90th Annual Meeting Abstracts
The Effects of Chronic Myocardial Ischemia on Adjacent Normal Myocardial Microvasculature
*Michael P Robich, MD1, *Robert M Osipov, MD1, *Jun Feng, MD1, *Yuhong Liu, MD1, *Richard T Clements, PhD1, *Cesario Bianchi, MD, PhD1, Frank W Sellke, MD2
1Beth Israel Deaconess Medical Center, Boston, MA;2Warren Alpert School of Medicine, Brown University, Providence, RI
Objective: Angiogenesis, native and therapeutic, is one method of restoring perfusion to ischemic myocardium. It is unknown how normally perfused myocardium near an ischemic territory responds to the nearby insult. We utilized a swine model of chronic myocardial ischemia to determine how normal myocardium adjacent to an ischemic area may contribute to angiogenesis over time.
Design: Non-randomized animal study
Setting: Basic science laboratory, academic medical center
Intervention: Yorkshire mini-swine (n=8) were subjected to chronic myocardial ischemia by placing an ameroid constrictor on the proximal left circumflex coronary artery. Swine sacrifice was conducted four and seven weeks after ameroid placement.
Main Outcome Measures: Microvessel reactivity, oxidative stress, immunoassays
Results: Microvessels subjected to vasoconstrictors endothelin 1 and serotonin demonstrated smaller contraction responses at 7 weeks when compared to 4 weeks (58±2.4% at 4 weeks vs. 30.2±9.8% at 7 weeks, p=0.038 and 50.2±10.6% at 4 weeks vs. 18.5±5.1% at 7 weeks, p<0.001, respectively). Protein expression at 7 weeks demonstrated significant upregulation of apoptosis inducing factor, AIF, (1.83 fold, p=0.018), HSP90 (2.35 fold, p=0.012), and phospho-Erk 1/2(Thr185/Tyr187)(2.53 fold, p =0.0013). There was no difference in expression of VEGF (p=0.24), FGF2 (p=0.19), Dll4 (p=0.89), eNOS (p=0.56), phospho-eNOS(ser 1177)(p=0.21), in levels of oxidative stress or apoptosis.
Conclusions: Microvessel reactivity was less dysfunctional at 7 weeks when compared to 4 weeks post-ischemia. The 7 week group had an increase in protective proteins HSP90 and phospho-Erk 1/2(Thr185/Tyr187). Expression of angiogenic proteins Dll4, VEGF, FGF, and eNOS were similar between 7 and 4 weeks. Thus, normal myocardium adjacent to an ischemic area develops dysfunctional microvascular responses that improve over time, expresses protective proteins, but does not contribute to native angiogenesis.