| Objective:To investigate the effects and mechanism of isometric exercise training on coronary arteriogenesis in canine model of chronic ischemic myocardium.Method:An ameroid constrictor was placed around the left anterior decending branch of the left coronary artery in healthy adult male canine.The animals were randomly divided into four groups:sham-operated group (SO) (n=6), only myocardial ischaemia group (OMI) (n=6),passive isometric exercise training group (PIE) (n=6), active isometric exercise training group (AIE) (n=6). Canine in the PIE group performed passive isometric exercises for 6 weeks. Canine in the AIE group performed active isometric exercises for 6 weeks,whereas canine in the SO group and OMI group remained sedentary.At the endpoint, Electrocardiogram and coronary angiography were used to confirm the establishment of myocardial ischemia model. SPECT (single-photonemission computed tomography) imaging was used to evaluate myocardial perfusion. Myocardial blood flow of ischemic area was measured by colored microspheres.Rentrop score was used to evaluate the formation of collateral circulation by coronary angiography.Digital subtraction angiography and CFD were used to calculate the values of WSS and blood pressure was recorded.WSS and blood pressure were also measured before,during and after IE exercise in PIE group. The expression of arteriolar density,the proliferation of mononuclear phagocyte,smooth muscle cells and endothelial cells were measured by immunohistochemical analysis.Results:①Compared with the other three groups (AIE,PIE,OMI),SO group had the lowest summed rest score (p<0.05).The score in the AIE group was much lower than that in the OMI group (p<0.05).The score in the PIE group was lower than that in the OMI group.The score of AIE was lower (25.33±7.89) than that in PIE (26.83±5.47),but there was no significant difference of summed rest score between PIE and AIE.②Rentrop score in AIE training group was higher than those in the OMI (p<0.05) and SO group (p<0.05).Rentrop score in the PIE group was higher than that in the OMI (p<0.05) and SO group (p<0.05). Rentrop score in OMI was higher than that in SO (p<0.05).Rentrop score in AIE (2.67±0.52) was higher than that in PIE (2.50±0.55),but there was no significant difference of Rentrop score between AIE and PIE (P>0.05).③The AD in AIE training group was the highest in the four groups. The AD in PIE was significant higher than those in the OMI (p<0.05),SO (p<0.05).The AD in OMI was higher than that in SO grorup (p<0.05).④The CBF in AIE group was the highest in the four groups. The CBF in PIE group was markedly higher than those in OMI (p<0.05) and SO (p<0.05).The CBF in OMI (p<0.05) was higher than that in SO (p<0.05).⑤EC number in AIE group was the highest in the four groups. EC number in PIE group was significant higher than those in OMI (p<0.05) and SO (p<0.05). EC number in OMI was higher than that in SO (p<0.05).⑥SMC number in AIE group was the highest in the four groups. SMC number in PIE was higher than those in OMI (p<0.05) and SO (p<0.05). SMC number in OMI was higher than that in SO (p<0.05).⑦The MP number in AIE group was the highest in the four groups. MP number in PIE was higher than those in OMI (p<0.05) and SO (p<0.05).MP number in OMI was higher than that in SO (p<0.05).⑧The WSS value in the AIE group was the highest in the four groups. WSS value in PIE was higher than those in OMI (p<0.05) and SO (p<0.05). WSS value in OMI was higher than that in SO (p<0.05). WSS value during IE was the highest than those before IE(p<0.05) and after IE (p<0.05).WSS value after IE was higher than that before IE (p<0.05). The SBP value during IE was the highest than those before IE (p<0.05) and after IE(p<0.05).SBP value in 30s after IE ended was higher than that in 30s before IE started (p<0.05).⑨The SBP in the SO group was the lowest in the four groups. There was no significant difference of SBP between OMI, PIE and AIE group.The DBP in AIE group was the highest in the four groups. The DBP in PIE was higher than those in SO (p<0.05) and OMI (p<0.05).The DBP in OMI was higher than that in SO (p<0.05). SBP during IE was the highest than those before IE (p<0.05) and after IE (p<0.05)SBP after IE was higher than that before IE(p<0.05). DBP during IE was the highest than those before IE (p<0.05) and after IE (p<0.05). DBP after IE was higher than that before IE (p<0.05).⑩Correlation Analysis:a.correlation of arteriogenesis and blood perfusion:The collateral blood flow was highly correlated with arteriolar density (r=0.8272, p<0.0001). The Rentrop score was moderately positive correlation correlated with arteriolar density (r=0.6723,p=0.002). b.correlation of arteriogenesis and cytological indexes:The arteriolar density was highly correlated with the EC count (r=0.8566, p＜0.0001), SMC count (r=0.8545,p<0.0001) and MP count (r=0.8055, p＜0.0001). c.correlation of arteiogenesis,blood perfusion and WSS:The arteriolar density was moderately positive correlation with WSS (r=0.6582,p=0.003). The collateral blood flow was highly correlated with WSS (r=0.7112,p=0.0009). d.correlation of WSS and cytological indexes:The EC count, SMC count and MP count were highly correlated with WSS (r=0.8770, r=0.8717 and r=0.8024, respectively, p＜0.0001).e.correlation of WSS and blood pressure:In the PIE group,the WSS was highly correlated with the SBP (r=0.8389,p<0.0001).The WSS value was moderately positive correlation with DBP(r=0.7499,p=0.0003).Conclusion:Isometric exercise could promote the formation of collateral arteries in chronic coronary stenosis model by increasing blood pressure and enhance wall shear stress.Compared with PIE, AIE was more effective. |
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