Heart failure (HF) is characterized by deteriorating left ventricular (LV) function. High saturated fat diets (SAT) are associated with increased risks for lipotoxicity & contractile dysfunction. However, HF animals fed SAT exhibit improved in vivo LV contractility versus HF animals fed normal chow (NC) as assessed by LV +dP/dt max. Ca2+ handling properties are known to be altered & contribute to HF. Therefore, we hypothesize that LV contractile dysfunction associated with alterations in Ca2+ handling properties in HF are improved with SAT. Male rats underwent coronary ligation or sham surgery (SH) & fed NC or SAT for 8 weeks. Cardiomyocytes were isolated, followed by measurements of cell shortening, Ca2+ transients, sarcoplasmic reticulum (SR) Ca2+ content, & L‐type Ca2+ current. Myocytes from both HF groups were hypertrophied & their Ca2+ decay (τ1/2) prolonged versus SH. HF+NC myocytes exhibited decreased cell shortening at 1Hz but increased Ca2+ transients despite decreased SR Ca2+ content versus SH+NC. HF+NC myocytes had depressed L‐type Ca2+ currents & a diminished response to β‐adrenergic stimulation versus SH+NC which may contribute to the decrease in cell shortening. However, cell shortening, L‐type ca2+ currents at baseline and in response to β‐adrenergic stimulation were not decreased in HF animals fed high fat and thus, may account for in vivo differences in contractility. (Grant: NHLBI HL‐081857)