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1.  Use of Bacteria- and Fungus-Binding Mesh in Negative Pressure Wound Therapy Provides Significant Granulation Tissue Without Tissue Ingrowth 
Eplasty  2014;14:e3.
Objective: Bacteria- and fungus-binding mesh traps and inactivates bacteria and fungus, which makes it interesting, alternative, and wound filler for negative pressure wound therapy (NPWT). The aim of this study was to compare pathogen-binding mesh, black foam, and gauze in NPWT with regard to granulation tissue formation and ingrowth of wound bed tissue in the wound filler. Methods: Wounds on the backs of 8 pigs underwent 72 hours of NPWT using pathogen-binding mesh, foam, or gauze. Microdeformation of the wound bed and granulation tissue formation and the force required to remove the wound fillers was studied. Results: Pathogen-binding mesh produced more granulation tissue, leukocyte infiltration, and tissue disorganization in the wound bed than gauze, but less than foam. All 3 wound fillers caused microdeformation of the wound bed surface. Little force was required to remove pathogen-binding mesh and gauze, while considerable force was needed to remove foam. This is the result of tissue growth into the foam, but not into pathogen-binding mesh or gauze, as shown by examination of biopsy sections from the wound bed. Conclusions: This study shows that using pathogen-binding mesh as a wound filler for NPWT leads to a significant amount of granulation tissue in the wound bed, more than that with gauze, but eliminates the problems of ingrowth of the wound bed into the wound filler. Pathogen-binding mesh is thus an interesting wound filler in NPWT.
PMCID: PMC3899807  PMID: 24501617
blood flow; experimental surgery; negative pressure wound therapy; wound contraction; wound dressing; wound healing
2.  A Short Period of Ventilation without Perfusion Seems to Reduce Atelectasis without Harming the Lungs during Ex Vivo Lung Perfusion 
Journal of Transplantation  2013;2013:729286.
To evaluate the lung function of donors after circulatory deaths (DCDs), ex vivo lung perfusion (EVLP) has been shown to be a valuable method. We present modified EVLP where lung atelectasis is removed, while the lung perfusion is temporarily shut down. Twelve pigs were randomized into two groups: modified EVLP and conventional EVLP. When the lungs had reached 37°C in the EVLP circuit, lung perfusion was temporarily shut down in the modified EVLP group, and positive end-expiratory pressure (PEEP) was increased to 10 cm H2O for 10 minutes. In the conventional EVLP group, PEEP was increased to 10 cm H2O for 10 minutes with unchanged lung perfusion. In the modified EVLP group, the arterial oxygen partial pressure (PaO2) was 18.5 ± 7.0 kPa before and 64.5 ± 6.0 kPa after the maneuver (P < 0.001). In the conventional EVLP group, the PaO2 was 16.8 ± 3.1 kPa and 46.8 ± 2.7 kPa after the maneuver (P < 0.01; P < 0.01). In the modified EVLP group, the pulmonary graft weight was unchanged, while in the conventional EVLP group, the pulmonary graft weight was significantly increased. Modified EVLP with normoventilation of the lungs without ongoing lung perfusion for 10 minutes may eliminate atelectasis almost completely without harming the lungs.
doi:10.1155/2013/729286
PMCID: PMC3786511  PMID: 24102021
3.  Pressure transduction and fluid evacuation during conventional negative pressure wound therapy of the open abdomen and NPWT using a protective disc over the intestines 
BMC Surgery  2012;12:4.
Background
Negative pressure wound therapy (NPWT) has gained acceptance among surgeons, for the treatment of open abdomen, since very high closure rates have been reported with this method, compared to other kinds of wound management for the open abdomen. However, the method has occasionally been associated with increased development of fistulae. We have previously shown that NPWT induces ischemia in the underlying small intestines close to the vacuum source, and that a protective disc placed between the intestines and the vacuum source prevents the induction of ischemia. In this study we compare pressure transduction and fluid evacuation of the open abdomen with conventional NPWT and NPWT with a protective disc.
Methods
Six pigs underwent midline incision and the application of conventional NPWT and NPWT with a protective disc between the intestines and the vacuum source. The pressure transduction was measured centrally beneath the dressing, and at the anterior abdominal wall, before and after the application of topical negative pressures of -50, -70 and -120 mmHg. The drainage of fluid from the abdomen was measured, with and without the protective disc.
Results
Abdominal drainage was significantly better (p < 0. 001) using NPWT with the protective disc at -120 mmHg (439 ± 25 ml vs. 239 ± 31 ml), at -70 mmHg (341 ± 27 ml vs. 166 ± 9 ml) and at -50 mmHg (350 ± 50 ml vs. 151 ± 21 ml) than with conventional NPWT. The pressure transduction was more even at all pressure levels using NPWT with the protective disc than with conventional NPWT.
Conclusions
The drainage of the open abdomen was significantly more effective when using NWPT with the protective disc than with conventional NWPT. This is believed to be due to the more even and effective pressure transduction in the open abdomen using a protective disc in combination with NPWT.
doi:10.1186/1471-2482-12-4
PMCID: PMC3339517  PMID: 22443416
4.  The Effects of Variable, Intermittent, and Continuous Negative Pressure Wound Therapy, Using Foam or Gauze, on Wound Contraction, Granulation Tissue Formation, and Ingrowth Into the Wound Filler 
Eplasty  2012;12:e5.
Objective: Negative pressure wound therapy (NPWT) is commonly used in the continuous mode. Intermittent pressure therapy (IPT) results in faster wound healing, but it often causes pain. Variable pressure therapy (VPT) has therefore been introduced to provide a smooth transition between 2 different pressure environments, thereby maintaining the negative pressure environment throughout the therapy. The aim of the present study was to examine the effects of IPT and VPT on granulation tissue formation. Method: A peripheral wound in a porcine model was treated for 72 hours with continuous NPWT (-80 mm Hg), IPT (0 to -80 mm Hg), or VPT (-10 to -80 mm Hg), using foam or gauze as wound filler. Wound contraction and force to remove the wound filler were measured. Biopsies from the wound bed were examined histologically for granulation tissue formation. Results: Intermittent pressure therapy and VPT produced similar results. Wound contraction was more pronounced following IPT and VPT than continuous NPWT. Intermittent pressure therapy and VPT resulted in the formation of more granulation tissue than continuous NPWT. Leukocyte infiltration and tissue disorganization were more prominent after IPT and VPT than after continuous NPWT. Granulation tissue grew into foam but not into gauze, regardless of the mode of negative pressure application, and less force was needed to remove gauze than foam. Conclusions: Wound contraction and granulation tissue formation is more pronounced following IPT and VPT than continuous NPWT. Granulation tissue grows into foam but not into gauze. The choice of negative pressure mode and wound filler is crucial in clinical practice to optimize healing while minimizing pain.
PMCID: PMC3266212  PMID: 22292101
5.  How to Recondition Ex Vivo Initially Rejected Donor Lungs for Clinical Transplantation: Clinical Experience from Lund University Hospital 
Journal of Transplantation  2011;2011:754383.
A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. We have recently reported the results of the first six double lung transplantations performed with donor lungs reconditioned ex vivo that had been deemed unsuitable for transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant organizations because the arterial oxygen pressure was less than 40 kPa. The three-month survival of patients undergoing transplant with these lungs was 100%. One patient died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are still alive and well 24 months after transplantation, with no signs of bronchiolitis obliterans syndrome. The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation circuit using STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue. Functional evaluation was performed with deoxygenated perfusate at different inspired fractions of oxygen. The arterial oxygen pressure was significantly improved in this model. This ex vivo evaluation model is thus a valuable addition to the armamentarium in increasing the number of acceptable lungs in a donor population with inferior arterial oxygen pressure values, thereby, increasing the lung donor pool for transplantation. In the following paper we present our clinical experience from the first six patients in the world. We also present the technique we used in detail with flowchart.
doi:10.1155/2011/754383
PMCID: PMC3163037  PMID: 21876780
6.  A rigid barrier between the heart and sternum protects the heart and lungs against rupture during negative pressure wound therapy 
Objectives
Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier has been suggested to offer protection against this lethal complication, by preventing the heart from being drawn up and damaged by the sharp edges of the sternum. The aim of the present study was to investigate whether a rigid barrier protects the heart and lungs against injury during NPWT.
Methods
Sixteen pigs underwent median sternotomy followed by NPWT at -120 mmHg for 24 hours, in the absence (eight pigs) or presence (eight pigs) of a rigid plastic disc between the heart and the sternal edges. The macroscopic appearance of the heart and lungs was inspected after 12 and 24 hours of NPWT.
Results
After 24 hours of NPWT at -120 mmHg the area of epicardial petechial bleeding was 11.90 ± 1.10 cm2 when no protective disc was used, and 1.15 ± 0.19 cm2 when using the disc (p < 0.001). Heart rupture was observed in three of the eight animals treated with NPWT without the disc. Lung rupture was observed in two of the animals, and lung contusion and emphysema were seen in all animals treated with NPWT without the rigid disc. No injury to the heart or lungs was observed in the group of animals treated with NPWT using the rigid disc.
Conclusion
Inserting a rigid barrier between the heart and the sternum edges offers protection against heart rupture and lung injury during NPWT.
doi:10.1186/1749-8090-6-90
PMCID: PMC3142210  PMID: 21740574
7.  Macroscopic changes during negative pressure wound therapy of the open abdomen using conventional negative pressure wound therapy and NPWT with a protective disc over the intestines 
BMC Surgery  2011;11:10.
Background
Higher closure rates of the open abdomen have been reported with negative pressure wound therapy (NPWT) than with other wound management techniques. However, the method has occasionally been associated with increased development of fistulae. We have previously shown that NPWT induces ischemia in the underlying small intestines close to the vacuum source, and that a protective disc placed between the intestines and the vacuum source prevents the induction of ischemia. In the present study we compare macroscopic changes after 12, 24, and 48 hours, using conventional NPWT and NPWT with a protective disc between the intestines and the vacuum source.
Methods
Twelve pigs underwent midline incision. Six animals underwent conventional NPWT, while the other six pigs underwent NPWT with a protective disc inserted between the intestines and the vacuum source. Macroscopic changes were photographed and quantified after 12, 24, and 48 hours of NPWT.
Results
The surface of the small intestines was red and mottled as a result of petechial bleeding in the intestinal wall in all cases. After 12, 24 and 48 hours of NPWT, the area of petechial bleeding was significantly larger when using conventional NPWT than when using NPWT with the protective disc (9.7 ± 1.0 cm2 vs. 1.8 ± 0.2 cm2, p < 0.001, 12 hours), (14.5 ± 0.9 cm2 vs. 2.0 ± 0.2 cm2, 24 hours) (17.0 ± 0.7 cm2 vs. 2.5 ± 0.2 cm2 with the disc, p < 0.001, 48 hours)
Conclusions
The areas of petechial bleeding in the small intestinal wall were significantly larger following conventional NPWT after 12, 24 and 48 hours, than using NPWT with a protective disc between the intestines and the vacuum source. The protective disc protects the intestines, reducing the amount of petechial bleeding.
doi:10.1186/1471-2482-11-10
PMCID: PMC3095529  PMID: 21529362
negative pressure wound therapy; open abdomen; macroscopic changes; intestinal wall
8.  Sternum wound contraction and distension during negative pressure wound therapy when using a rigid disc to prevent heart and lung rupture 
Background
There are increasing reports of deaths and serious complications associated with the use of negative pressure wound therapy (NPWT), of which right ventricular heart rupture is the most devastating. The use of a rigid barrier has been suggested to offer protection against this lethal complication by preventing the heart from being drawn up against the sharp edges of the sternum. The aim of the present study was to determine whether a rigid barrier can be safely inserted over the heart with regard to the sternum wound edge movement.
Methods
Sternotomy wounds were created in eight pigs. The wounds were treated with NPWT at -40, -70, -120 and -170 mmHg in the presence and absence of a rigid barrier between the heart and the edges of the sternum. Wound contraction upon NPWT application, and wound distension under mechanical traction to draw apart the edges of the sternotomy were evaluated.
Results
Wound contraction resulting from NPWT was similar with and without the rigid barrier. When mechanical traction was applied to a NPWT treated sternum wound, the sternal edges were pulled apart. Wound distension upon traction was similar in the presence and absence of a the rigid barrier during NPWT.
Conclusions
A rigid barrier can safely be inserted between the heart and the edges of the sternum to protect the heart and lungs from rupture during NPWT. The sternum wound edge is stabilized equally well with as without the rigid barrier during NPWT.
doi:10.1186/1749-8090-6-42
PMCID: PMC3073896  PMID: 21450095
9.  Effects on heart pumping function when using foam and gauze for negative pressure wound therapy of sternotomy wounds 
Background
Negative pressure wound therapy (NPWT) has remarkable effects on the healing of poststernotomy mediastinitis. Foam is presently the material of choice for NPWT in this indication. There is now increasing interest in using gauze, as this has proven successful in the treatment of peripheral wounds. It is important to determine the effects of NPWT using gauze on heart pumping function before it can be used for deep sternotomy wounds. The aim was to examine the effects of NPWT when using gauze and foam on the heart pumping function during the treatment of a sternotomy wound.
Methods
Eight pigs underwent median sternotomy followed by NPWT at -40, -70, -120 and -160 mmHg, using foam or gauze. The heart frequency, cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, central venous pressure and left atrial pressure were recorded.
Results
Cardiac output was not affected by NPWT using gauze or foam. Heart frequency decreased during NPWT when using foam, but not gauze. Treatment with foam also lowered the central venous pressure and the left atrial pressure, while gauze had no such effects. Mean systemic arterial pressure, mean pulmonary artery pressure and systemic vascular resistance were not affected by NPWT. Similar haemodynamic effects were observed at all levels of negative pressure studied.
Conclusions
NPWT using foam results in decreased heart frequency and lower right and left atrial filling pressures. The use of gauze in NPWT did not affect the haemodynamic parameters studied. Gauze may thus provide an alternative to foam for NPWT of sternotomy wounds.
doi:10.1186/1749-8090-6-5
PMCID: PMC3031203  PMID: 21232105
10.  Wound contraction and macro-deformation during negative pressure therapy of sternotomy wounds 
Background
Negative pressure wound therapy (NPWT) is believed to initiate granulation tissue formation via macro-deformation of the wound edge. However, only few studies have been performed to evaluate this hypothesis. The present study was performed to investigate the effects of NPWT on wound contraction and wound edge tissue deformation.
Methods
Six pigs underwent median sternotomy followed by magnetic resonance imaging in the transverse plane through the thorax and sternotomy wound during NPWT at 0, -75, -125 and -175 mmHg. The lateral width of the wound and anterior-posterior thickness of the wound edge was measured in the images.
Results
The sternotomy wound decreased in size following NPWT. The lateral width of the wound, at the level of the sternum bone, decreased from 39 ± 7 mm to 30 ± 6 mm at -125 mmHg (p = 0.0027). The greatest decrease in wound width occurred when switching from 0 to -75 mmHg. The level of negative pressure did not affect wound contraction (sternum bone: 32 ± 6 mm at -75 mmHg and 29 ± 6 mm at -175 mmHg, p = 0.0897). The decrease in lateral wound width during NPWT was greater in subcutaneous tissue (14 ± 2 mm) than in sternum bone (9 ± 2 mm), resulting in a ratio of 1.7 ± 0.3 (p = 0.0423), suggesting macro-deformation of the tissue. The anterior-posterior thicknesses of the soft tissue, at 0.5 and 2.5 cm laterally from the wound edge, were not affected by negative pressure.
Conclusions
NPWT contracts the wound and causes macro-deformation of the wound edge tissue. This shearing force in the tissue and at the wound-foam interface may be one of the mechanisms by which negative pressure delivery promotes granulation tissue formation and wound healing.
doi:10.1186/1749-8090-5-75
PMCID: PMC2958889  PMID: 20920290
11.  Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways 
Background
Up-regulation of vascular endothelin type B (ETB) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, ex vivo, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ETB receptors in human internal mammary arteries.
Methods
Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using in vitro pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ETA and ETB receptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists.
Results
The endohtelin-1-induced contraction (after endothelin ETB receptor desensitization) and the endothelin ETA receptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ETB receptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 μM bisindolylmaleimide I and 10 μM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 μM SB203580, 10 μM PD98059 and 10 μM SP600125, respectively).
Conclusion
In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ETB receptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ETB receptor changes in cardiovascular disease.
doi:10.1186/1471-2261-8-21
PMCID: PMC2553399  PMID: 18778461
12.  A compare between myocardial topical negative pressure levels of -25 mmHg and -50 mmHg in a porcine model 
Background
Topical negative pressure (TNP), widely used in wound therapy, is known to stimulate wound edge blood flow, granulation tissue formation, angiogenesis, and revascularization. We have previously shown that application of a TNP of -50 mmHg to the myocardium significantly increases microvascular blood flow in the underlying tissue. We have also shown that a myocardial TNP levels between -75 mmHg and -150 mmHg do not induce microvascular blood flow changes in the underlying myocardium. The present study was designed to elucidate the difference between -25 mmHg and -50 mmHg TNP on microvascular flow in normal and ischemic myocardium.
Methods
Six pigs underwent median sternotomy. The microvascular blood flow in the myocardium was recorded before and after the application of TNP using laser Doppler flowmetry. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium), and after 20 minutes of LAD occlusion (ischemic myocardium).
Results
A TNP of -25 mmHg significantly increased microvascular blood flow in both normal (from 263.3 ± 62.8 PU before, to 380.0 ± 80.6 PU after TNP application, * p = 0.03) and ischemic myocardium (from 58.8 ± 17.7 PU before, to 85.8 ± 20.9 PU after TNP application, * p = 0.04). A TNP of -50 mmHg also significantly increased microvascular blood flow in both normal (from 174.2 ± 20.8 PU before, to 240.0 ± 34.4 PU after TNP application, * p = 0.02) and ischemic myocardium (from 44.5 ± 14.0 PU before, to 106.2 ± 26.6 PU after TNP application, ** p = 0.01).
Conclusion
Topical negative pressure of -25 mmHg and -50 mmHg both induced a significant increase in microvascular blood flow in normal and in ischemic myocardium. The increase in microvascular blood flow was larger when using -25 mmHg on normal myocardium, and was larger when using -50 mmHg on ischemic myocardium; however these differences were not statistically significant.
doi:10.1186/1471-2261-8-14
PMCID: PMC2467401  PMID: 18570679
13.  No hypoperfusion is produced in the epicardium during application of myocardial topical negative pressure in a porcine model 
Background
Topical negative pressure (TNP), commonly used in wound therapy, has been shown to increase blood flow and stimulate angiogenesis in skeletal muscle. We have previously shown that a myocardial TNP of -50 mmHg significantly increases microvascular blood flow in the myocardium. When TPN is used in wound therapy (on skeletal and subcutaneous tissue) a zone of relative hypoperfusion is seen close to the wound edge. Hypoperfusion induced by TNP is thought to depend on tissue density, distance from the negative pressure source, and the amount negative pressure applied. When applying TNP to the myocardium, a significant, long-standing zone of hypoperfusion could theoretically cause ischemia, and negative effects on the myocardium. The current study was designed to elucidate whether hypoperfusion was produced during myocardial TNP.
Methods
Six pigs underwent median sternotomy. Laser Doppler probes were inserted horizontally into the heart muscle in the LAD area, at depths of approximately, 1–2 mm. The microvascular blood flow was measured before and after the application of a TNP. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium) and after 20 minutes of LAD occlusion (ischemic myocardium).
Results
A TNP of -50 mmHg induced a significant increase in microvascular blood flow in normal myocardium (**p = 0.01), while -125 mmHg did not significantly alter the microvascular blood flow. In ischemic myocardium a TNP of -50 mmHg induced a significant increase in microvascular blood flow (*p = 0.04), while -125 mmHg did not significantly alter the microvascular blood flow.
Conclusion
No hypoperfusion could be observed in the epicardium in neither normal nor ischemic myocardium during myocardial TNP.
doi:10.1186/1749-8090-2-53
PMCID: PMC2217536  PMID: 18062803

Results 1-13 (13)