Schaefer S, Ramasamy R
Division of Cardiovascular Medicine, University of California, Davis 95616, USA.
Cardiovasc Res. 1997 Jul;35(1):90-8. doi: 10.1016/s0008-6363(97)00087-4.
Fasting increases myocardial glycogen content and has been shown to limit injury and improve recovery following no-flow ischaemia in the isolated heart. However, the protective role of glycogen loading per se in fed animals has been questioned by data in preconditioned animals showing that reduced glycogenolysis may be protective prior to no-flow ischemia. Therefore, we hypothesized that fasting protects the globally ischemic heart by mechanisms separate from glycogen loading.
Isolated hearts from rats fasted for 24 h were retrogradely perfused using glucose substrate and subjected to 20 min of global no-flow ischemia. Fed rats were identically perfused either under control conditions (glucose substrate) or with an intervention chosen to increase tissue glycogen (glucose plus insulin, [insulin]) prior to ischemia. Functional recovery and creatine kinase (CK) release were measured during reperfusion. Nuclear magnetic resonance spectroscopy was used to measure intracellular pH, phosphorylated glycolytic intermediates and high-energy phosphates, while the lactate and pyruvate contents of the hearts were measured prior to and at the end of ischemia.
Heart from fasted animals had significantly increased glycogen content prior to ischemia (76.6 +/- 2 vs. 40.9 +/- 3 mumol glu/gdw in control hearts, P < 0.05) as did hearts exposed to insulin (88.6 +/- 10 mumol glu/gdw), but only hearts from fasted animals had greater glycogen utilization during ischemia. Hearts from fasted animals also had lower levels of lactate relative to pyruvate (L/P) under baseline conditions and, on reperfusion, reduced CK release (fasted: 183 +/- 48 versus control: 756 +/- 56 IU/gdw, P < 0.05). Conversely, insulin hearts had increased CK release (1831 +/- 190 IU/gdw, P < 0.001 vs control) and worse functional and metabolic recovery on reperfusion. Compared to the insulin hearts, hearts from fasted animals had both less acidosis and less rapid depletion of ATP during ischemia, as well as lower accumulation of glycolytic intermediates.
Fasting protects the heart from ischemic injury and is associated with a lower L/P ratio and increased glycogen utilization during ischemia. In contrast, increasing glycogen content in hearts from fed animals using insulin limits glycogen utilization, increases ischemic injury, and impairs both functional and metabolic recovery under conditions of 20 min of global no-flow ischemia.
禁食可增加心肌糖原含量，并且已证明在离体心脏无复流缺血后，禁食能限制损伤并促进恢复。然而，预适应动物的数据对进食动物中糖原负荷本身的保护作用提出了质疑，这些数据表明，减少糖原分解在无复流缺血前可能具有保护作用。因此，我们推测禁食通过与糖原负荷无关的机制保护全心缺血的心脏。
将禁食24小时的大鼠的离体心脏用葡萄糖底物进行逆行灌注，并进行20分钟的全心无复流缺血。对进食大鼠在对照条件下（葡萄糖底物）或在缺血前用选择的干预措施增加组织糖原（葡萄糖加胰岛素，[胰岛素]）进行相同的灌注。在再灌注期间测量功能恢复和肌酸激酶（CK）释放。使用核磁共振波谱法测量细胞内pH、磷酸化糖酵解中间产物和高能磷酸盐，同时在缺血前和缺血结束时测量心脏的乳酸和丙酮酸含量。
禁食动物的心脏在缺血前糖原含量显著增加（对照心脏中为76.6±2 vs. 40.9±3 μmol葡萄糖/g干重，P<0.05），暴露于胰岛素的心脏也是如此（88.6±10 μmol葡萄糖/g干重） , 但只有禁食动物的心脏在缺血期间糖原利用率更高。禁食动物的心脏在基线条件下相对于丙酮酸（L/P）的乳酸水平也较低，并且在再灌注时，CK释放减少（禁食组：183±48 vs. 对照组：756±56 IU/g干重，P<0.05）。相反，胰岛素处理的心脏CK释放增加（1831±190 IU/g干重，与对照组相比P<0.001），并且在再灌注时功能和代谢恢复较差。与胰岛素处理的心脏相比，禁食动物的心脏在缺血期间酸中毒较轻，ATP消耗较慢，糖酵解中间产物积累也较少。
禁食可保护心脏免受缺血损伤，并且与较低的L/P比值和缺血期间增加的糖原利用率相关。相比之下，使用胰岛素增加进食动物心脏中的糖原含量会限制糖原利用，增加缺血损伤，并在20分钟全心无复流缺血条件下损害功能和代谢恢复。
