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Ann Thorac Surg 2005;79:1724-1730
© 2005 The Society of Thoracic Surgeons

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Original articles: General thoracic

Blood Flow Responses in the Peristernal Thoracic Wall During Vacuum-Assisted Closure Therapy

^a Department of Internal Medicine, Lund University Hospital, Lund, Sweden
^b Department of Cardiothoracic Surgery, Lund University Hospital, Lund, Sweden
^c Department of Cardiothoracic Anesthesia, Lund University Hospital, Lund, Sweden

Accepted for publication October 28, 2004.

^_* Address reprint requests to Ms Wackenfors, Experimental Vascular Research, BMC A13, SE-221 84 Lund, Sweden (E-mail: angelica.wackenfors{at}med.lu.se).

	Abstract

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
BACKGROUND: Vacuum-assisted closure (VAC) therapy is a recently introduced method for the treatment of poststernotomy mediastinitis. The aim of this study was to examine the effects of negative pressure on peristernal soft tissue blood flow and metabolism because the mechanisms by which vacuum-assisted closure therapy promotes wound healing are not known in detail.

METHODS: Microvascular blood flow was examined by laser Doppler velocimetry in an uninfected porcine sternotomy wound model. Microvascular blood flow was examined in the muscular and subcutaneous tissue, at different distances from the wound edge, after the application of –50 to –200 mm Hg. Wound fluid pH, partial pressures of oxygen and carbon dioxide, bicarbonate, and lactate were analyzed after 0, 30, and 60 minutes of continuous negative pressure.

RESULTS: Vacuum-assisted closure therapy induced an increase in the microvascular blood flow a few centimeters from the wound edge. In muscular tissue, the distance from the wound edge to the position at which the blood flow was increased was shorter than that in subcutaneous tissue. Close to the wound edge, relative hypoperfusion was observed. The hypoperfused zone was larger at high negative pressures and was especially prominent in subcutaneous tissue. Wound fluid partial pressure of oxygen and lactate levels were increased after 60 minutes of vacuum-assisted closure therapy, which may be the result of changes in the microvascular blood flow.

CONCLUSIONS: Vacuum-assisted closure therapy induces a change in microvascular blood flow that is dependent on the pressure applied, the distance from the wound edge, and the tissue type. It may be beneficial to tailor the negative pressure used for vacuum-assisted closure therapy according to the wound tissue composition. Wound fluid partial pressure of oxygen and lactate levels increased during vacuum-assisted closure therapy. This combination is known to promote wound healing.

	Introduction

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Mediastinitis is a devastating complication in open heart surgery. Vacuum-assisted closure (VAC) therapy is a recently introduced technique that promotes the healing of difficult wounds, including poststernotomy mediastinitis [1]. The technique entails application of a negative pressure to a sealed, airtight wound. The suction force created by VAC therapy enables the drainage of excessive fluid and debris, which leads to the removal of wound edema, reduction in bacterial counts, enhanced blood flow, and granulation tissue formation [1–4].

The physiologic, cellular, and molecular mechanisms by which VAC therapy accelerates wound healing are still not known in detail. Tissue perfusion and oxygenation are crucial to ensure healing [5]. The two most important risk factors for developing a deep sternal wound infection are diabetes and the use of internal thoracic arteries as bypass grafts [6, 7], both of which are believed to decrease the peristernal soft tissue blood perfusion. Laser Doppler velocimetry measurements have shown that VAC induces an increase in blood flow to a wound on the back of pigs [4]. Enhancing blood flow to the soft tissue of the peristernal wound may be one of the mechanisms by which VAC therapy facilitates sternal wound healing. To evaluate this hypothesis, the microvascular blood flow was studied by laser Doppler velocimetry in a porcine sternotomy wound model.

Previous observations show that microvascular blood flow to a wound on the back of pigs increases four times above baseline value when a negative pressure of 125 mm Hg is applied, whereas it is inhibited at negative pressures of 400 mm Hg and above [4]. Even though the tissue type and distance from the wound edge were not considered in the above-mentioned study, a negative pressure of 125 mm Hg was selected for subsequent experiments and is currently the pressure of choice for the clinical treatment of poststernotomy mediastinitis. In the present study, the microvascular blood flow was examined in detail using different negative pressures (–50 to –200 mm Hg) in an uninfected porcine sternotomy wound model. Subcutaneous and muscular tissues were studied separately, and the blood flow was measured at different distances from the sternal wound edge. The aim was to determine the optimal negative pressure for stimulating peristernal microvascular blood flow and for the treatment of deep sternal wounds. Wound fluid was trapped in the VAC tubing and analyzed with regard to pH, partial pressures of oxygen (PO₂) and carbon dioxide (PCO₂), bicarbonate, and lactate to evaluate the metabolic effects of altered microvascular blood flow during VAC therapy.

	Material and Methods

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Animals
An uninfected porcine sternotomy wound model was use for the present study. Nineteen domestic Landrace pigs of both sexes, with a mean body weight of 70 kg, were fasted overnight with free access to water. The study was approved by the Ethics Committee for Animal Research, Lund University, Sweden, which conforms to the principles outlined in the Declaration of Helsinki. All the animals received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" as promulgated by the Council of the American Physiologic Society and published by the National Institutes of Health (1985).

Anesthesia and Surgical Procedure
Ketamine was used for premedication. Anesthesia was induced by intravenous sodium thiopental and maintained by continuous infusion of pentobarbital and fentanyl. Pancuronium was given intravenously to achieve muscle paralysis. The pigs were surgically prepared for VAC therapy. A midline sternotomy was performed, and the pericardium was opened. A polyurethane foam dressing was placed between the sternal edges. Two noncollapsible drainage tubes were inserted into the foam. The open wound was sealed with a transparent adhesive drape. The drainage tubes were connected to a purpose-built vacuum source (VAC pump unit; KCI, Copenhagen, Denmark), which delivered a continuous negative pressure of –50, –75, –100, –125, –150, –175, or –200 mm Hg. For details, see the study by Sjögren and colleagues [8], in which identical settings were used. For a schematic illustration, see Figure 1.

View larger version (56K): [in this window] [in a new window]   Fig 1. A schematic illustration of the experimental setup showing a cross-section of the open wound with the vacuum-assisted closure (VAC) pump unit to the right and the laser Doppler velocimetry equipment to the left. A polyurethane foam dressing was placed between the sternal edges. Two noncollapsible drainage tubes were inserted into the foam. The open wound was sealed with a transparent adhesive drape. The drainage tubes were connected to a purpose-built vacuum source (vacuum-assisted closure pump unit), which delivered a continuous negative pressure. A canister in the pump unit collected exudates from the wound. Microvascular blood flow was measured by laser Doppler velocimetry. Filament probes (0.5 mm) were inserted into subcutaneous or the deep muscular tissue of the wound edge, and recordings were made with three parallel probes. A skin probe was placed 10 cm from the wound. Wound fluid from the vacuum-assisted closure–treated pigs was sampled from the vacuum-assisted closure drainage tube, close to the wound edge.

Blood and Wound Fluid Samples
Twelve pigs underwent the surgical procedure described above. Six pigs were treated with VAC therapy of –75 mm Hg, and another 6 were used as controls termed "sham therapy." Arterial blood was sampled from the right carotid artery, and venous blood was sampled from the right external jugular vein. Wound fluid from the VAC-treated pigs was sampled from the drainage tube, close to the wound edge. Wound fluid from the sham-treated pigs was drawn from a tube that was inserted into the substernal cavity in the upper part of the sternotomy wound, not in contact with the heart. Wound fluid and arterial and venous blood PO₂, PCO₂, bicarbonate, pH, and lactate were analyzed (ABL 725; Radiometer Copenhagen, Brönshöj, Denmark) immediately before (0 minutes) and after 30 and 60 minutes of VAC therapy.

Calculations and Statistics
The laser Doppler experiments were performed on 7 pigs, and the blood and wound fluid was sampled from 6 VAC-treated and 6 sham-treated pigs. Calculations and statistical analysis were performed using GraphPad 4.0 software (GraphPad Software Inc, San Diego, CA). Statistical significance was defined as p less than 0.05, using the Mann-Whitney test when comparing two groups and the Kruskal-Wallis test with Dunnett's post hoc test when comparing three groups or more. All differences referred to in the text have been statistically verified. Values are presented as mean ± standard error of the mean.

	Results

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Vacuum-assisted closure therapy induced an increase in the peristernal soft tissue and muscle tissue blood flow (Figs 2A, 3A). In muscular tissue, the distance from the wound edge to the peak blood flow change was shorter (2.5 cm, at –125 mm Hg; Fig 4) than in subcutaneous tissue (3.5 cm, at –125 mm Hg; Fig 4). The blood flow increased with increasing subatmospheric pressure in both subcutaneous and muscular tissue (Fig 4). In subcutaneous tissue, the flow increase at –50 mm Hg was 15% ± 10%, whereas it was 121% ± 28% at –150 mm Hg (3.5 cm from the edge; p < 0.05; Fig 4). In muscular tissue, the flow increase at –50 mm Hg was 26% ± 23%, whereas it was 189% ± 56% at –100 mm Hg (2.5 cm from the edge; p < 0.05; Fig 4).

View larger version (36K): [in this window] [in a new window]   Fig 2. Representative example of microvascular blood flow changes after application of vacuum-assisted closure therapy (–125 mm Hg) in subcutaneous tissue at 3.0 cm (A), 0.5 cm (B), and 4.5 cm (C) from the sternal wound edge.

View larger version (40K): [in this window] [in a new window]   Fig 3. Representative example of microvascular blood flow changes after application of vacuum-assisted closure therapy (–125 mm Hg) in muscular tissue at 2.0 cm (A), 0.5 cm (B), and 4.5 cm (C) from the sternal wound edge.

View larger version (36K): [in this window] [in a new window]   Fig 4. Microvascular blood flow in subcutaneous () and muscular tissue (), at increasing distance from the sternal wound edge in 6 domestic pigs after application of subatmospheric pressures of –50 to –200 mm Hg. Changes in blood flow were calculated as percent of baseline flow and are presented as mean ± standard error of the mean.

Adenosine triphosphate (0.5 mg/kg) was administered intravenously at the end of the experiment as a positive control, and microvascular blood flow was recorded with a probe on the skin and in subcutaneous and muscular tissue. Adenosine triphosphate first induced a decrease in blood flow (–60% ± 6% in the skin, –59% ± 8% in the subcutaneous tissue, and –76% ± 15% in the muscular tissue), followed by an increase in blood flow (79% ± 32% in the skin, 105% ± 23% in the subcutaneous tissue, and 85% ± 19% in the muscular tissue), indicating functioning probes and equipment. The basal blood flow was 15 ± 3 perfusion units in the skin, 76 ± 4 perfusion units in the subcutaneous tissue, and 66 ± 4 perfusion units in the muscular tissue. A skin probe, 10 cm from the wound edge, was used as a negative control to monitor microvascular blood circulation continuously during the experiment. The skin blood flow was not affected by VAC therapy, indicating that the changes in blood flow were localized to the wound and no systemic effects contributed.

Wound fluid PO₂ was increased and PCO₂ was decreased after 60 minutes of VAC therapy, whereas they remained unchanged during sham therapy (Table 1). Wound fluid lactate was increased after 30 and 60 minutes of VAC therapy, and was unchanged during sham therapy (Table 1). Wound fluid pH and bicarbonate were not altered by VAC or sham therapy (Table 1). No changes were observed in systemic arterial or venous blood pH, bicarbonate, PO₂, PCO₂, or lactate during VAC therapy (Table 1), indicating that the alteration seen in the wound fluid was the result of local effects.

	Comment

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

Vacuum-assisted closure therapy induced an increase in the peristernal soft tissue blood flow. The change in blood flow is probably related to local effects because the blood flow was not affected by the negative pressure at a distance of 4.5 cm from the wound edge. The blood flow increased with elevated subatmospheric pressure in both subcutaneous and muscular tissue. When the area under the flow-distance curve was analyzed, covering 0.5 to 4.5 cm from the wound edge, a maximal net increase in blood flow was observed at –75 and –100 mm Hg, in muscular tissue. There is a discrepancy between the present results and previous data that show a peak increase in wound edge blood flow at –125 mm Hg [4]. One explanation of this discrepancy may be that the former study was performed on a wound on the pigs' back, whereas the present study is performed on a sternotomy wound. The differences in wound tissue composition may alter the effects of negative pressure on blood flow. Furthermore, in the present study, the blood flow was analyzed in detail 0.5 to 4.5 cm from the wound edge at 1-cm increments, whereas no specific distances were analyzed in the study by Morykwas and associates [4]. Vacuum-assisted closure therapy has been shown to be advantageous in infected or nonhealing chronic wounds, but not in acutely injured wounds [12]. An infected wound is often edematous and perfusion is decreased, leading to decreased nutrition of the wound margins. Vacuum-assisted closure therapy decreases wound edema [2] and improves blood flow, as shown in the present study. The effects of VAC therapy may therefore be even more pronounced in an infected wound than in this experimental setup using a noninfected acute sternotomy wound.

Interestingly, a difference in the profiles of the blood flow responses could be observed between the subcutaneous and the muscular tissue. In muscular tissue, the distance from the wound edge to the point at which the blood flow increased was shorter than in subcutaneous tissue. Pressure may be transduced differently in a soft and in a dense tissue, and a less dense tissue collapses more easily when affected by pressure. Thus, the effect of VAC therapy may vary according to the wound tissue composition. Currently, the pressure in the tubing guides the VAC therapy. We suggest that the pressure transduction in the tissue is of greater importance. To obtain similar therapeutic effects of VAC therapy in different wounds, it may be beneficial to tailor the negative pressure according to wound tissue composition.

This study shows that the changes in the peristernal wound blood flow caused by VAC therapy vary with the distance from the wound edge. A few centimeters away from the wound edge, the blood flow increases when subatmospheric pressure is applied. Conversely, in immediate proximity to the wound, the negative pressure induces relative hypoperfusion. Pressure against the wound wall may be beneficial during surgical procedures because it has been shown to tamponade superficial bleeding [13]. On the other hand, long-standing hypoperfusion may cause ischemia. To balance these effects, a negative pressure that does not cause a large ischemic zone, but still eliminates interstitial fluid accumulation and bleeding, may be preferable. In muscular tissue, the hypoperfused zone is smaller than in the subcutaneous tissue, which may be attributable to the easier collapse of soft tissue during pressure. The size of the hypoperfused zone depends on the subatmospheric pressure applied, and increases with increasing pressure.

To evaluate the nutritive effects of the blood flow changes in the uninfected sternotomy wound edge, pH, PO₂, PCO₂, bicarbonate, and lactate were analyzed in the wound fluid at –75 mm Hg. This pressure was chosen on the basis of the blood flow studies, in which –75 mm Hg produced a high net increase in blood flow and a small zone of relative hypoperfusion. When analyzing wound fluid factors, it was found that PO₂ increased during VAC therapy at –75 mm Hg. This increase in oxygen supply to the peristernal wound edges may well have been the result of the change in microvascular blood flow demonstrated by the laser Doppler experiments. Blood perfusion and oxygenation are crucial to ensure healing [5]. Already in 1969, Hunt and coworkers [14] suggested that oxygen was required for the oxidation of metabolic substrates by inflammatory cells present in the wound environment. Oxygen is an essential cofactor in collagen synthesis, and participates in the regulation of cell proliferation [14]. Oxygen is also important in the defense against infections [15]. This may be one of the mechanisms by which the wound repair process is facilitated by VAC therapy.

Wound fluid lactate was increased during VAC therapy. One explanation of this increase may be the relative hypoperfusion that is created by the subatmospheric pressure in the immediate proximity of the wound edge. However, it has been shown that hypoxia only marginally increases wound lactate [16], and ischemia produces an acidotic local wound effluent [17], which was not observed in our study. More important sources of lactate are neutrophils, macrophages and fibroblasts, and other proliferating cells that are present in the granulation tissue of wounds [18–20]. These cells produce large amounts of lactate through aerobic glycolysis [21]. Interestingly, our results showed that both PO₂ and lactate increased in the wound fluid during VAC therapy. It has been shown that elevated lactate levels often are accompanied by increased oxygen tension, and this combination appears to promote healing of wounds [16, 22, 23]. Lactate stimulates wound granulation tissue formation by inducing collagen transcription and vascular endothelial growth factor production, whereas increased PO₂ promotes collagen deposition and angiogenesis [24–26]. The increases in wound fluid PO₂ and lactate observed in the present experiments may initiate the granulation tissue formation that has been demonstrated during VAC therapy [4]. Because of the high pressure gradient across the tissue in the close proximity of the VAC wound edge, this zone may be perfused by diffusion. This theory is supported by the high PO₂ levels without acidosis in the wound fluid and the fact that no development of necrosis is observed clinically during VAC therapy. The wound fluid variables were analyzed at –75 mm Hg, and the effects at –125 mm Hg therefore cannot be deduced from the present study. It may be assumed that –125 mm Hg induces similar changes in PO₂ and lactate concentrations because the blood flow to the wound edge increases also at –125 mm Hg, although to a lesser extent.

A common practice in thoracic surgery is unilateral or bilateral harvesting of the internal mammary arteries. Postoperative mediastinitis is more common when bilateral harvesting has been performed, especially in patients with diabetes and obesity [6, 12, 27]. The reason for the high risk of infection in these groups of patients may be that the soft tissue is poorly perfused postoperatively. The blood flow and the subsequent nutrition of the wound edge may then not be sufficient for healing. Stimulating blood flow to the sternotomy wound edge in patients with diabetes or when bilateral harvesting has been conducted may be crucial to ensure healing. Further studies aimed at optimizing sternotomy wound edge blood flow may lead to the development of safe techniques for wound closure in patients at high risk of postoperative mediastinitis, eg, performing delayed subcutaneous closure after a brief period of VAC therapy.

In conclusion, VAC therapy elicits an increase in microvascular blood flow a few centimeters from the wound edge. The peak increase in blood flow occurred closer to the wound edge in muscular than in subcutaneous tissue. In the immediate proximity of the wound edge, a zone of relative hypoperfusion was observed. This zone was larger at high negative pressures and was especially prominent in subcutaneous tissue. It may be concluded that the vacuum pressure is transduced differently in soft and dense tissue. Therefore, it may be beneficial to tailor the VAC negative pressure according to the wound tissue composition. A negative pressure of 75 or 100 mm Hg may be profitable because it effectively stimulates peristernal soft tissue blood flow without producing a large zone of relative hypoperfusion. Wound fluid PO₂ was increased and PCO₂ decreased after 60 minutes of VAC therapy, which may be a result of the changes in blood flow. Furthermore, lactate levels were increased, which may be related to inflammation and rapid cell growth during granulation tissue formation. The combination of increased PO₂ and lactate levels in the wound environment has previously been reported to promote wound healing [16, 22, 23], and may in part explain the mechanisms by which VAC therapy accelerates wound healing.

	Acknowledgments

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
This study was supported by the Swedish Hypertension Society, the Swedish Medical Association, the Royal Physiographic Society (Lund), the Swedish Medical Research Council, the Medical Society in Lund, the Crafoord Foundation, the Swedish Heart-Lung Foundation, and the Swedish Government Grant for Clinical Research.

	References

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

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