Systemic pretreatment with dimethyloxalylglycine increases myocardial HIF-1 alpha and VEGF production and improves functional recovery after acute ischemia/reperfusion

作者：Poynter Jeffrey A; Manulcyan Mariuxi C; Wang Yue; Brewster Benjamin D; Herrmann Jeremy L; Weil Brent R; Abarbanell Aaron M; Meldrum Daniel R^*

来源：Surgery, 2011, 150(2): 278-283.

DOI：10.1016/j.surg.2011.06.006

Background. Stem cells protect the heart from ischemic damage in part by the release of cytoprotective growth factors, particularly vascular endothelial growth factor (VEGF). Production of VEGF is regulated in part by levels of the transcription factor hypoxia inducible factor 1-alpha (HIF-1 alpha). Dimethyloxalylglycine (DMOG) prevents the deactivation of HIF-1 alpha and increases VEGF production. However, the effects of systemic DMOG treatment on myocardial tolerance for ischemia are unknown. We hypothesized that systemic pretreatment with DMOG would improve myocardial ischemic tolerance.
Methods. To study this hypothesis, adult male rats were randomly given an intraperitoneal injection of DMOG (40 mg/kg in 1 mL saline, n = 5) or saline (1 mL, n = 6) 24 h before cardiectomy and isolated heart perfusion. All hearts were subjected to 15 min equilibration, 25 min ischemia and 40 min reperfusion. Myocardial function was continuously monitored. Following reperfusion, myocardial homogenates were analyzed for HIF-1 alpha and VEGF production.
Results. We observed that hearts in the DMOG group exhibited greater recovery of left ventricular developed pressure LVDP, +dP/dt and -dP/dt. Myocardial HIF-1 alpha and VEGF levels were increased by DMOG therapy.
Conclusion. In conclusion, systemic pretreatment with DMOG augments post-ischemic myocardial functional recovery through increased HIF-1 alpha levels and greater VEGF production. (Surgery 2011;150:278-83.)

• 出版日期2011-8