BACKGROUND: We investigated time dependence and spatial progression of cardiac function and angiogenesis signaling in a porcine model of chronic myocardial ischemia. STUDY DESIGN: Yorkshire mini-swine (n = 7/group) were subjected to chronic myocardial ischemia by placing an ameroid constrictor on the left circumflex coronary artery under general anesthesia. Swine were sacrificed after either 4 or 7 weeks of ischemia. Myocardial function, angiographic evidence of angiogenesis, microvessel function, molecular signaling, and levels of apoptosis and oxidative stress were assessed. RESULTS: Flow reserve was significantly increased at 7 versus 4 weeks. Myocardial function (+dP/dt) improved 1.5-fold by 7 weeks. In the ischemic territory, microvessels at 4 weeks displayed abnormal contraction responses to serotonin, which diminished at 7 weeks. Delta-like ligand 4 protein expression decreased at 7 weeks; expression of vascular endothelial growth factor (VEGF) and phospho-endothelial nitric acid synthase (eNOS) increased. The number of apoptotic cells was decreased at 7 weeks, and antiapoptotic markers heat shock protein (HSP) 27 and HSP 90 were upregulated at 7 weeks. There was an increase in proliferating endothelial cells at 7 weeks as compared with 4 weeks. In the adjacent normal ventricle, microvessels demonstrated smaller contraction responses to endothelin-1 and serotonin at 7 weeks. There was an increase in protein peroxidation in the ischemic territory at 7 weeks. CONCLUSIONS: Over time, myocardial perfusion, function, and angiogenic signaling improved in the ischemic myocardium and adjacent normal territory compared with what is observed shortly after coronary occlusion.
BACKGROUND: We investigated time dependence and spatial progression of cardiac function and angiogenesis signaling in a porcine model of chronic myocardial ischemia. STUDY DESIGN: Yorkshire mini-swine (n = 7/group) were subjected to chronic myocardial ischemia by placing an ameroid constrictor on the left circumflex coronary artery under general anesthesia. Swine were sacrificed after either 4 or 7 weeks of ischemia. Myocardial function, angiographic evidence of angiogenesis, microvessel function, molecular signaling, and levels of apoptosis and oxidative stress were assessed. RESULTS: Flow reserve was significantly increased at 7 versus 4 weeks. Myocardial function (+dP/dt) improved 1.5-fold by 7 weeks. In the ischemic territory, microvessels at 4 weeks displayed abnormal contraction responses to serotonin, which diminished at 7 weeks. Delta-like ligand 4 protein expression decreased at 7 weeks; expression of vascular endothelial growth factor (VEGF) and phospho-endothelial nitric acid synthase (eNOS) increased. The number of apoptotic cells was decreased at 7 weeks, and antiapoptotic markers heat shock protein (HSP) 27 and HSP 90 were upregulated at 7 weeks. There was an increase in proliferating endothelial cells at 7 weeks as compared with 4 weeks. In the adjacent normal ventricle, microvessels demonstrated smaller contraction responses to endothelin-1 and serotonin at 7 weeks. There was an increase in protein peroxidation in the ischemic territory at 7 weeks. CONCLUSIONS: Over time, myocardial perfusion, function, and angiogenic signaling improved in the ischemic myocardium and adjacent normal territory compared with what is observed shortly after coronary occlusion.
Authors: Vanessa P M van Empel; Anne T Bertrand; Roel van der Nagel; Sawa Kostin; Pieter A Doevendans; Harry J Crijns; Elly de Wit; Wim Sluiter; Susan L Ackerman; Leon J De Windt Journal: Circ Res Date: 2005-06-02 Impact factor: 17.367
Authors: M Simons; R O Bonow; N A Chronos; D J Cohen; F J Giordano; H K Hammond; R J Laham; W Li; M Pike; F W Sellke; T J Stegmann; J E Udelson; T K Rosengart Journal: Circulation Date: 2000-09-12 Impact factor: 29.690
Authors: Anne Limbourg; Merlin Ploom; Diana Elligsen; Inga Sörensen; Tibor Ziegelhoeffer; Achim Gossler; Helmut Drexler; Florian P Limbourg Journal: Circ Res Date: 2007-01-18 Impact factor: 17.367
Authors: Michael P Robich; Louis M Chu; Thomas A Burgess; Jun Feng; Yuchi Han; Reza Nezafat; Michael P Leber; Roger J Laham; Warren J Manning; Frank W Sellke Journal: J Am Coll Surg Date: 2012-08-04 Impact factor: 6.113