Fasting limits the increase in intracellular calcium during ischemia in isolated rat hearts

Introduction: Fasting has been shown to limit ischemic injury and improve functional activity after global ischemia. Because calcium overload is considered a mechanism of ischemic injury, we hypothesized that fasting would limit the accumulation of intracellular calcium [Ca]_i during ischemia, potentially due to reduced accumulation of intracellular sodium [Na]_i. Methods: To address this hypothesis, hearts isolated from rats fed either a normal diet or fasted for 24 hours underwent 20 min of global ischemia at 37°. In addition to functional parameters, [Na]_i and [Ca]_i were measured using ²³Na and ¹⁹F spectroscopy using thulium-DOTP^-5 and 5F-BAPTA, respectively. In vitro measurement of sarcoplasmic reticulum calcium uptake and release, as well as activity of the sarcolemmal Na-Ca exchanger, was performed in hearts from fed and fasted animals under baseline and ischemic conditions. Results: Hearts from fasted animals showed greater recovery of developed pressure (37 ± 9 vs. 11 ± 6 cm H₂O, p < 0.05) and less contracture (end-diastolic pressure 25 ± 2 vs. 47 ± 2 cm H₂O, p < 0.05) by the end of the reperfusion period. [Na]_i was similar in the 2 groups during the first half of the ischemic period, albeit with a higher concentration of [Na]_i in hearts from fed compared to fasted animals at reperfusion. Fasting markedly limited calcium accumulation during ischaemia, with end-ischemic calcium being 419 ± 46 nM in the hearts from fasted animals and 858 ± 140 nM in the hearts from fed animals (p < 0.01). There was no significant effect of fasting on calcium uptake or release by the SR, nor on sarcolemmal Na-Ca exchange activity. Conclusions: Fasting for 24 hours improves functional recovery and markedly limits [Ca]_i accumulation during ischemia and early reperfusion. The mechanism for this phenomenon remains to be elucidated.