Department of Cardiovascular Surgery, Methodist Hospital, Indiana University School of Medicine, Indianapolis, IN, USA.
Surgery. 2011 Aug;150(2):191-6. doi: 10.1016/j.surg.2011.05.009.
Cytoprotective growth factors such as vascular endothelial growth factor (VEGF) play important roles in myocardial protection from ischemia/reperfusion (I/R). Accumulating evidence suggests that the hypoxia-inducible factor 1 (HIF-1) pathway is a key regulator of VEGF production in the setting of I/R. The prolyl hydroxylase inhibitor mimosine can increase VEGF production through the HIF-1 pathway. We hypothesized that infusion of preischemic intracoronary mimosine would improve myocardial functional recovery after I/R.
Isolated male rat hearts were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Immediately prior to ischemia, ischemic hearts received intracoronary infusions of vehicle or solutions of 0.3, 3, or 30 μM mimosine. Myocardial function was recorded throughout the experiments. Functional data were analyzed with two-way analysis of variance adjusted with the Bonferroni correction.
Preischemic myocardial function was equivalent. All hearts had significant reductions in function at the beginning of reperfusion. Hearts treated with 0.3 or 3 μM mimosine infusions exhibited greater recovery of left ventricular developed pressure compared to vehicle. The maximal positive value of the first derivative of pressure (+dP/dt) was greater in hearts treated with 0.3 μM mimosine compared to hearts treated with vehicle. No differences were observed in recovery of end-diastolic pressure or the maximal negative value of the first derivative of pressure (-dP/dt).
Preischemic intracoronary mimosine infusion improves myocardial functional recovery after I/R.
细胞保护生长因子，如血管内皮生长因子（VEGF），在心肌缺血/再灌注（I/R）损伤中发挥重要的保护作用。越来越多的证据表明，缺氧诱导因子 1（HIF-1）通路是 I/R 条件下 VEGF 产生的关键调节因子。脯氨酰羟化酶抑制剂米莫司汀可以通过 HIF-1 通路增加 VEGF 的产生。我们假设，在缺血前经冠状动脉内输注米莫司汀可以改善 I/R 后的心肌功能恢复。
分离雄性大鼠心脏，进行 15 分钟的平衡，25 分钟的缺血，和 40 分钟的再灌注。在缺血前，缺血心脏接受冠状动脉内输注载体或 0.3、3 或 30 μM 米莫司汀溶液。在整个实验过程中记录心肌功能。使用双因素方差分析对功能数据进行分析，并使用 Bonferroni 校正进行调整。
缺血前的心肌功能相当。所有心脏在再灌注开始时功能均显著降低。与载体相比，接受 0.3 或 3 μM 米莫司汀输注的心脏左心室发展压的恢复更大。与接受载体的心脏相比，接受 0.3 μM 米莫司汀处理的心脏的压力第一导数的最大正值（+dP/dt）更大。舒张末期压力或压力第一导数的最大负值（-dP/dt）的恢复没有差异。
缺血前经冠状动脉内输注米莫司汀可改善 I/R 后的心肌功能恢复。
