Negative pressure wound therapy: a systematic review on effectiveness and safety.

OBJECTIVES: We reviewed the use of negative pressure wound treatment (NPWT) for problematic wounds. METHODS: A systematic literature review was undertaken to assess the effectiveness and safety of NPWT. Randomized controlled trials (RCTs) assessing NPWT were included. RESULTS: A total of 14 RCTs were included. Trials included patients with pressure wounds (2), post-traumatic wounds (3), diabetic foot ulcers (4) and miscellaneous chronic ulcers (5). In all trials NPWT was at least as effective and in some cases more effective than the control treatment. Most evidence supports the effectiveness of NPWT on chronic leg ulcers and posttraumatic ulcers. NPWT appears to be a safe treatment, and serious adverse events have been rarely reported. Only two trials were classified as high quality studies, whereas the remaining were classified as having poor internal validity. CONCLUSIONS: Reliable evidence on the effectiveness of NPWT is scarce. Tentative evidence indicates that the effectiveness of NPWT is at least as good as or better than current local treatment for wounds. The need for large high-quality randomised studies is apparent.

Revascularization decreases 8-isoprostaglandin F2alpha excretion in chronic lower limb ischemia.

8-Isoprostaglandin F2alpha is one of a series of isoprostanes formed by free radical catalysed peroxidation of arachidonic acid. Urinary 8-isoprostaglandin F2alpha is a new marker which reflects oxidative stress in vivo and can be utilized as a diagnostic tool to assess the extent of oxidative stress in various disease states associated with lipid peroxidation. Increased levels of 8-isoprostaglandin F2alpha in cardiac ischemia/reperfusion provide evidence for oxidative stress during coronary perfusion. In animal studies, the restoration of blood flow after lower limb ischemia is followed by reperfusion syndrome. In this study we investigated whether lower limb ischemia/reperfusion is associated with oxidative stress, as reflected by urinary levels of 8-isoprostaglandin F2alpha. Ten patients (mean age 72 years, range 61-82 years) suffering from chronic lower limb ischemia and 10 healthy volunteers (mean age 69 years, range 60-79 years) participated in the study. In all patients, diagnostic angiography had revealed stenosis or occlusion either in the aortoiliac or femoropopliteal region. Surgical revascularization consisted of femoropopliteal reconstruction, femorofemoral reconstruction, aortobifemorial reconstruction, or femoral endartectomy. Urine samples from patients were collected a day before surgery and in the second postoperative day. Urinary 8-isoprostaglandin F2alpha was extracted on a C2 silica cartridge and determinated by radioimmunoassay. After revascularization, 8-isoprostaglandin F2alpha excretion (pg/micromol creatinine, mean +/- SD) was decreased by 2.5-fold (preoperative 48.9 +/- 8.9, postoperative 19.1 +/- 9.5, P < 0.001). The postoperative values were similar to the concentrations measured in healthy volunteers (18.0 +/- 11.0). All revascularizations were successful, and the increase in ankle-brachial index (preoperative 0-0.6, postoperative 0.4-0.8) revealed improved blood flow in the ischemic lower limb. We suggest that, as assessed by the quantitation of urinary 8-isoprostaglandin F2alpha, chronic lower limb ischemia is associated with increased oxidative stress, which is decreased by revascularization.

Inflammatory cytokines and soluble receptors after coronary artery bypass grafting.

Much interest has been focused on the overexpression of proinflammatory cytokines, but studies on their soluble receptors are rare. For a comprehensive picture of cytokine activation in cardiac surgery, a combination of cytokines and the corresponding soluble receptor concentration should be determined. Blood samples were collected from the radial artery and coronary sinus perioperatively in ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. TNF-alpha, IL-6, sTNFRI, sTNFRII, and sIL-6R levels in the plasma were determined. Systemic TNFRI, TNFRII and IL-6 increased significantly after reperfusion to the myocardium, while perioperative systemic sIL-6r levels were similar. Arterial and sinus levels of TNFRI, TNFRII and sIL-6r were similar before cardiopulmonary bypass. Five minutes after reperfusion to the myocardium, higher sinus TNFRI and TNFRII and lower sinus sIL-6R levels were observed as compared to the arterial levels. The myocardium release of sTNFRI (r=0.57, P=0.089) and sTNFRII (r=0.64, P=0.047) positively correlated with the change of cardiac index after cardiopulmonary bypass. Myocardium releases sTNFRI and sTNFRII after ischaemic-reperfusion injury, and this may be of benefit to cardiac performance. sIL-6R is constantly being produced in areas other than the myocardium, while sIL-6R levels are reduced by consumption in the myocardium after ischaemic-reperfusion injury.

Cardioprotective effect of adenosine pretreatment in coronary artery bypass grafting.

OBJECTIVE: There are several reports of the use of adenosine as a cardioprotective agent during cardiac surgery. Adenosine treatment might affect neutrophils and inflammatory mediators. The present prospective randomized study was designed to investigate the effect of adenosine pretreatment on myocardial recovery and inflammatory response in patients undergoing elective coronary artery bypass surgery. DESIGN: A prospective, randomized, controlled study. SETTING: Operative unit and ICU in a university hospital in Finland. PATIENTS: Thirty male patients undergoing primary, elective coronary revascularization. INTERVENTIONS: Patients in the adenosine group received a 7-min infusion of adenosine (total, 650 microg/kg) before the initiation of cardiopulmonary bypass. MEASUREMENTS: Postoperative creatine kinase (CK)-MB release and hemodynamics were recorded. Perioperative leukocyte and cytokine release were measured. RESULTS: Adenosine pretreatment resulted in less CK-MB release and an improved postbypass cardiac index. Similar leukocyte counts and cytokine responses were seen in both groups perioperatively. Neutrophil counts were similar between the groups before and after myocardial ischemia when measured simultaneously in arterial and coronary sinus blood. CONCLUSIONS: The present results support the hypothesis that adenosine pretreatment is cardioprotective in humans, but the present dose failed to regulate the inflammatory responses after coronary artery bypass grafting.

Anti-inflammatory effects of 17beta-estradiol pretreatment in men after coronary artery surgery.

OBJECTIVE: To investigate the anti-inflammatory and hemodynamic effects of 17beta-estradiol in men undergoing elective coronary artery bypass graft surgery (CABG). DESIGN: Prospective, randomized, controlled. SETTING: Operating room and intensive care unit in a university hospital. PARTICIPANTS: Twenty-one men undergoing primary, elective CABG surgery. INTERVENTION: 17beta-estradiol, 2mg, was given orally twice in 14 hours before the operation. MEASUREMENTS AND MAIN RESULTS: Leukocyte counts, plasma myeloperoxidase, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 were measured perioperatively. Leukocyte counts were lower in the 17beta-estradiol group than in controls at 6 hours (11.4 +/- 2.0 hours v 15.5 +/- 4.7 hours x 10(9)/L) and 20 hours (11.6 +/- 1.9 hours v 13.6 +/- 2.5 hours x 10(9)/L) after reperfusion (p = 0.03). The release of myeloperoxidase was lower in the 17beta-estradiol group than in controls (5 minutes; 634.4 +/- 213.1 microg/mL v 773.1 +/- 209.3 microg/mL; 4 hours, 305.0 +/- 108.0 microg/mL v 441.3 +/- 191.6 microg/mL; p = 0.02). Systemic vascular resistance index was lower just after cardiopulmonary bypass, and cardiac index was higher postoperatively in the 17beta-estradiol group as compared with controls. CONCLUSION: Pretreatment with 17beta-estradiol can limit leukocyte activation in men after CABG surgery.

The effect of revascularisation of an ischaemic lower limb on leukotriene E4 production.

It has previously been shown that leukotriene E4 production is increased both in acute and chronic lower limb ischaemia. The aim of this study was to measure the effect of revascularisation on leuktriene E4 excretion in chronic lower limb ischaemia. Revascularisation did not affect significantly on leukotriene E4 excretion (preop. 34.9+/-7.1 pg/mg creatinine, postop. 24.5+/-4.7 pg/mg creatinine, n=10, P<0.238). We suggest that the enhanced leukotriene E4 production continues after revascularisation which may have a therapeutical implication.

Cytokine responses in patients undergoing coronary artery bypass surgery after ischemic preconditioning.

OBJECTIVE: The release of proinflammatory cytokines has been shown to be associated with the development of complications after coronary artery bypass grafting with cardiopulmonary bypass. The purpose of the present study was to establish whether ischemic preconditioning (IP) could limit inflammatory cytokines release in patients undergoing elective coronary artery bypass surgery. METHODS: Twenty-two patients with multiple-vessel coronary artery disease and stable angina admitted for first-time elective coronary artery bypass surgery were randomized into control or ischemic preconditioning groups. Patients in the IP group were exposed to two cycles of two-minute myocardial ischemia, followed by three minutes of reperfusion, at the beginning of the revascularization operation, before the cross-clamping and ischemic period used for coronary artery bypass graft anastomosis. Peripheral plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 were measured perioperatively. RESULTS: Significant elevation of IL-6, IL-8 and IL-10 were observed in both groups after reperfusion. Ischemic preconditioning has no effect on cytokine release in the early stage after reperfusion. Arterial blood IL-6 levels in the preconditioning group were significantly lower than in controls at 20 h after declamping (52.93 +/- 9.79 vs 96.04 +/- 17.56 pg/ml, p < 0.05). CONCLUSIONS: The results indicate that ischemic preconditioning results in no effect on systemic inflammatory cytokine release in the early stage but a delayed reduction in IL-6 levels at 20 h after reperfusion.

Pump prime aprotinin fails to limit proinflammatory cytokine release after coronary artery bypass surgery.

BACKGROUND: The purpose of this study was to establish whether pump prime aprotinin could limit the cytokine responses in patients undergoing elective coronary artery bypass surgery. METHODS: Twenty-one patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg aprotinin in the pump prime. Leukocyte count, creatine kinase cardiac isoenzyme (CK-MB), cytokine production and postoperative blood loss were analyzed perioperatively and compared with preoperative values. RESULTS: The peak level of leukocyte count was lower in the aprotinin group than in controls (9.3 +/- 0.58 vs 11.2 +/- 0.68 x 10(9)/L, p = 0.01). Interleukin (IL)-6 and IL-8 did not differ significantly between the groups throughout the study period. Plasma IL-10 levels were higher in the controls than in the aprotinin group at 5 min (49.6 +/- 24.9 vs 8.13 +/- 2.8 pg/ml, p = 0.01) after reperfusion. CONCLUSION: Pump prime aprotinin fails to limit proinflammatory cytokine response in circulating blood.

Cytokine responses and myocardial injury in coronary artery bypass grafting.

OBJECTIVE: Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery, and it may contribute to postoperative complications and even multiple organ dysfunction. We here compared the cytokine responses and the degree of myocardial injury after coronary artery bypass grafting with or without cardiopulmonary bypass. METHODS: Nine patients underwent off-pump revascularization and 13 with cardiopulmonary bypass. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-10 were measured before anesthesia induction, and 5 min, 1, 4, and 20 h after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were also measured after the operation. RESULTS: Levels of TNF-alpha were low in both groups. A delayed elevation of IL-6 was noted in the off-pump group. IL-8 and IL-10 levels were significantly higher in the CPB than in the off-pump patients after reperfusion (p=0.006 and 0.001 respectively). Postoperative CK-MB levels were significantly higher in the CPB than in the off-pump group (p=0.001). Cytokine levels correlated with CK-MB values. CONCLUSION: The results indicated that off-pump revascularization was associated with reduced cytokine responses and less severe myocardial injury. The degree of myocardial injury, as defined by CK-MB release, correlated with cytokine release. Intervention designed to reduce cytokine responses in cardiac surgery may be advantageous for patients with severe comorbidity.

Imaging of experimental end-to-side anastomoses in a cast model.

OBJECTIVE: To evaluate cast models in the imaging of experimental end-to-side anastomoses. DESIGN: Experimental study. SETTING: Teaching hospital, Finland. INTERVENTIONS: 20 non-stenosed and 10 stenosed end-to-side anastomoses were constructed using a Dacron prosthesis 8 mm in diameter. Cast models were made of all anastomoses, and anteroposterior and oblique projection radiographs were taken of them. Cross-sectional radiographs were also taken of the stenosed anastomoses. MAIN OUTCOME MEASUREMENTS: The diameters and areas of anastomoses were measured on the radiographs and compared with the corresponding measurements of the casts. RESULTS: No filling defects were observed in any of the cast models and only minor differences were found between the corresponding measurements of the anteroposterior and oblique projection radiographs and casts. The lower density of the contrast medium in the stenotic anastomoses indicated a stenosis. In the cross-sectional radiographs of the stenotic anastomoses there was a significant reduction (p < 0.001) both in the diameter and the area, the mean of which was 63% and the median 61%. CONCLUSIONS: Radiographs of cast models look promising in imaging of experimental end-to-side anastomoses when cross-sectional projections are also used.

Carotid stenosis and abdominal aortic aneurysm at the follow-up examination in patients treated for acute extremity ischaemia.

BACKGROUND: To evaluate survivors treated for acute extremity ischaemia as a risk-group for carotid stenosis and abdominal aortic aneurysm at the follow-up examination. EXPERIMENTAL DESIGN: Clinical study with median follow-up of 14 (8-32) months. SETTING: Central Hospital of Central Finland. PATIENTS: Eighteen survivors with median age of 77 (51-92) years treated for acute extremity ischaemia during two-year period intended to a separate follow-up examination median 14 (8-32) months after the acute episode of vascular occlusion. Ischaemia was considered as acute in 14 patients and acute on chronic in four patients. INTERVENTIONS: Thromboembolectomy was the primary intervention excluding two patients with distal upper limb ischaemia who were treated by intravenous heparin. MEASURES: Clinical examination, duplex scanning of carotid bifurcation and sonography of abdominal aorta were performed at the follow-up examination. RESULTS: Significant asymptomatic carotid stenosis >60% was found in four patients (22%), two of these patients had significant bilateral carotid stenosis. One patient (60%) had abdominal aortic aneurysm of 5.2 cm. CONCLUSIONS: In survivors treated for acute extremity ischaemia asymptomatic carotid stenosis >60% was found with significantly increased prevalence compared with general population and with equal prevalence when compared with patients with peripheral vascular disease. Occurrence of abdominal aortic aneurysm was parallel with findings in screening surveys.

Weekly and seasonal variation of hospital admissions and outcome in patients with acute lower limb ischaemia treated by surgical and endovascular means.

BACKGROUND: The aim of this study was to investigate weekly and seasonal variation of hospital admissions, major amputations and mortality in patients treated for acute leg ischaemia by surgical and endovascular procedures. EXPERIMENTAL DESIGN: Retrospective study. SETTING: University (5), central (16) and district (4) hospitals participating in the Finnish national vascular registry Finnvasc. PATIENTS: 1550 patients treated for acute leg ischaemia on the basis of the registry. INTERVENTIONS: Surgical or endovascular revascularisation. MEASURES: Day of the week of hospital admission, major amputation and death. RESULTS: The weekly pattern of the hospital admissions was significantly non-uniform with a Monday peak and a weekend nadir. A tendency towards more hospital admissions in the winter season was found. PATIENTS hospitalised on Thursday or Friday tended to have a lower amputation rate compared to those hospitalised in any other day of week. The highest amputation and mortality rates were observed in the summer season. CONCLUSIONS: PATIENTS with acute leg ischaemia seek medical help in a non-uniform weekly and seasonal pattern with varying outcomes.

Resting ECG changes in long term survivors after carotid endarterectomy.

OBJECTIVE: To evaluate the prevalence of resting ECG findings preoperatively and at the follow-up examination in long term survivors after carotid endarterectomy and to find out possible alteration in ECG pattern between preoperative and follow-up ECG records. SETTING: Tampere University Hospital. PATIENTS: 150 patients intended to control examination. There were 97 men and 53 women with the mean age of 63.7 years. INTERVENTIONS: Carotid endarterectomy. MEASURES: Preoperative and follow-up ECG records were classified according to Minnesota coding system. RESULTS: No reportable ECG items were found in 92.0% of patients preoperatively and in 78.5% at the follow-up examination. In 13.3% of patients ECG pattern was changed during the follow-up. Q-QS-changes were found in 6.7% of patients preoperatively and in 16.1% of patients at the follow-up examination. Atrial fibrillation appeared in 4.7% of patients during the follow-up. One new RBBB was found at the follow-up ECG. CONCLUSIONS: In this selected material resting ECG changes in long term survivors after carotid endarterectomy were relatively few. ECG changes found were mostly suggestive of ischemic heart disease and progression to more frequent ischemic changes during the follow-up was obvious.

Percutaneous transluminal angioplasty increases thromboxane A2 production in claudicants.

Percutaneous transluminal angioplasty is an acute, local stimulus to platelets which activation is regarded as an important factor for a later restenosis. The balance between the production of prostacyclin and thromboxane A2 is of (patho)physiological importance due to their opposite actions on vascular tone and platelet reactivity. In this study we investigated the influence of percutaneous transluminal angioplasty of the peripheral arteries on prostacyclin and thromboxane A2 productions in vivo by measuring the excretions of their urinary index metabolites, 2,3-dinor-6-ketoprostaglandin F1 alpha and 11-dehydrothromboxane B2, respectively, in 10 patients. We found a twofold increase in thromboxane A2, but no significant change in prostacyclin, production after peripheral transluminal angioplasty which shifted prostacyclin/thromboxane A2 balance to the direction of thromboxane A2 formation. This gives theoretical support to the use of thromboxane A2 synthase inhibitors and receptor antagonists as well as prostacyclin analogues in combination with peripheral percutaneous transluminal angioplasty to prevent thrombosis and restenosis.

Prostacyclin and thromboxane A2 synthesis are increased in acute lower limb ischaemia.

Prostacyclin (PGI2) and thromboxane A2 (TXA2) play an important role in the pathophysiology of various cardiovascular diseases. The balance between PGI2 and TXA2 regulates the interaction between platelets and the vessel wall in vivo. In this study we measured PGI2 and TXA2 synthesis by analysing their urinary index metabolites 2,3-dinor-6-keto-PGF1 alpha and 11-dehydro-TXB2, respectively, in acute (10 patients) and chronic (10 patients) lower limb ischaemia. Both PGI2 and TXA2 synthesis were increased about two-fold in patients with acute lower limb ischaemia compared to chronic lower limb ischaemia. However, the PGI2/TXA2 ratio was more or less the same in acute and chronic lower limb ischaemia. In patients with acute lower limb ischaemia caused by thrombotic occlusion, PGI2 and TXA2 formation were about two times higher than in patients with acute lower limb ischaemia caused by embolic occlusion. Elevation of PGI2 and TXA2 synthesis in acute lower limb ischaemia may reflect increased platelet-vascular wall interactions without changing the PGI2/TXA2 ratio.

Prevalence and predictive value of ECG findings in acute extremity ischemia.

OBJECTIVE: To determine the prevalence and predictive value of ECG findings in patients treated surgically for acute extremity ischemia. EXPERIMENTAL DESIGN: Retrospective study with follow-up for one month. SETTING: Tampere University Hospital, Jyväskylä Central Hospital. PATIENTS: 114 patients with acute extremity ischemia treated surgically. INTERVENTIONS: Emergency thromboembolectomy was performed to all patients. MEASURES: ECGs, taken preoperatively at the emergency department, were analysed according to the Minnesota code. Death was regarded as the endpoint of the study. RESULTS: ST-J depression (60.5%) and T-wave inversion (71.9%) were the most common single findings. The ECG was considered suggestive of ischemic heart disease in 64.0% of patients. The prevalence of atrial fibrillation was 37.7%. Atrial fibrillation was found in 25.0% of patients with acute thrombotic occlusion and in 43.6% of patients with embolic occlusion (chi 2 = 3.6, df = 1, p = 0.057). The ECG was suggestive of ischemic heart disease in 87.5% of patients who died within a month compared to 60.2% in those still alive (chi 2 = 4.4, df = 1, p = 0.034). In logistic regression analysis atrial fibrillation was found to increase the risk of mortality (B = 0.93, df = 1, p = 0.002); odds ratio 2.6 (95% CI 1.4-4.7). CONCLUSION: Most patients with acute extremity ischemia had significant ECG findings with low prevalence of AF reflecting increased ratio of thrombotic occlusions. AF and ECG suggestive of ischemic heart disease were also associated to poor short-term prognosis. We think that acute thrombosis should be suspected in most patients with acute extremity ischemia.

Prognostic value of preoperative C-reactive protein concentration and white cell count in acute extremity ischaemia.

OBJECTIVE: To find out if the C-reactive protein (CRP) concentration and the white cell count (WCC) are of any prognostic value in patients with acute extremity ischaemia. DESIGN: Retrospective study. SETTING: Tampere University Hospital and Jyväskylä Central Hospital, Finland. SUBJECTS: 129 patients with acute extremity ischaemia. MAIN OUTCOME MEASURES: Preoperative CRP concentration, white cell count, packed cell volume, serum creatinine concentration, major amputation and death. RESULTS: The median (range) CRP concentration was 50.0 (3-271) mg/l in the 28 patients who underwent major amputation or died (group 1) and 11.0 (1.175) mg/l in the 65 patients who survived with viable limbs (group 2) (p = 0.007). The median (range) WCC was 13.1 (5.9-42.0) x 10(9)/l in group 1 (30 patients) and 9.5 (2.2-23.9) x 10(9)/l in group 2 (79 patients) (p < 0.001). The cut-off point of 20 mg/l for CRP and 11.0 x 10(9)/l for WCC had negative predictive values of 0.83 and 0.85 for amputation and mortality, respectively. CONCLUSION: Preoperative CRP concentration and WCC correlated with limb salvage and mortality in patients with acute extremity ischaemia.

Outcome of surgical treatment in acute upper limb ischaemia.

During a 26 years' period, 547 thromboembolectomies were undertaken for acute limb ischaemia. The portion of upper limb ischaemia was 17.7% (97/547). The annual incidence of surgically treated acute upper limb ischaemia was 1.3 cases/100,000/year during the last 15 years of study period. There were 91 patients, 45 males and 46 females, ranging from 17 to 92 years with a median age of 73 years. Pulselessness (96), coldness (94), pain (85), paraesthesia (45) and dysfunction (45) of the affected limb were the main symptoms. The right upper limb was more often affected (59/38, P < 0.05). An embolus originating from the heart was the reason for the ischaemia in 71 cases, while in 11 cases the occlusion was caused by a local thrombosis. In 15 cases the origin of the embolus remained unsolved. In five cases an additional arterial reconstruction was needed to restore the circulation. Reembolectomy of the same limb was needed in five cases, and additionally in two patients, a third embolectomy was unavoidable. A secondary humeral amputation was necessary for one patient. Eleven patients (11.3%) died within 30 days and of these nine did so from recurrent embolism. The mortality was not related to the duration of the ischaemia, but rather to patients' general condition. During a mean follow-up time of 50 weeks a good functional result was achieved in 78 cases (80.4%). The clinical results in ischaemia caused by embolism are markedly better than those of local thrombosis (P < 0.001).