Ronny Gustafsson

Effects of vacuum‐assisted closure therapy on inguinal wound edge microvascular blood flow

Vacuum‐assisted closure (VAC) therapy has been shown to facilitate wound healing. Data on the mechanisms are scarce, although beneficial effects on blood flow and granulation tissue formation have been presented. In the current study, laser Doppler was used to measure microvascular blood flow to an inguinal wound in pigs during VAC therapy (− 50 to − 200 mmHg), including consideration of the different tissue types and the distance from the wound edge. VAC treatment induced an increase in microvascular blood flow a few centimeters from the wound edge. The increase in blood flow occurred closer to the wound edge in muscular as compared to subcutaneous tissue (1.5 cm and 3 cm, at − 75 mmHg). In the immediate proximity to the wound edge, blood flow was decreased. This hypoperfused zone was increased with decreasing pressure and was especially prominent in subcutaneous as compared to muscular tissue (0–1.9 cm vs. 0–1.0 cm, at − 100 mmHg). When VAC therapy was terminated, blood flow increased multifold, which may be due to reactive hyperemia. In conclusion, VAC therapy affects microvascular blood flow to the wound edge and may thereby promote wound healing. A low negative pressure during treatment may be beneficial, especially in soft tissue, to minimize possible ischemic effects. Intermittent VAC therapy may further increase blood flow.

Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo.

BACKGROUND A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. A method to evaluate and recondition lungs ex vivo has been tested on donor lungs that have been rejected for transplantation. METHODS The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation (ECMO) circuit with STEEN solution (Vitrolife AB, Kungsbacka, Sweden) mixed with erythrocytes. The hyperoncotic solution dehydrates edematous lung tissue. Functional evaluations were performed with deoxygenated perfusate by varying the inspired fraction of oxygen. After the reconditioning, the lungs were kept immersed at 8 degrees C in extracorporeal membrane oxygenation until transplantation was performed. RESULTS Six of nine initially rejected donor lungs were reconditioned to acceptable function, and in six recipients, double lung transplantation was performed. Three-month survival was 100%. One patient has since died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are alive and well without any sign of bronchiolitis obliterans syndrome 24 months after the transplantation. CONCLUSIONS The result from the present study is promising, and we continue to transplant reconditioned lungs.

ADP Receptor P2Y12 Is Expressed in Vascular Smooth Muscle Cells and Stimulates Contraction in Human Blood Vessels

Objective—ADP plays an important role in platelet aggregation by activating P2Y12 receptors. We assessed the hypothesis that P2Y12 receptors are expressed in vascular smooth muscle cells (VSMC). Methods and Results—P2Y12 receptor mRNA was found to have a high expression among the P2 receptors in human VSMC, significantly higher than the other 2 ADP receptors (P2Y1 and P2Y13, real-time polymerase chain reaction). Western blots gave a band of 50 kD, similar to that in platelets. To unmask a P2Y12 receptor-mediated vasoconstriction by simulating the in vivo situation, vessels were precontracted to a submaximal level. 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small veins (Emax=15±6% of 60mmol/L K+ contraction, pEC50=5.6±0.6, Emax=21±1%, pEC50=6.8±0.1, and Emax=48±9%, pEC50=6.6±0.4). The selective P2Y12 antagonist AR-C67085 blocked 2-MeSADP contractions. The contraction was not reduced in patients using clopidogrel, a drug inhibiting ADP-induced platelet aggregation by blocking the P2Y12 receptor. This may be explained by the high instability of the active clopidogrel metabolite that never reaches the systemic circulation. Conclusion—ADP acting on P2Y12 receptors not only is important for platelet activation but also stimulates vasoconstriction. Stable drugs with antagonistic effects on P2Y12 receptors, affecting both platelets and VSMC, could be of double therapeutic benefit in their prevention of both thrombosis and vasospasm.

Deep sternal wound infection: a sternal-sparing technique with vacuum-assisted closure therapy.

BACKGROUND Vacuum-assisted closure therapy is a novel treatment employed to aid wound healing in different areas of the body and recently also in sternotomy wounds. Aggressive vacuum-assisted closure treatment of the sternum in postoperative deep wound infection enhances sternal preservation and the rate of possible rewiring. METHODS The records of 40 consecutive patients with deep sternal wound infection were reviewed. Sternal bone sparing was achieved by using layers of paraffin gauze (Jelonet; Smith and Nephew Medical, Hull, UK) at the bottom of the wound in order to cover and protect visible parts of the right ventricle, lung tissue, and grafts from the sternal edges. Two separate layers of polyurethane foam (KCI, Copenhagen, Denmark) were placed so as to fit between the sternal edges and subcutaneously. A continuous negative pressure of 125 mm Hg was applied and subsequent revision was made exclusively in nongranulation areas. RESULTS There were no deaths during the 90 days of follow-up. Three late deaths unrelated to the infection and three subcutaneous fistulas occurred during the total follow-up period (3 to 41 months). The median duration of the vacuum-assisted closure therapy was 10 days (range, 3 to 34). The series represents a total of 474 days with the vacuum-assisted closure device without serious adverse events. CONCLUSIONS In our opinion this modified vacuum-assisted closure therapy is a safe and reproducible option to bridge patients with postoperative deep sternal wound infection to complete healing. Reconstruction of the sternum was achieved in all patients without the use of muscle or omental flap surgery.

Topical negative pressure wound therapy: a review of its role and guidelines for its use in the management of acute wounds

Over the past two decades, topical negative pressure (TNP) wound therapy has gained wide acceptance as a genuine strategy in the treatment algorithm for a wide variety of acute and chronic wounds. Although extensive experimental and clinical evidence exists to support its use and despite the recent emergence of randomised control trials, its role and indications have yet to be fully determined. This article provides a qualitative overview of the published literature appertaining to the use of TNP therapy in the management of acute wounds by an international panel of experts using standard methods of appraisal. Particular focus is applied to the use of TNP for the open abdomen, sternal wounds, lower limb trauma, burns and tissue coverage with grafts and dermal substitutes. We provide evidence‐based recommendations for indications and techniques in TNP wound therapy and, where studies are insufficient, consensus on best practice.

HeartMate II left ventricular assist device; early European experience

OBJECTIVE The novel axial flow left ventricular assist device HeartMate II was introduced into clinical practice in Europe as part of the pilot study and after CE approval in November 2005. In order to get an overview of the use and performance of the device in Europe a group of investigators was founded to compare the initial results. METHODS In a retrospective analysis of the first 101 consecutive cases in Europe, data were collected with regard to postoperative outcome and severe adverse events and anticoagulation protocols. Results were stratified by intention to treat as a bridge to transplant or as chronic support therapy in heart failure (destination therapy). RESULTS In 70% of patients, the HeartMate II was intended as a bridge to transplant therapy, in 30%, it was used as a destination therapy device. The perioperative mortality post implant was 20% in the bridge to transplant patients and 7% in the destination therapy arm. However, after 1 year a comparable survival was observed in both groups (69% destination therapy, 63% bridge to transplant). Main causes of death were multiple organ failure (n=12) and cerebrovascular accidents (n=5). All, but one cerebrovascular accident occurred in the first 9 days after surgery. Only one other death was reported thereafter and there was no mechanical failure of the device. CONCLUSIONS Even in the early experience the HeartMate II was used as a chronic support device in a substantial number of patients in Europe. Although the total experience is still limited, the incidence of cerebrovascular accidents is very low and the survival beyond the perioperative period is excellent.

Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor.

The present study was aimed at examining P2 receptor‐mediated vasodilatation in human vessels. The isometric tension was recorded in isolated segments of the human left internal mammary artery branches precontracted with 1 μM noradrenaline. Endothelial denudation abolished the dilator responses. The selective P2Y1 agonist, 2‐MeSADP, induced a potent vasodilatation (pEC50=6.9±0.1). The P2Y1 antagonist of 10 μM, MRS 2216, shifted the 2‐MeSADP concentration‐response curve 1.1 log units to the right. The combined P2Y1 and P2X agonist, 2‐MeSATP, stimulated a dilatation with a potency similar to that of 2‐MeSADP. Furthermore, MRS 2216 had a similar antagonistic effect on both 2‐MeSATP and 2‐MeSADP indicating that P2X receptors do not mediate vasodilatation. Both the P2Y2/4 agonist, UTPγS and the P2Y6 agonist, UDPβS, stimulated potent dilatations (pEC50=7.8±0.4 for UTPγS and 8.4±0.2 for UDPβS). The 2‐MeSADP‐induced nitric oxide (NO)‐mediated dilatation was studied in the presence of 10 μM indomethacin, 50 nM charybdotoxin and 1 μM apamin. The involvement of the endothelium‐derived hyperpolarising factor (EDHF) was investigated in the presence of 0.1 mM L‐NOARG and indomethacin. The involvement of prostaglandins was investigated in the presence of L‐NOARG, charybdotoxin and apamin. Both NO, EDHF and prostaglandins mediated 2‐MeSADP dilatation with similar efficacy (Emax=25±5% for NO, 25±6% for EDHF and 27±5% for prostaglandins). In conclusion, extracellular nucleotides induce endothelium‐derived vasodilatation in human vessels by stimulating P2Y1, P2Y2/4 and P2Y6 receptors, while P2X receptors are not involved. Endothelial P2Y receptors mediate dilatation by release of EDHF, NO and prostaglandins

Comparative outcome of double lung transplantation using conventional donor lungs and non-acceptable donor lungs reconditioned ex vivo

A method to evaluate and recondition lungs ex vivo has been tested on donor lungs that have been rejected for transplantation. In the present paper, we compare early postoperative course between the six patients who received reconditioned lungs and the patients who received conventional donor lungs during the same period of time. During 2006 and 2007, a total of 21 patients underwent double sequential lung transplantation at the University Hospital of Lund. Six of those patients received reconditioned lungs. The other 15 patients received conventional donor lungs for transplantation without reconditioning ex vivo. The results are presented as median and interquartile range. Time in intensive care unit (days) between recipients of reconditioned lungs [13 (5-24) days], and recipients of conventional donor lungs [7 (5-12) days], P=0.44. Total hospital stay after transplantation (days) between recipients of reconditioned lungs [52 (47-60) days] and recipients of conventional donor lungs [44 (37-48) days], P=0.9. Ex vivo lung evaluation and reconditioning might not prolong early postoperative course in double lung transplantation. However, given the small number of patients, there might be a failure to detect a difference between the two groups.

The effect of vacuum-assisted closure therapy on the pig femoral artery vasomotor responses.

Vacuum‐assisted closure (VAC) is frequently used to treat wound infections. The aim of the present study was to evaluate the effect of VAC therapy on blood vessels. Vasodilatation and vasoconstriction were studied in isolated ring segments of the pig femoral artery after continuous VAC therapy of an inguinal wound for 12 hours. Vasoconstriction induced by endothelin‐1 (ET‐1), which is mainly an endothelin type A receptor agonist (Emax = 181 ± 2% of potassium), and the endothelin type B receptor agonist, sarafotoxin 6c (Emax = 30 ± 1%), were significantly increased after VAC therapy (ET‐1; 325 ± 3% and sarafotoxin 6c; 69 ± 1%). The norepinephrine‐, phenylephrine‐, and angiotensin II‐induced vasoconstrictions were not affected by VAC therapy. Acetylcholine induced an endothelium‐dependent dilatation that was enhanced after VAC therapy (Rmax = 38 ± 1% of norepinephrine‐preconstriction after sham and 47 ± 1% after VAC therapy, p < 0.05). The dilatory response was mediated by nitric oxide (Rmax = 39 ± 1%), prostaglandins (5 ± 1%) and endothelium‐derived hyperpolarizing factor (16 ± 1%), which were all significantly increased after VAC therapy. In conclusion, VAC therapy for 12  hours enhances an endothelin type A and type B receptor‐mediated vasoconstriction. This may be compensated for by a more efficacious endothelium‐dependent vasodilatation. No spontaneous bleeding, perforation, dissection, or other macroscopic change could be observed in the arteries exposed to VAC therapy.

The cost of vacuum-assisted closure therapy in treatment of deep sternal wound infection.

Objectives. Surgical sites infections are very expensive and the total costs for coronary artery bypass grafting (CABG) surgery followed by deep sternal wound infection (DSWI) with conventional therapy are estimated to be 2.8 times that for normal, CABG surgery. Promising results have been reported with vacuum-assisted closure (VAC) therapy in patients with DSWI. This study presents the cost of VAC therapy in patients with DSWI after CABG surgery. Design. Thirty-eight CABG patients with DSWI, between 2001 and 2005, were treated with VAC therapy. The cost of surgery, intensive care, ward care, laboratory tests and other costs were analyzed. Results. No three-month mortality or recurrent infection was observed. The average cost of CABG procedure and treatment of DSWI was 2.5 times higher than the mean cost of CABG alone. No significant correlations were found between the preoperative EuroSCORE and the cost of DSWI therapy. Conclusions. VAC therapy for patients who underwent CABG surgery followed by DSWI seems to be cost effective, and has low mortality rate.