Background Enhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor ...Background Enhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34^+, CD29^+, and CD106^+. Methods Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n=6), hypercholesterolemic diet (CHOL, n=-6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n=6), and hypercholesterolemic diet with EECP treatment (EECP, n=6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor l a (SDF-1α) in porcine myocardium were assessed, respectively. Results A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3±5.6) pg/ml at week 15 vs (26.2±3.7) pg/ml at week 12, P 〈0.05, and (46.9±6.1) pg/ml at week 18 vs (26.2±3.7) pg/ml at week 12, P 〈0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150±13.9) pg/ml at week 18 vs (24.8±5.4) pg/ml at week 12, P 〈0.01). Compared to other groups and other time points, progenitor celt counts increased significantly after 2-hour EECP treatment (108±13 vs 26±6 per 10^5 leukocytes, P 〈0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180±21 vs 25±7 per 10s leukocytes, P 〈0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1α and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups. Conclusions The results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1α.展开更多
Enhance extemal counterpulsation (ECP) procedure has exhbited itself to be an effective therapy for the m anagem entof ischem ic card iovascu lar diseases, However, considering that EECP significantly increases the...Enhance extemal counterpulsation (ECP) procedure has exhbited itself to be an effective therapy for the m anagem entof ischem ic card iovascu lar diseases, However, considering that EECP significantly increases the acute diastolic pressure, whether it will intervene in the chronic progression of advanced plaque causing great concern in clilical applkation, but yet rein ains elusive presently. In the current paper, a flu id-structure interface (FSI) num erical model of artery with p iaque corn ponent w as developed based on in vivo hem odynam ic m easurem entperfotm ed h a porcine model, to caku late the m echanical stresses of the plaque before and during EECP, and h lum to assess the potential effects of long-term EECP treatm ent on plaque progression. The resu Its show that E E C P augm ented the wall shear stress (WSS) and plaque w all stress (PWS) over the card lac cycles, aswell as the spacial oscillatory of W SS (WSSG ). Durhg EECP treatm ent, the PW S level respectively raised 6.82% and 6.07% in two simulation cases. The currentpilot study suggests that E E C P treatm entre ay p lay a positive effect on inh biting the conthued plaque progression by hcreashg the PW S level over the card iac cycles. Meanwhile, the plaque morphology should be taken into consideration while m aking patient- specific plan for Ion g- term E E C P treatment in clinic.展开更多
To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors ...To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors during the atherosclerotic progress, a comprehensive study combining long-term animal experiment and numerical solving was conducted in this paper. An experimentally induced hypercholesterolemic porcine model was developed and the chronic EECP intervention was subjected. Basic hemodynamic measurement was performed in vivo, as well as the arterial endothelial samples were extracted for physiological examination. Meanwhile, a numerical model was introduced to solve the complex hemodynamic factors such as WSS and OSI. The results show that EECP treatment resulted in significant increase of the instant levels of arterial WSS, blood pressure, and OSI. During EECP treatment, the instant OSI level of the common carotid arteries over cardiac cycles raised to a mean value of 8.58 ×10-2±2.13 ×10-2. Meanwhile, the chronic intervention of EECP treatment significantly reduced the atherosclerotic lesions in abdominal aortas and the endothelial cellular adherence. The present study suggests that the unique blood flow pattern induced by EECP treatment and the augmentation of WSS level in cardiac cycles may be the most important hemodynamic mechanism that contribute to its anti-atherogenesis effect. And as one of the indices that cause great concern in current hemodynamic study, OSI may not play a key role during the initiation of atherosclerosis.展开更多
基金This study was supported by grants from tile China National 10th Five-year Key Research Project of Science (No. 2001BA706B-07) and National Natural Science Foundation of China (No. 30127001).Acknowledgement: The authors would like to thank FAN Dian-qiu, FENG Min-zhe, LIN Gui-fan, QIAN Yue-tao, DAI Gang and LIAN Lu-guang for their technical supports.
文摘Background Enhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34^+, CD29^+, and CD106^+. Methods Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n=6), hypercholesterolemic diet (CHOL, n=-6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n=6), and hypercholesterolemic diet with EECP treatment (EECP, n=6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor l a (SDF-1α) in porcine myocardium were assessed, respectively. Results A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3±5.6) pg/ml at week 15 vs (26.2±3.7) pg/ml at week 12, P 〈0.05, and (46.9±6.1) pg/ml at week 18 vs (26.2±3.7) pg/ml at week 12, P 〈0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150±13.9) pg/ml at week 18 vs (24.8±5.4) pg/ml at week 12, P 〈0.01). Compared to other groups and other time points, progenitor celt counts increased significantly after 2-hour EECP treatment (108±13 vs 26±6 per 10^5 leukocytes, P 〈0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180±21 vs 25±7 per 10s leukocytes, P 〈0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1α and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups. Conclusions The results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1α.
基金Key Clinical Project from the Ministry of Heatthgrant number:25400+1 种基金National Natural Science Foundation of Chinagrant number:81170272
文摘Enhance extemal counterpulsation (ECP) procedure has exhbited itself to be an effective therapy for the m anagem entof ischem ic card iovascu lar diseases, However, considering that EECP significantly increases the acute diastolic pressure, whether it will intervene in the chronic progression of advanced plaque causing great concern in clilical applkation, but yet rein ains elusive presently. In the current paper, a flu id-structure interface (FSI) num erical model of artery with p iaque corn ponent w as developed based on in vivo hem odynam ic m easurem entperfotm ed h a porcine model, to caku late the m echanical stresses of the plaque before and during EECP, and h lum to assess the potential effects of long-term EECP treatm ent on plaque progression. The resu Its show that E E C P augm ented the wall shear stress (WSS) and plaque w all stress (PWS) over the card lac cycles, aswell as the spacial oscillatory of W SS (WSSG ). Durhg EECP treatm ent, the PW S level respectively raised 6.82% and 6.07% in two simulation cases. The currentpilot study suggests that E E C P treatm entre ay p lay a positive effect on inh biting the conthued plaque progression by hcreashg the PW S level over the card iac cycles. Meanwhile, the plaque morphology should be taken into consideration while m aking patient- specific plan for Ion g- term E E C P treatment in clinic.
基金Key Clinical Project from the Ministry of Healthgrant number:25400+1 种基金National Natural Science Foundation of Chinagrant number:81170272
文摘To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors during the atherosclerotic progress, a comprehensive study combining long-term animal experiment and numerical solving was conducted in this paper. An experimentally induced hypercholesterolemic porcine model was developed and the chronic EECP intervention was subjected. Basic hemodynamic measurement was performed in vivo, as well as the arterial endothelial samples were extracted for physiological examination. Meanwhile, a numerical model was introduced to solve the complex hemodynamic factors such as WSS and OSI. The results show that EECP treatment resulted in significant increase of the instant levels of arterial WSS, blood pressure, and OSI. During EECP treatment, the instant OSI level of the common carotid arteries over cardiac cycles raised to a mean value of 8.58 ×10-2±2.13 ×10-2. Meanwhile, the chronic intervention of EECP treatment significantly reduced the atherosclerotic lesions in abdominal aortas and the endothelial cellular adherence. The present study suggests that the unique blood flow pattern induced by EECP treatment and the augmentation of WSS level in cardiac cycles may be the most important hemodynamic mechanism that contribute to its anti-atherogenesis effect. And as one of the indices that cause great concern in current hemodynamic study, OSI may not play a key role during the initiation of atherosclerosis.