Temporal and spatial changes in collateral formation and function during chronic myocardial ischemia.
BACKGROUND
We investigated time dependence and spatial progression of cardiac function and angiogenesis signaling in a porcine model of chronic myocardial ischemia.


METHODS
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.
Robich
Michael P
MP
Department of Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI, USA.
Osipov
Robert M
RM
Chu
Louis M
LM
Feng
Jun
J
Burgess
Thomas A
TA
Oyamada
Shizu
S
Clements
Richard T
RT
Laham
Roger J
RJ
Sellke
Frank W
FW
D000818:Animals; D002908:Chronic Disease; D003097:Collateral Circulation / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000503:physiopathology*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000503:physiopathology; D008833:Microcirculation / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature