Does the presence of high levels of fatty acids (palmitate) during or after ischemia affect the functional recovery of isolated hearts from diabetic and control rats?
High levels of fatty acids impair functional recovery of ischemic hearts differently in diabetic versus control rats, depending on whether exposure occurs during ischemia or reperfusion.
In this study we determined the effects of high levels of fatty acids on recovery of heart function when present either during or after ischemia. Isolated working hearts from 6-wk streptozotocin diabetic and control rats perfused with 11 mM glucose were subjected to 25 min of global ischemia followed by 30 min of aerobic reperfusion. Four groups were studied: 1) 1.2 mM palmitate present before, during, and after ischemia; 2) 1.2 mM palmitate present before and during ischemia, followed by reperfusion in the absence of palmitate; 3) no palmitate before and during ischemia, followed by 1.2 mM palmitate during reperfusion; and 4) no palmitate before and during ischemia or during reperfusion. In control hearts, palmitate during reperfusion depressed recovery of function regardless of whether palmitate was present or absent during ischemia. In contrast, palmitate present during reperfusion did not depress recovery of mechanical function in the diabetic rat hearts. However, the presence of palmitate during ischemia itself in diabetic rat hearts was detrimental to recovery of mechanical function. The presence of palmitate during ischemia resulted in an accelerated rate of ATP loss and a decreased rate of lactate accumulation during ischemia, although this effect was similar in control and diabetic rat hearts. Our results demonstrate that high concentrations of fatty acids depress functional recovery of control rat hearts during the reperfusion period but depress recovery of function in diabetic rat hearts when present during ischemia itself.
Lopaschuk et al. (Tue,) studied this question.