Number Of Collateral Arteries Research Articles

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN Patients with Intermittent Claudication Injected with ALDH Bright Cells (PACE) Trial

Local injection of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells (in the dosage and manner described) into the thigh and calf of patients with claudication does not improve peak walking disease (PWT) or magnetic resonance imaging (MRI) capillary perfusion nor were there demonstrated quality of life (QOL) improvements. In patients with completely occluded superficial femoral arteries, the number of collateral arteries did increase with ALDHbr cell injection on post hoc analysis, which suggests a potential benefit in those with more advanced disease.

Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex

Hypertension is associated with chronic vascular inflammation. We tested the hypothesis that the sensitivity to develop hypertension and vascular remodeling depends on the immunological background. Blood pressure, vascular remodeling, endothelial function, vascular architecture (number of collateral arteries), and expression of inflammatory cytokines were determined in mice that received N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthesis. We studied C57BL/6, BALB/c, and BALB.B6-Cmv1r mice, a congenic strain where the natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c background. During a 4-wk treatment with l-NAME, blood pressure initially increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice showed a significant increase in mean arterial blood pressure (+53 mmHg; P < 0.001) and small artery inward remodeling. Endothelial function and vascular design were significantly different between C57BL/6 mice and BALB/C mice. The inflammatory response was similar in C57BL/6 and BALB/C mice, except for the leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the recruitment of NK cells in C57BL/6 mice. Congenic BALB.B6-Cmv1r mice showed the same endothelial response and vascular architecture as BALB/c mice. However, BALB.B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex as an important determinant in the genetically determined sensitivity to develop l-NAME-induced hypertension in mice.

Individualized approach to the surgical treatment of tetralogy of Fallot with pulmonary atresia

Tetralogy of Fallot with pulmonary atresia is a heterogeneous group of defects, characterised by diverse sources of flow of blood to the lungs, which often include multiple systemic-to-pulmonary collateral arteries. Controversy surrounds the optimal method to achieve a biventricular repair with the fewest operations while basing flow to the lungs on the native intrapericardial pulmonary arterial circulation whenever possible. We describe an individualized approach to this group of patients that optimizes these variables. Over a consecutive 10-year period, we treated 66 patients presenting with tetralogy of Fallot and pulmonary atresia according to the source of the pulmonary arterial flow. Patients were grouped according to whether the flow of blood to the lungs was derived exclusively from the intrapericardial pulmonary arteries, as seen in 29 patients, exclusively from systemic-to-pulmonary collateral arteries, as in 5 patients, or from both the intrapericardial pulmonary and collateral arteries, as in the remaining 32 patients. We divided the latter group into 9 patients deemed simple, and 23 considered complex, according to whether the pulmonary arterial index was greater than or less than 90 millimetres squared per metre squared, and whether the number of collateral arteries was less than or greater than 2, respectively. We achieved complete biventricular repair in 58 patients (88%), with an overall mortality of 3%. Repair was accomplished in a single stage in all patients without systemic-to-pulmonary collateral arteries, but was staged, with unifocalization, in the patients lacking intrapericardial pulmonary arteries. Complete repair without unifocalization was achieved in all patients with the simple variant of the mixed morphology, and in 56% of patients with the complex variant. The average number of procedures per patient to achieve complete repair was 1, 2.2, 3.8, and 2.6 in patients with exclusively native intrapericardial, simple and mixed, complex and mixed and exclusively collateral pulmonary arterial flow, respectively. An individualized approach based on the morphology of the pulmonary arterial supply permits achievement of a high rate of complete intracardiac repairs, basing pulmonary arterial flow on the intrapericardial pulmonary arteries in the great majority of cases, and has a low rate of reoperation and mortality.

Dynamic contrast‐enhanced MRI of muscle perfusion combined with MR angiography of collateral artery growth in a femoral artery ligation model

To assess the use of MRI for evaluating changes in muscle blood flow and number of collateral arteries, serial dynamic contrast-enhanced MRI (DCE-MRI) was combined with high-spatial-resolution contrast-enhanced MR angiography (MRA) in a peripheral ischemia model. The combined MRI (DCE-MRI and MRA) protocol was performed serially in 15 male rabbits at 2 h (day 0(+)), 7 days, and 21 days after femoral artery ligation. In the anterior tibial and soleus muscle, changes in resting muscle blood flow determined as the endothelial transfer coefficient (K(trans)) and arterial inflow delay from DCE-MRI and changes in the number of sub-millimeter sized collateral arteries as scored with MRA were measured. Directly after ligation, K(trans) in the anterior tibial muscle was reduced to 23% of that in the control limb, then recovered to 81% on day 7, and to 85 % on day 21. K(trans) in the soleus muscle recovered from a reduction to 63% on day 0(+), to 85% on day 7, and to 90% on day 21. The number of collaterals around the ligated femoral artery increased from 1.1 on day 0(+) to 4.2 on day 7, and 6.0 on day 21 in the ligated limb only. Combined DCE-MRI and MRA allows non-invasive serial monitoring of changes in muscle blood flow and growth of sub-millimeter sized collateral arteries in a rabbit femoral artery ligation model.

Bronchial Artery Embolization in Adults with Cystic Fibrosis: Impact on the Clinical Course and Survival

Although bronchial artery embolization (BAE) is effective in the acute control of recurrent or major hemoptysis in adults with cystic fibrosis, outcomes after embolization are not well known. The objective of this retrospective study was to evaluate respiratory function, survival, and hemoptysis-free survival in adult patients with cystic fibrosis treated for hemoptysis with BAE. Of 297 patients with cystic fibrosis hospitalized from 1990 to 2004, 30 patients (mean age, 26.7+/-9.2 years) presented with major or persistent hemoptysis that required 42 BAE sessions. These patients were compared with a control group of 27 patients without hemoptysis requiring embolization who were matched for age, sex, and forced expiratory volume in 1 second (FEV1). Hemoptysis stopped within 24 hours after BAE in 96.6% of patients (n=29), and there were no major complications. The change in the slope of FEV1 after the BAE or matching date was significantly worse in the embolization group (P=.0007). At last follow-up, nine and one patients, respectively, had undergone lung transplantation in the BAE and control groups (P=.002). The 5-year survival rates without lung transplantation were 31% and 84%, respectively, in the BAE and control groups (hazard ratio, 5.95; P=.002). Sixty-two percent of patients were free of hemoptysis 5 years after BAE. The number of collateral arteries was the only factor associated with the risk of death or recurrent hemoptysis (P=.001). Despite the effectiveness of embolization in controlling recurrent or major hemoptysis, adults with cystic fibrosis who have undergone BAE for hemoptysis are at much higher risk of respiratory function aggravation, death, and the need for lung transplantation than those who have not undergone BAE for hemoptysis. They are more likely to die or to undergo lung transplantation than to present with recurrent major hemoptysis.

Anti-tumor necrosis factor-α therapies attenuate adaptive arteriogenesis in the rabbit

The specific antagonists of tumor necrosis factor-alpha (TNF-alpha), infliximab and etanercept, are established therapeutic agents for inflammatory diseases such as rheumatoid arthritis and Crohn's disease. Although the importance of TNF-alpha in chronic inflammatory diseases is well established, little is known about its implications in the cardiovascular system. Because proliferation of arteriolar connections toward functional collateral arteries (arteriogenesis) is an inflammatory-like process, we tested in vivo the hypothesis that infliximab and etanercept have antiarteriogenic actions. Sixty-three New Zealand White rabbits underwent femoral artery occlusion and received infliximab, etanercept, or vehicle according to clinical dosage regimes. After 1 wk, collateral conductance, assessed with fluorescent microspheres, revealed significant inhibition of arteriogenesis (collateral conductance): 52.4 (SD 8.1), 35.2 (SD 7.7), and 33.3 (SD 10.1) ml x min(-1) x 100 mmHg(-1) with PBS, infliximab, and etanercept, respectively (P < 0.001). High-resolution angiography showed no significant differences in number of collateral arteries, but immunohistochemical analysis demonstrated a decrease in mean collateral diameter, proliferation of vascular smooth muscle cells, and reduction of leukocyte accumulation around collateral arteries in treated groups. Infliximab and etanercept bound to infiltrating leukocytes, which are important mediators of arteriogenesis. Infliximab induced monocyte apoptosis, and neither substance affected monocyte expression of the adhesion molecule Mac-1. We demonstrated that TNF-alpha serves as a pivotal modulator of arteriogenesis, which is attenuated by treatment with TNF-alpha inhibitors. Reduction of collateral conductance is most likely due to inhibition of perivascular leukocyte infiltration and subsequent lower vascular smooth muscle cell proliferation. This is the first report showing a negative influence of TNF-alpha inhibitors on collateral artery growth.

Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hind limb ischemia

Although nitric oxide (NO) has a critical role in angiogenesis, the therapeutic potential of NO synthase overexpression in severe ischemia remains undefined. We tested the hypothesis that overexpression of endothelial NO synthase (eNOS) would improve tissue perfusion in severe hind limb ischemia. Severe hind limb ischemia was induced in 122 adult male Sprague-Dawley rats. Ten days after the induction of hind limb ischemia, vascular isolation and intraarterial delivery of an adenoviral vector encoding eNOS (AdeNOS), a control adenoviral vector (AdE1), or phosphate-buffered saline solution (PBS) was performed. Skeletal muscle blood flow, muscle oxygen tension, angiography, and immunohistochemistry for capillary counts were measured. Gene transfer of AdeNOS increased eNOS protein expression and enzyme activity. Two weeks after gene transfer, skeletal muscle blood flow was fourfold higher in eNOS-transduced than in AdE1-transduced or PBS treated rats and was similar to exercise-induced maximal flow in nonischemic muscle. eNOS overexpression increased muscle oxygen tension in a titer-dependent fashion. This increase persisted 1 month after transduction, even though eNOS enzyme activity had declined to normal levels. Angiography and capillary counts showed that eNOS overexpression increased the size and number of collateral arteries, but did not significantly increase the capillary-muscle fiber ratio. eNOS overexpression in an ischemic rat hind limb significantly increased skeletal muscle blood flow, muscle oxygen tension, and collateral arteries (arteriogenesis). Furthermore, eNOS overexpression did not result in capillary angiogenesis above control levels. These studies demonstrate the potential for eNOS overexpression as treatment for severe limb ischemia in human beings.

Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ.

Recent studies have suggested the therapeutic potential of vascular endothelial growth factor (VEGF) gene therapy in ischemic skeletal muscle. However, only limited information is available about the effects of VEGF gene therapy in different regions of ischemic limbs, effects of control adenoviruses, and biodistribution of the transgenes after intramuscular (i.m.) administration. Here we studied angiogenesis and side effects of adenovirus-mediated VEGF and beta-galactosidase (LacZ) gene transfers in ischemic rabbit hindlimbs. Ten days after induction of ischemia, rabbits were treated with i.m. injections of saline, LacZ adenovirus (AdLacZ; 2x10(10) pfu) or adenovirus encoding mouse VEGF(164) (AdVEGF; 2x10(10) pfu). In rabbits treated with AdVEGF an increase in serum VEGF(164) levels was detected by ELISA three and seven days after the gene transfer. 30 days after the gene transfer a positive effect on capillary density was observed in the thigh region both in rabbits treated with AdVEGF and AdLacZ compared with animals that received saline. On the other hand, AdVEGF and AdLacZ gene transfers had no effect on the capillary density in the calf region on day 30. A positive correlation between the capillary density and the number of collateral arteries was observed in the thigh. Hindlimb and testis edema and excess non-physiological growth of capillaries were detected as adverse effects of the AdVEGF gene therapy. Biodistribution analysis showed that the transgene was present not only in the target muscle, but also in ectopic tissues seven days after i.m. gene transfer. The results suggest that a high dose of adenoviral vector encoding either AdVEGF or AdLacZ induces angiogenesis in the rabbit hindlimb ischemia model; i.m. injection of adenovirus leads to the transfection of ectopic organs; and AdVEGF gene transfer induces edema in ischemic skeletal muscle.