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Ann Thorac Surg 2008;86:1278-1284. doi:10.1016/j.athoracsur.2008.03.035
© 2008 The Society of Thoracic Surgeons
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Original Articles: Adult Cardiac

Enhanced Perigraft Angiogenesis Prevents Prosthetic Graft Infection

Shinichi Sato, MD, PhDa, Yoshio Nitta, MD, PhDa, Yoshikatsu Saiki, MD, PhDa,*, Shunsuke Kawamoto, MD, PhDa, Atsushi Iguchi, MD, PhDa, Mitsuo Kaku, MD, PhDb, Yasuhiko Tabata, PhD, DMScc, Koichi Tabayashi, MD, PhDa

a Department of Cardiovascular Surgery, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan
b Department of Infection Control and Laboratory Diagnostics, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan
c Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

Accepted for publication March 18, 2008.

* Address correspondence to Dr Saiki, Department of Cardiovascular Surgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryomachi, Aoba-ku, Sendai, 980-8574, Japan (Email: ysaiki{at}mail.tains.tohoku.ac.jp).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: Prosthetic vascular graft infection is an unsolved fatal complication after aortic surgery. We hypothesized that increased vascularity around a prosthetic graft may exert a preventive role against bacterial infection.

Methods: Eighty-three Fischer rats were divided into five groups according to the types of subcutaneously implanted prosthetic graft and granulocyte-colony stimulating factor (G-CSF) treatment. The groups G and C had gelatin hydrogel microspheres–incorporated graft (gel graft) with or without concomitant systemic administration of G-CSF (50 µg/kg), respectively. The groups FG and F had the gel graft impregnated with 100 µg of basic fibroblast growth factor (bFGF) with or without systemic G-CSF. The group N received untreated grafts. Seven days after graft implantation, broth containing methicillin-sensitive Staphylococcus aureus (4.0 x 103 colony-forming units) was inoculated onto the graft. All the grafts and the surrounding tissues were explanted 2 days later. Quantitative culture for methicillin-sensitive Staphylococcus aureus from the grafts and histologic assessment for capillary number in the tissue were performed.

Results: Positive infection rates in the groups N, C, and G were 34.7%, 30.4%, and 15.3%, respectively; whereas those were zero in the F and FG groups. Tissue around the grafts demonstrated significantly higher number of capillaries in the groups F and FG compared with the groups C and G. The number of bacterial colonies inversely correlated with the number of capillaries around the implanted graft (r = –0.32, p < 0.05).

Conclusions: Basic fibroblast growth factor incorporated into a prosthetic graft with or without systemic G-CSF can induce angiogenesis around the graft and prevent prosthetic graft infection.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Prosthetic vascular graft infection is a challenging fatal complication after an aortic surgery [1]. The graft infection can happen during the graft implantation operation but it can also happen postoperatively through an infection such as would sepsis, periodontitis, and pneumonia [2]. To this date, there have been no established protocols of preventing the graft infection specifically.

The tissue surrounding a prosthetic graft does not generate a vascular network very well, making it difficult for immunocompetent cells and antibiotics to penetrate the infected area around the prosthetic graft. For improved mobilization of immunocompetent cells and delivery of therapeutic antibiotics, the omental transfer and pectoral muscle flap techniques are often employed as a treatment of graft infection, leveraging capillary richness of omentum and pectoral muscles [3]. A vacuum-assisted wound closure system accelerates wound healing by enhancing angiogenesis and microcirculation in the tissue around an infected site [4, 5]. We believe that the vascularity around a prosthetic material is a key for subsequent susceptibility to an infection. We looked for a way of de novo angiogenesis around a prosthetic vascular graft.

Developments in the field of the regenerative medicine have recently made it possible to construct vascular networks in vitro and in vivo [6]. Genes to encode angiogenic factors such as vascular endothelial growth factor and recombinant human basic fibroblast growth factor (bFGF) can be introduced to human ischemic limbs [7–9]. Angiogenesis can be induced; local administration of biodegradable gelatin hydrogel microspheres containing bFGF resulted in creation of vascular networks [10–12]. Endothelial progenitor cells derived from bone marrow can migrate into ischemic tissues and promote angiogenesis when granulocyte colony-stimulating factor (G-CSF) is applied [13]. Both bFGF and G-CSF seem effective for angiogenesis, although these approaches have been used primarily for ischemic organs so far [14, 15].

Based on these findings, we hypothesized that sustained release of bFGF from gelatin hydrogel microspheres–incorporated prosthetic vascular graft (gel graft) can induce angiogenesis around the graft with or without concomitant systemic administration of G-CSF. We further hypothesized that increased vascularity around the graft may exert a preventive role against bacterial infection.

The purposes of this study were (1) to determine whether capillary number is increased around a prosthetic graft by gelatin hydrogel-mediated release of bFGF with or without systemic G-CSF, and (2) to evaluate whether host resistance against prosthetic graft infection is improved by enhanced angiogenesis, using a rat model of prosthetic graft infection [16]. The use of bFGF and G-CSF to enhance angiogenesis around a prosthetic graft can be the first step toward the development of its infection prevention method.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
Male Fischer rats (Charles River Laboratories Japan, Tokyo, Japan), whose weight ranged from 150 g to 210 g, were used for this study. Rats were handled in accordance with the "Guidelines for the Care and Use of Laboratory Animals" (NIH publication 85-23, revised 1985). The experimental and animal care protocols were both approved by the Animal Care Committee at Tohoku University School of Medicine.

Rat Model of Prosthetic Graft Infection
Figure 1 shows the time schedule of this experiment. Rats were anesthetized with ketamine hydrochloride (60 mg/kg) injected intramuscularly and pentobarbital sodium (20 mg/kg) intraperitoneally, and then the back hair was shaved. A subcutaneous pocket was created to the left of the median line with a 1.5 cm incision. A 10 x 10 mm square sterile collagen-sealed woven Dacron graft (Hemashield Gold; Boston Scientific Medi-tech, Wayne, New Jersey) was implanted aseptically into the pocket, and the skin was closed with a running polypropylene suture (day 0). Seven days later, broth (Tryptone Soya Broth; Oxoid, Basingstone, Hampshire, England) containing 4.0 x 103 colony-forming units (CFU) of methicillin-sensitive Staphylococcus aureus (MSSA [no.732; Tohoku University Hospital, Sendai, Japan]) was inoculated onto the graft surface with a tuberculin syringe. The MSSA was always inoculated by the same person. Each rat was returned to and kept in its own cage to prevent infecting the others.


Figure 1
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  		Fig 1. Time schedule of the experiment. Seven days after subcutaneous implantation of a prosthetic graft impregnated with or without basic fibroblast growth factor (bFGF) and with or without systemic granulocyte-colony stimulating factor (G-CSF), inoculation of methicillin-sensitive Staphylococcus aureus (MSSA) was performed around the graft. Two days later, the graft was explanted. Viable bacteria were quantified, and the tissue around the graft was histologically assessed. (d = days after graft implantation.)

 
The graft was explanted 2 days after the MSSA inoculation (day 9) under the identical anesthetizing method used for graft implantation, and the extracted gel graft was placed in a sterile tube. The rat was then killed with the lethal dose of pentobarbital sodium. The extracted graft was first rinsed in sterile saline solution, placed in a tube containing 10 mL phosphate-buffered saline solution (PBS), and sonicated using the Bransonic ultrasonic cleaner (47 kHz; Branson Ultrasonic Division, Emerson-Japan, Tokyo, Japan) for 10 minutes to remove the bacteria adhered to the gel graft. The suspension fluid containing the bacteria separated from the graft was serially diluted 10-fold and a 50 µL sample was placed on a blood agar plate. Multiple plates were made from each suspension fluid. Each plate was incubated at 35°C for 24 hours, and the number of MSSA colony was counted for evaluation of infection control effectiveness. One colony per 50 µL is equivalent to 2.0 x 101 CFU/mL, and this was the limit of detection for this method. When bacterial colonies were observed on a plate, graft infection was judged to be positive.

Preparation of bFGF and G-CSF
This study used an aqueous solution of human recombinant bFGF (10 mg/mL), the isoelectric point 9.6, supplied by Kaken Pharmaceutical (Tokyo, Japan). Recombinant human G-CSF (Chugai Pharmaceutical, Tokyo, Japan), 100 µg, was dissolved in 10 mL PBS.

Preparation of bFGF-Impregnated Gelatin Microspheres
The gelatin (Nitta Gelatin, Osaka, Japan) was isolated from a bovine bone by an alkaline process, of which the isoelectric point was 4.9 and the molecular weight 99,000. The water content of the gelatin hydrogel was 95%, and the hydrogel was known to completely degrade in 14 days in vivo [17]. Gelatin microspheres were prepared through glutaraldehyde crosslinking of a gelatin aqueous solution [18]. The average diameter of a microsphere that was completely swelled in the saline was 32.75 µm. Basic FGF-impregnated gelatin microspheres were prepared by dropping 20 µL of the aqueous solution containing 200 µg of bFGF onto 2 mg of freeze-dried gelatin microsphere, which was kept at 4°C for 24 hours to allow bFGF to be integrated with the microspheres. The prosthetic graft was coated with this bFGF-impregnated gelatin microsperes.

Evaluation of Preventive Effect of bFGF and G-CSF on Graft Infection
Table 1 summarizes the study group in this investigation. Eighty-three rats in this study were classified into five groups (N, C, G, F, and FG) by the types of implanted grafts and G-CSF treatment: group N—an untreated prosthetic graft (non–gel graft) with no bFGF or G-CSF; group C—a prosthetic graft treated with plain gelatin hydrogel microspheres (gel graft) with no bFGF or G-CSF; group G—a plain gel graft with no bFGF and concomitant intraperitoneal administration of PBS (5 mL/kg) containing 50 µg G-CSF; group F—a gel graft impregnated with bFGF with no G-CSF; and group FG—a bFGF-impregnated gel graft and concomitant intraperitoneal administration of PBS (5 mL/kg) containing 50 µg G-CSF. The PBS (5 mL/kg) that contained no G-CSF was also injected intraperitoneally into groups N, C, and F to neutralize the impact of PBS.


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  		Table 1 Groups Included in the Study
 
Histologic Analysis
The tissues around each prosthetic graft were fixed in 10% buffered formalin and stained with hematoxylin-eosin. For immunohistochemical staining of endothelial cells, the sheep anticanine von Willebrand factor (vWF) antibodies (Cedarlane Laboratories, Ontario, Canada) were followed by biotinylated anti-sheep antibodies (Vector Laboratories, Burlingame, California). The number of capillaries (vessel diameter < 20 µm) was counted in six adjacent fields around the perigraft. The six capillary counts were averaged for each subject rat. These histologic analyses were performed by two blinded observers.

Leukocyte Count After G-CSF Injection
To evaluate the leukocyte mobilization effect of G-CSF, an additional 12 rats were intraperitoneally injected with 50 µg/kg G-CSF, and their blood samples were collected from the left ventricle of the heart of each rat for the leukocyte count on days 0, 1, 3, and 7.

Statistical Analysis
For statistical analyses, Excel for Mac with the add-in software module called StatMate III (ATMS, Tokyo, Japan) was used. The Welch test was used for the leukocyte count analysis. Fisher's exact probability test was used for the comparison of positive infection rates. The Kolmogorov-Smirnov test was used for the analysis of capillary count distribution, and Student's t test was used for its statistical significance between two targeted groups. The correlation between the capillary count and the bacterial colony count was performed with the Spearman's rank correlation test. The p value less than 0.05 determined the statistical significance.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Preliminary Monitoring Leukocyte Count After Injection of G-CSF
The number of circulating leukocytes significantly increased on the following day of G-CSF injection (day 1) compared with the day of injection (day 0 [4,800 ± 260/µL versus 3,200 ± 700/µL, p < 0.05]), and returned to the baseline level on day 3. By the time MSSA was injected into the rats of the study groups, the effects of G-CSF to stimulate leukocyte generation had been diminished.

MSSA Colony Count and Positive Infection Rate
Figure 2 shows the colony counts of MSSA isolated from the explanted prosthetic grafts. The infection rate of each group is plotted in Figure 3. The infection rates of the groups N, C, and G were 34.7%, 30.4%, and 15.3%, respectively, and those of the F and FG groups were zero.


Figure 2
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  		Fig 2. Quantification of viable methicillin-sensitive Staphylococcus aureus on the explanted grafts. Immediately after the explantation of the graft, quantitative culture was performed. (C = gelatin hydrogel microspheres–incorporated prosthetic graft without basic fibroblast growth factor [bFGF] and granulocyte-colony stimulating factor [G-CSF]; CFU = colony-forming unit; F = gelatin hydrogel microspheres–incorporated prosthetic graft with bFGF without systemic G-CSF; FG = gelatin hydrogel microspheres–incorporated prosthetic graft both with bFGF and systemic G-CSF; G = gelatin hydrogel microspheres–incorporated prosthetic graft without bFGF with simultaneous systemic administration of G-CSF; N = untreated graft.)

 

Figure 3
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  		Fig 3. Infection rate of the explanted graft. When a colony of methicillin-sensitive Staphylococcus aureus was detected by culture, infection was judged as positive. Positive infection was observed in groups N, C, and G, whereas bacterial colony was not detected in groups F and FG.. The differences between the groups FG and N along with C were statistically significant. (C = gelatin hydrogel microspheres–incorporated prosthetic graft without basic fibroblast growth factor [bFGF] and granulocyte-colony stimulating factor [G-CSF]; CFU = colony-forming unit; F = gelatin hydrogel microspheres–incorporated prosthetic graft with bFGF without systemic G-CSF; FG = gelatin hydrogel microspheres–incorporated prosthetic graft both with bFGF and systemic G-CSF; G = gelatin hydrogel microspheres–incorporated prosthetic graft without bFGF with simultaneous systemic administration of G-CSF; N = untreated graft.)

 
Capillary Count
Figure 4 shows the capillary counts. The capillary counts of the tissue around the graft of groups F and FG were significantly higher than that of groups C and G. The capillary count and the colony count are plotted in Figure 5. The statistical analysis showed that the capillary count and the colony count were inversely correlated (r = –0.32, p < 0.05; see Fig 5). The regression line using the natural logarithm of the number of colonies as outcome variable (log10Y) and the number of capillaries as predictor variable (X) was log10Y = 1.768 – 0.05261X (p < 0.05).


Figure 4
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  		Fig 4. Number of capillaries observed on the histologic sections. Capillaries were counted at the adjoining six fields of the central zone of each section with magnification of x100. The upper and lower edges of each box plot indicate the 25th and 75th percentiles, the "whiskers" the 10th and 90th percentiles, the solid horizontal line the median. All outliers are shown as individual data points. The groups F and FG had significantly higher number of capillaries compared with the groups C and G. (C = gelatin hydrogel microspheres–incorporated prosthetic graft without basic fibroblast growth factor [bFGF] and granulocyte-colony stimulating factor [G-CSF]; CFU = colony-forming unit; F = gelatin hydrogel microspheres–incorporated prosthetic graft with bFGF without systemic G-CSF; FG = gelatin hydrogel microspheres–incorporated prosthetic graft both with bFGF and systemic G-CSF; G = gelatin hydrogel microspheres–incorporated prosthetic graft without bFGF with simultaneous systemic administration of G-CSF; N = untreated graft.)

 

Figure 5
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  		Fig 5. Correlation between the number of colonies and the number of capillaries. The number of colonies was inversely correlated with the number of capillaries (r = –0.32, p < 0.05). Note that there were no colonies detected when the number of capillaries exceeded 22 per field with magnification x100. (C = gelatin hydrogel microspheres–incorporated prosthetic graft without basic fibroblast growth factor [bFGF] and granulocyte-colony stimulating factor [G-CSF]; CFU = colony-forming unit; F = gelatin hydrogel microspheres–incorporated prosthetic graft with bFGF without systemic G-CSF; FG = gelatin hydrogel microspheres–incorporated prosthetic graft both with bFGF and systemic G-CSF; G = gelatin hydrogel microspheres–incorporated prosthetic graft without bFGF with simultaneous systemic administration of G-CSF; N = untreated graft.)

 
Histologic Analysis
The tissue samples around the perigraft were taken after the subject rats were killed and photographed (Fig 6). The increase of capillaries was visually noticeable in groups F and FG. This observation was confirmed with the stained tissues by immunohistochemical staining using vWF antibodies (Fig 7).


Figure 6
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  		Fig 6. Representative photographs of histologic sections of the tissue around the graft obtained 2 days after inoculation with methicillin-sensitive Staphylococcus aureus. Note that groups F and FG have marked increase in the number of newly formed vessels compared with groups N, C, and G. (Hematoxylin-eosin staining; original magnification x100. Scale bar represents 100 µm.) (C = gelatin hydrogel microspheres–incorporated prosthetic graft without basic fibroblast growth factor [bFGF] and granulocyte-colony stimulating factor [G-CSF]; F = gelatin hydrogel microspheres–incorporated prosthetic graft with bFGF without systemic G-CSF; FG = gelatin hydrogel microspheres–incorporated prosthetic graft both with bFGF and systemic G-CSF; G = gelatin hydrogel microspheres–incorporated prosthetic graft without bFGF with simultaneous systemic administration of G-CSF; N = untreated graft.)

 

Figure 7
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  		Fig 7. Immunohistochemical stain for endothelial cell with von Willebrand factor. The vessels detected by hematoxylin-eosin stain were confirmed to have von Willebrand factor positive endothelial cells. (Original magnification x200. Scale bar represents 50 µm.) (C = gelatin hydrogel microspheres–incorporated prosthetic graft without basic fibroblast growth factor [bFGF] and granulocyte-colony stimulating factor [G-CSF]; F = gelatin hydrogel microspheres–incorporated prosthetic graft with bFGF without systemic G-CSF; FG = gelatin hydrogel microspheres–incorporated prosthetic graft both with bFGF and systemic G-CSF; G = gelatin hydrogel microspheres–incorporated prosthetic graft without bFGF with simultaneous systemic administration of G-CSF; N = untreated graft.)

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
We have demonstrated that sustained release of bFGF from gelatin hydrogel microspheres–incorporated prosthetic Dacron graft can induce angiogenesis around the graft with or without concomitant systemic administration of G-CSF. We have also shown that increased vascularity around the graft can exert a preventive role against bacterial infection. Since there have been no established measures to specifically prevent graft infection, our approach to enhance angiogenesis around a prosthetic graft can be the first step to develop a procedure to prevent graft infection.

For prevention of graft infections in a clinical setting, a rifampicin-bonding technique is said to be effective in some reports [19]. We have tried this technique and found that occasionally rifampicin was washed away by blood in the operative field or by saline irrigation because of the hydrophilic nature of the antibiotics. This method is, therefore, considered effective for the prevention of intraoperative contamination of the prosthetic graft. A graft infection can happen any time after aortic surgery [2, 20], and strategic midterm and long-tem approaches to reduce a graft infection are warranted.

Recently, Sakaguchi and associates [21] reported that slowly released vancomycin was effective in preventing a prosthetic graft infection. Unlike the intraoperative use of rifampicin, the effectiveness of the antibiotics against bacterial infections lasts longer because of its sustained slow release. But a single antibiotic has a limited bacterial sensitivity spectrum. The sustained release might cause a resistance of the micro-organism after an extended use. Our approach to enhance angiogenesis around a prosthetic graft that does not use antibiotics is applicable to a broad spectrum of bacteria and is less likely to induce bacterial alteration. Hirose and colleagues [22] reported that the tissue regeneration enhanced by bFGF was effective to reduce catheter-related infections in a mice model, and that is essentially compatible with our results.

We report that clearly demonstrated "de novo" enhanced perigraft angiogenesis can suppress prosthetic graft infection. Both bFGF and G-CSF have multimodal physiologic effects. For instance, bFGF has angiogenic activity, works as a potent mitogen for cells of mesodermal and neuroectodermal origin, and promotes survival of many types of cell [23–25]. Likewise, G-CSF has been reported to increase the number of circulating neutrophils and activate them. In addition, G-CSF enhances the recruitment of bone marrow–derived endothelial progenitor cells, facilitates their migration, and promotes angiogenesis [13, 26]. Hence, the single action of these agents may not solely be attributable to a prophylactic effect on graft infection. Nevertheless, the inverse relation between the bacterial colony number and capillary number observed in our present study indicates direct evidence for angiogenesis on suppression of bacterial infection. Of note, when the capillary number per field (x100 magnification) exceeded 22, there was no bacterial colony detected from any groups, including control (Fig 5).

Advantages of the use of bFGF and G-CSF are that both agents are already clinically available and their safety in use and potential adverse effects have been well established, and that may facilitate the introduction of our approach to the clinical arena. With regard to how we clinically apply our strategy, incubation of an entire prosthetic graft with bFGF before implantation is certainly the one of the options. Alternatively, wrapping around the grafts with a biodegradable sheet impregnated with bFGF may allow slow release of the agent. Although a synergistic effect of G-CSF on enhanced angiogenesis was not clearly defined in our present study, we suspect that the dose of G-CSF might not be optimal to observe its effect. Clinically, G-CSF is usually given in multiple doses, whereas we administered a single dose in our experimental protocol to minimize the invasiveness to the animals. Alteration in the dose of systemic G-CSF is warranted to advance our therapeutic strategy.

To examine the effect of simultaneous, not preceding, construction of a vascular network on the prevention of intraoperative infection, we performed a different set of experiments in which we inoculated MSSA at the time of graft implantation. Impregnation of bFGF and systemic G-CSF failed to suppress graft infection in that model. Based on these findings, we believe that prophylactic and preceding construction of a vascular network around the graft is crucial to prevent graft infection.

Study Limitations
First, we used a subcutaneous infection model using rats to evaluate graft infection under variable conditions. Because the blood contact may alter the response to bFGF impregnated onto the prosthetic graft, a model with vascular replacement may be warranted. Second, the animals were followed for a period of 9 days; hence, the long-term consequences in the vascular network are unknown.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
The authors wish to express their appreciation to Drs Keiji Kanemitsu, Hiroyuki Kunishima, and Ken Inden, and to Ms Michiko Saito for their kind technical support in the microbiological maneuver, to Ms Hiromi Fuji and Yayoi Takahashi for excellent histologic preparation, to Ms Tomomi Kibushi for professional coordination in the animal facility, and to Dr Masako Komatsu for advice on statistical analysis.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Coselli JS, Köksoy C, LeMaire SA. Management of thoracic aortic graft infections Ann Thorac Surg 1999;67:1990-1993.[Abstract/Free Full Text]
  2. LeMaire SA, Coselli JS. Options for managing infected ascending aortic grafts J Thorac Cardiovasc Surg 2007;134:839-843.[Free Full Text]
  3. Shrager JB, Wain JC, Wright CD, et al. Omentum is highly effective in the management of complex cardiothoracic surgical problems J Thorac Cardiovasc Surg 2003;125:526-532.[Abstract/Free Full Text]
  4. Saiki Y, Hata M, Akasaka J, Saito T, Tabayashi K. Vacuum-assisted closure system for the treatment of mediastinitis after total aortic arch replacement Jpn J Thorac Cardiovasc Surg 2005;53:638-640.[Medline]
  5. Fuchs U, Zittermann A, Stuettgen B, Groening A, Minami K, Koerfer R. Clinical outcome of patients with deep sternal wound infection managed by vacuum-assisted closure compared with conventional therapy with open packing: a retrospective analysis Ann Thorac Surg 2005;79:526-531.[Abstract/Free Full Text]
  6. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis Science 1997;275:964-967.[Abstract/Free Full Text]
  7. Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia Circulation 1998;97:1114-1123.[Abstract/Free Full Text]
  8. Lazarous DF, Unger EF, Epstein SE, et al. Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial J Am Coll Cardiol 2000;36:1239-1244.[Abstract/Free Full Text]
  9. Lederman RJ, Mendelsohn FO, Anderson RD, et al. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial Lancet 2002;359:2053-2058.[Medline]
  10. Kawai K, Suzuki S, Tabata Y, Nishimura Y. Accelerated wound healing through the incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis using a pressure-induced decubitus ulcer model in genetically diabetic mice Br J Plast Surg 2005;58:1115-1123.[Medline]
  11. Ueyama K, Bing G, Tabata Y. Development of biologic coronary artery bypass grafting in a rabbit model: revival of a classic concept with modern biotechnology J Thorac Cardiovasc Surg 2004;127:1608-1615.[Abstract/Free Full Text]
  12. Iwakura A, Tabata Y, Miyao M, et al. Novel method to enhance sternal healing after harvesting bilateral internal thoracic arteries with use of basic fibroblast growth factor Circulation 2000;102:III307-III311.[Medline]
  13. Ohki Y, Heissig B, Sato Y, et al. Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils FASEB J 2005;19:2005-2007.[Abstract/Free Full Text]
  14. Rajagopalan S, Mohler III ER, Lederman RJ, et al. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication Circulation 2003;108:1933-1938.[Abstract/Free Full Text]
  15. Liu Y, Sun L, Huan Y, Zhao H, Deng J. Effects of basic fibroblast growth factor microspheres on angiogenesis in ischemic myocardium and cardiac function: analysis with dobutamine cardiovascular magnetic resonance tagging Eur J Cardiothorac Surg 2006;30:103-107.[Abstract/Free Full Text]
  16. Ghiselli R, Giacometti A, Cirioni O, et al. Temporin A as a prophylactic agent against methicillin sodium-susceptible and methicillin sodium-resistant Staphylococcus epidermidis vascular graft infection J Vasc Surg 2002;36:1027-1030.[Medline]
  17. Tabata Y, Hijikata S, Ikada Y. Enhanced vascularization and tissue granulation by basic fibroblast growth factor impregnated in gelatin hydrogels J Control Release 1994;31:189-199.
  18. Iwakura A, Fujita M, Kataoka K, et al. Intramyocardial sustained delivery of basic fibroblast growth factor improves angiogenesis and ventricular function in a rat infarct model Heart Vessels 2003;18:93-99.[Medline]
  19. Bandyk DF, Novotney ML, Johnson BL, Back MR, Roth SR. Use of rifampin-soaked gelatin-sealed polyester grafts for in situ treatment of primary aortic and vascular prosthetic infections J Surg Res 2001;95:44-49.[Medline]
  20. Sato S, Saiki Y, Nitta Y, Oda K, Takahashi G, Tabayashi K. Redo total aortic arch replacement using an extended homograft for graft infection Jpn J Thorac Cardiovasc Surg 2006;54:448-450.[Medline]
  21. Sakaguchi H, Marui A, Hirose K, et al. Less-invasive and highly effective method for preventing methicillin-resistant Staphylococcus aureus graft infection by local sustained release of vancomycin J Thorac Cardiovasc Surg 2008;135:25-31.[Abstract/Free Full Text]
  22. Hirose K, Marui A, Arai Y, et al. A novel approach to reduce catheter-related infection using sustained-release basic fibroblast growth factor for tissue regeneration in mice Heart Vessels 2007;22:261-267.[Medline]
  23. Hayek A, Culler FL, Beattie GM, Lopez AD, Cuevas P, Baird A. An in vivo model for study of the angiogenic effects of basic fibroblast growth factor Biochem Biophys Res Commun 1987;147:876-880.[Medline]
  24. Burgess WH, Maciag T. The heparin-binding (fibroblast) growth factor family of proteins Annu Rev Biochem 1989;58:575-606.[Medline]
  25. Rifkin DB, Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor J Cell Biol 1989;109:1-6.[Free Full Text]
  26. Kocher AA, Schuster, MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function Nat Med 2001;7:430-436.[Medline]

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Invited Commentary
Hikaru Matsuda
Ann. Thorac. Surg. 2008 86: 1284-1285. [Extract] [Full Text] [PDF]



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Ann. Thorac. Surg., October 1, 2008; 86(4): 1284 - 1285.
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