Vaginal Lactoferrin Modulates PGE2, MMP-9, MMP-2, and TIMP-1 Amniotic Fluid Concentrations.

Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n = 57) or treated with LF 4 hours before amniocentesis (n = 54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p < 0.01, p < 0.005, and p < 0.001, resp.). Conversely, active MMP-2 (p < 0.0001) and MMP-2/TIMP-2 molar ratio (p < 0.001) were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563.

TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis.

BACKGROUND: The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. OBJECTIVE: To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis. METHODS: We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. RESULTS: Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively). CONCLUSION: Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity.

An unusual case of acute respiratory failure in a patient with pulmonary veins stenosis late after catheter ablation of atrial fibrillation: a case report and the review of the literature.

BACKGROUND: Atrial fibrillation (AF) can be treated with percutaneous catheter ablation procedures into the left atrium. Pulmonary veins stenosis (PV) stenosis is a severe complication of this procedure. CASE PRESENTATION: we report a case of late hemoptysis secondary to severe PV stenosis in a man who underwent AF ablation 9 months before onset of symptoms. He presented four episodes of bleeding and developed an acute respiratory failure (ARF). Parameters of respiratory mechanics and medical investigation did not show any abnormalities. Only computed tomography (CT) angiography showed stenosis of 3 out of 4 native PVs. PV balloon dilatation in all affected PVs and a stent was implanted in 1 of the 3 PVs with full restoration of respiratory function during 1 year follow-up. CONCLUSION: PV stenosis may be the underlying cause of recurrent haemoptysis after AF ablation in the presence of normal respiratory parameters. This diagnosis can be confirmed by means of CT angiography and magnetic resonance imaging can provide accurate localization of stenosis.

Balanced and unbalanced solutions modulate the release of Matrix Metalloproteinase-9 (MMP-9) from neutrophils in response to inflammatory stimuli: an in vitro study.

OBJECTIVES AND DESIGN: We investigated the effect of balanced (BS) and unbalanced (UBS) solutions in the absence or presence of hydroxyethyl starch (HES) on neutrophil functionality, evaluating the release of matrix metalloproteinase (MMP)-9, myeloperoxidase (MPO), and MMP-8. MATERIALS AND METHODS: Neutrophils were isolated by gradient centrifugation and dextran sedimentation and incubated in BS or UBS without or with HES, in the absence or presence of Interleukin-8 (IL-8) or Lipopolysaccharide (LPS). MMP-9, MPO, and MMP-8 were assayed by commercially available ELISA kits. RESULTS: There was not any influence of volume replacement solutions on the release of the enzymes from resting neutrophils. After IL-8 stimulation, the release of MMP-9 was higher in BS than in UBS or RPMI-1640, whereas HES enhanced its release regardless of the composition. After LPS stimulation, the release of MMP-9 was higher in both UBS and BS than RPMI-1640, but HES brought its release back to physiological conditions. No difference was found in the release of MPO and MMP-8 after stimulation with IL-8 or LPS. CONCLUSION: Volume replacement solutions might have an impact on the release of MMP-9 depending on the inflammatory milieu, suggesting that the use of balanced or unbalanced solutions is not a neutral choice.

Inspiratory pressure waveform influences time to failure, respiratory muscle fatigue, and metabolism during resistive breathing.

Increased ventilatory work beyond working capacity of the respiratory muscles can induce fatigue, resulting in limited respiratory muscle endurance (Tlim ). Previous resistive breathing investigations all applied square wave inspiratory pressure as fatigue-inducing pattern. Spontaneous breathing pressure pattern more closely approximate a triangle waveform. This study aimed at comparing Tlim , maximal inspiratory pressure (PImax ), and metabolism between square and triangle wave breathing. Eight healthy subjects (Wei = 76 ± 10 kg, H = 181 ± 7.9 cm, age = 33.5 ± 4.8 years, sex [F/M] = 1/7) completed the study, comprising two randomized matched load resistive breathing trials with square and triangle wave inspiratory pressure waveform. Tlim decreased with a mean difference of 8 ± 7.2 min (p = 0.01) between square and triangle wave breathing. PImax was reduced following square wave (p = 0.04) but not for triangle wave breathing (p = 0.88). Higher VO2 was observed in the beginning and end for the triangle wave breathing compared with the square wave breathing (p = 0.036 and p = 0.048). Despite higher metabolism, Tlim was significantly longer in triangle wave breathing compared with square wave breathing, showing that the pressure waveform has an impact on the function and endurance of the respiratory muscles.

Effect of expiratory flow limitation on ventilation/perfusion mismatch and perioperative lung function during pneumoperitoneum and Trendelenburg position.

BACKGROUND: Laparoscopic surgery and Trendelenburg position may affect the respiratory function and alter the gas exchange. Further the reduction of the lung volumes may contribute to the development of expiratory flow limitation (EFL). The latter is associated with an increased risk of postoperative pulmonary complications. Our aim was to investigate the incidence of EFL and to evaluate its effect on pulmonary function and intraoperative V/Q mismatch. METHODS: This is a prospective study on patients undergoing elective laparoscopic gynecological surgery. We evaluated respiratory mechanics, V/Q mismatch and presence of EFL after anesthesia induction, during pneumoperitoneum and Trendelenburg position and at the end of surgery. Intraoperative gas exchange and hemodynamic were also recorded. Clinical data were collected until seven days after surgery to evaluate the onset of pulmonary postoperative complications (PPCs). RESULTS: Among the 66 patients enrolled, 25/66 (38%) exhibited EFL during surgery, of whom 10/66 (15%) after anesthesia induction, and the remaining 15 patients after pneumoperitoneum and Trendelenburg position. Median PEEP able to reverse flow limitation was 7 [7-10] cmH2O after anesthesia induction and 9 [8-15] cmH2O after pneumoperitoneum and Trendelenburg position. Patients with EFL had significantly higher shunt (17 [2-25] vs. 9 [1-19]; P=0.05), low V̇/Q̇ (27 [20-70] vs. 15 [10-22]; P=0.05) and high V̇/Q̇ (10 [7-14] vs. 6 [4-7]; P=0.024). At the end of surgery, only high V/Q was significantly higher in EFL patients. Further, they exhibited higher incidence of postoperative pulmonary complication (48% (12/25) vs. 15% (6/41), P=0.005), hypoxemia and hypercapnia (80% [20/25] vs. 32% [13/41]; P<0.001). CONCLUSIONS: Expiratory flow limitation is a common phenomenon during gynecological laparoscopic surgery associated with worsen gas exchange, increased V/Q mismatch and altered lung mechanics. Our study showed that patients experiencing EFL during surgery showed a higher risk for PPCs.

Pulmonary function and expiratory flow limitation in acute cervical spinal cord injury.

OBJECTIVE: To identify the nature of the changes of respiratory mechanics in patients with middle cervical spinal cord injury (SCI) and their correlation with posture. DESIGN: Clinical trial. SETTING: Acute SCI unit. PARTICIPANTS: Patients with SCI (N=34) at C4-5 level studied within 6 months of injury. INTERVENTIONS: Patients were assessed by the negative expiratory pressure test, maximal static respiratory pressure test, and standard spirometry. MAIN OUTCOME MEASURES: The following respiratory variables were recorded in both the semirecumbent and supine positions: (1) tidal expiratory flow limitation (TEFL); (2) airway resistances; (3) mouth occlusion pressure developed 0.1 seconds after occluded inspiration at functional residual capacity (P(0.1)); (4) maximal static inspiratory pressure (MIP) and maximal static expiratory pressure (MEP); and (5) spirometric data. RESULTS: TEFL was detected in 32% of the patients in the supine position and in 9% in the semirecumbent position. Airway resistances and P(0.1) were much higher compared with normative values, while MIP and MEP were markedly reduced. The ratio of forced expiratory volume in 1 second to forced vital capacity was less than 70%, while the other spirometric data were reduced up to 30% of predicted values. CONCLUSIONS: Patients with middle cervical SCI can develop TEFL. The presence of TEFL, associated with increased airway resistance, could increase the work of breathing in the presence of a reduced capacity of the respiratory muscles to respond to the increased load. The semirecumbent position and the use of continuous positive airway pressure can be helpful to (1) reduce the extent of TEFL and avoid the opening/closure of the small airways; (2) decrease airway resistance; and (3) maintain the expiratory flow as high as possible, which aids in the removal of secretions.

Mechanical ventilation and COPD: from pathophysiology to ventilatory management.

In the chronic obstructive pulmonary disease (COPD), lung and chest-wall morphological alterations determine important and peculiar approaches to mechanical ventilation. Lung emphysema and reduced elastic recoil increase expiratory time, thus worsening dynamic hyperinflation, while airways chronic inflammation rises resistances and can determine distal air-trapping. Muscle wasting and fast fibers prevalence can result in weakness and in an earlier onset of muscle fatigue, prolonging the weaning process. In this narrative review, we explored the connection between altered pathophysiology and necessity for respiratory assistance in COPD, focusing on non-invasive and invasive respiratory management, lung monitoring and weaning difficulties.

Platelet morphological indices on Intensive Care Unit admission predict mortality in septic but not in non-septic patients.

BACKGROUND: Thrombocytopenia is associated with worse outcomes in critically ill patients. The clinical relevance of other platelets indices is less studied. We investigated the ability of the platelets distribution width (PDW) and the mean platelet volume (MPV) to predict mortality in critically ill patients. We hypothesized that the prognostic values of PDW and MPV could be different in septic and non-septic patients. METHODS: We prospectively analyzed patients with an expected ICU length of stay ≥48 hours. Repeated measurements of PDW and MPV were considered (on ICU admission and up to day 5 thereafter). The primary outcome was to investigate the ability of PDW and MPV to predict 90-day mortality in septic and non-septic patients. RESULTS: We included in the study 234 patients of which 31% patients were septic. 90-day mortality was 39% in septic and 27% non-septic patients. PDW and MPV values on admission were 12.5±2.5% and 10.7±1.1 fL, respectively. The AUROC of PDW values on admission to predict 90-day mortality in septic patients was 0.813, being higher than those in non-septic patients (0.550, P<0.001). Similarly, the AUROC for MPV in septic patients was higher than non-septic patients (0.55, P<0.001). The combined analysis of platelets morphological indices and lactate improved the predictive accuracy (PDW and lactate AUROC=0.870; MPV and lactate AUROC=0.867). CONCLUSIONS: Platelet morphological indices are independent predictor of 90-day mortality in septic patients but not in non-septic patients. A combined analysis of platelets morphological indices and lactate in septic patients resulted in improved prediction of mortality.

Fast skeletal troponin I, but not the slow isoform, is increased in patients under statin therapy: a pilot study.

INTRODUCTION: Statin therapy is often associated with muscle complaints and increased serum creatine kinase (CK). However, although essential in determining muscle damage, this marker is not specific for skeletal muscle. Recent studies on animal models have shown that slow and fast isoforms of skeletal troponin I (ssTnI and fsTnI, respectively) can be useful markers of skeletal muscle injury. The aim of this study was to evaluate the utility of ssTnI and fsTnI as markers to monitor the statin-induced skeletal muscle damage. MATERIALS AND METHODS: A total of 51 patients (14 using and 37 not using statins) admitted to the intensive care unit of the University of Ferrara Academic Hospital were included in this observational study. Serum activities of CK, aldolase, alanine aminotransferase and myoglobin were determined by spectrophotometric assays or routine laboratory analysis. Isoforms ssTnI and fsTnI were determined by commercially available ELISAs. The creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) were evaluated as biomarkers of cardiac muscle damage by automatic analysers. RESULTS: Among the non-specific markers, only CK was significantly higher in statin users (P = 0.027). Isoform fsTnI, but not ssTnI, was specifically increased in those patients using statins (P = 0.009) evidencing the major susceptibility of fast-twitch fibres towards statins. Sub-clinical increase in fsTnI, but not CK, was more frequent in statin users (P = 0.007). Cardiac markers were not significantly altered by statins confirming the selectivity of the effect on skeletal muscle. CONCLUSIONS: Serum fsTnI could be a good marker for monitoring statin-associated muscular damage outperforming traditional markers.

The prognostic role of red blood cell distribution width in transfused and non-transfused critically ill patients.

BACKGROUND: Red blood cell distribution width (RDW) value is gaining popularity as a prognostic factor in critically ill patients. However, its role in transfused patients is unclear. The aim of this study was to evaluate the predictive value of Red blood cell distribution width (RDW) on Intensive Care Unit (ICU) admission for 90-day mortality among either transfused or non-transfused critically ill patients. METHODS: This observational cohort study includes 286 patients with at least 48 hours of ICU length of stay. Patients were analyzed separately in two groups, depending on whether or not they were transfused in the last 72 hours before ICU admission. RESULTS: One hundred seventeen (117) patients (41%) were transfused. Patients with high RDW on admission (N.=181, 63%) had higher 90-day mortality both in non-transfused (26/87, 30% vs. 12/82, 14% P=0.03) or transfused (39/94, 41% vs. 2/23, 8% P=0.003) patients. The area under the curve of admission RDW values to predict 90-day mortality was 0.660 and 0.610 for non-transfused and transfused patients, respectively. The Youden Index analysis showed that an RDW value of 14.3% was the best cut-off to predict mortality in the non-transfused group, while 15.3% was the best cut-off in the transfused group. CONCLUSIONS: High RDW values on ICU admission are independently associated with 90-day mortality in critically ill patients regardless of previous red blood cells transfusion. However, we identified two different cut-offs of "high RDW" to be used in ICU in transfused and non-transfused patients.

Red Cell Distribution Width After Subarachnoid Hemorrhage.

BACKGROUND: High red cell distribution width (RDW) values have been associated with increased hospital mortality in critically ill patients, but few data are available for subarachnoid hemorrhage (SAH). METHODS: We analyzed an institutional database of adult (>18 y) patients admitted to the Department of Intensive Care after nontraumatic SAH between January 2011 and May 2016. RDW (normal value, 10.9% to 13.4%) was obtained daily from admission for a maximum of 7 days, from routine blood analysis. We recorded the occurrence of delayed cerebral ischemia (DCI), and neurological outcome (assessed using the Glasgow Outcome Scale [GOS]) at 3 months. RESULTS: A total of 270 patients were included (median age 54 y-121/270 male [45%]), of whom 96 (36%) developed DCI and 109 (40%) had an unfavorable neurological outcome (GOS, 1 to 3). The median RDW on admission was 13.8 [13.3 to 14.5]% and the highest value during the intensive care unit (ICU) stay 14.2 [13.6 to 14.8]%. The RDW was high (>13.4%) in 177 patients (66%) on admission and in 217 (80%) at any time during the ICU stay. Patients with a high RDW on admission were more likely to have an unfavorable neurological outcome. In multivariable regression analysis, older age, a high WFNS grade on admission, presence of DCI or intracranial hypertension, previous neurological disease, vasopressor therapy and a high RDW (OR, 1.1618 [95% CI, 1.213-2.158]; P=0.001) during the ICU stay were independent predictors of unfavorable neurological outcome. CONCLUSIONS: High RDW values were more likely to result in an unfavorable outcome after SAH. This information could help in the stratification of SAH patients already on ICU admission.

Can pre-procedure neuroaxial ultrasound improve the identification of the potential epidural space when compared with anatomical landmarks? A prospective randomized study.

BACKGROUND: Regional epidural analgesia is considered the gold standard for pain treatment in labor. However, epidural catheter placement may be a challenging procedure because of the difficulty in the palpation of anatomical landmarks, particularly in pregnant women. Pre-procedural neuroaxial ultrasound may facilitate the procedure. METHODS: A prospective randomized controlled study was conducted in a labor ward. Two groups of women undergoing epidural analgesia were randomized: Group A (N.=28), which was subjected to the loss of resistance technique, and Group B (N.=30) which was subjected to an ultrasound (US)-assisted procedure. The real depth of epidural space was calculated in both groups by measuring the needle skin-to-tip distance, while the US depth was measured only in Group B. RESULTS: The mean number of attempts in group A (3.43±3.8) was significantly higher than in Group B (1.70±0.87, P=0.019). Analysis of data from Group B revealed a strong positive correlation between the epidural real depth and US depth (r=0.88, P<0.0001). CONCLUSIONS: The US-assisted technique for epidural catheter placement for labor analgesia is safe, effective, easy to perform, and is a valuable aid to improve the identification of the epidural space compared with the palpation of anatomical landmarks and the loss of resistance technique. Pre-puncture ultrasound assessment shows the exact location of the intervertebral space, the optimal point of insertion and the tilt angle of the needle, the depth of the epidural space and any anatomical abnormalities of the spine, thereby increasing the success rate and reducing procedural complications of the blind approach.

Respiratory mechanics by least squares fitting in mechanically ventilated patients: application on flow-limited COPD patients.

OBJECTIVE: Although computerized methods of analyzing respiratory system mechanics such as the least squares fitting method have been used in various patient populations, no conclusive data are available in patients with chronic obstructive pulmonary disease (COPD), probably because they may develop expiratory flow limitation (EFL). This suggests that respiratory mechanics be determined only during inspiration. SETTING: Eight-bed multidisciplinary ICU of a teaching hospital. PATIENTS: Eight non-flow-limited postvascular surgery patients and eight flow-limited COPD patients. INTERVENTION: Patients were sedated, paralyzed for diagnostic purposes, and ventilated in volume control ventilation with constant inspiratory flow rate. MEASUREMENTS: Data on resistance, compliance, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) obtained by applying the least squares fitting method during inspiration, expiration, and the overall breathing cycle were compared with those obtained by the traditional method (constant flow, end-inspiratory occlusion method). RESULTS AND CONCLUSION: Our results indicate that (a) the presence of EFL markedly decreases the precision of resistance and compliance values measured by the LSF method, (b) the determination of respiratory variables during inspiration allows the calculation of respiratory mechanics in flow limited COPD patients, and (c) the LSF method is able to detect the presence of PEEPi,dyn if only inspiratory data are used.

Respiratory function after aortic aneurysm repair: a comparison between retroperitoneal and transperitoneal approaches.

OBJECTIVE: Elective abdominal aneurysm repair can be performed by using the transperitoneal or the retroperitoneal approach. The latter has been described as having a better outcome, reducing the impairment of respiratory function or the incidence of lung complications. Hence, the retroperitoneal approach has been proposed for treatment of medically high-risk patients. However, the superiority of one technique or the other in preserving pulmonary function has not been conclusively demonstrated. The aim of this study was to ascertain whether the retroperitoneal and the transperitoneal approaches affect respiratory function differently. DESIGN: A prospective randomized study. SETTING: Two four-bed surgical-medical ICUs of a University hospital. PATIENTS: Twenty-three consecutive patients undergoing abdominal aortic aneurysm repair were randomized to the retroperitoneal (12 patients) and transperitoneal approach (11 patients). They were studied: a). within 30 min the end of surgery; b). 8 h after the end of surgery; and c). during a T-piece tube-weaning trial. MEASUREMENTS: The comparison between the two groups was based on respiratory mechanics, partitioned between lung and chest wall components, basic spirometry, tension-time index of the inspiratory muscle, weaning indexes, and length of stay both in ICU and hospital. RESULTS: The two surgical techniques do not differ in their impact on either respiratory mechanics or inspiratory muscle function or weaning indexes. However, there was a tendency for retroperitoneal patients to stay for less time both in ICU and in the hospital. CONCLUSIONS: During the first 24 h after surgery, the postoperative impairment of respiratory function is independent of the surgical approach.

Acute respiratory failure onset in a patient with Guillain-Barré syndrome after Legionella-associated pneumonia: a case report.

A 69-year-old white man was admitted because of a clinical history of persistent cough and fever. Chest x-rays showed bilateral lung infiltrates with air bronchograms, whereas the urine antigen test resulted positive for Legionella pneumophila. The next day, he was transferred to the intensive care unit and intubated because of severe renal and respiratory distress. Neurological examination revealed distal weakness and loss of deep tendon reflexes in lower extremities. Nerve conduction studies displayed severe demyelinating sensorimotor polyneuropathy, and plasmapheresis was therefore applied with mild improvement. Few weeks after, dysphagia occurred and electrophysiologic tests showed progressive axonal involvement with spread of demyelination to the cranial nerves. The patient underwent a new plasmapheresis course and slowly reached stable clinical improvement of neurological status, which allowed him to be safely discharged. This case showed a critical onset with respiratory failure and kidney functional impairment due to L. pneumophila, subsequently disclosing Guillain-Barré syndrome.

Successful nasal intubation with a laryngeal nerve monitoring tube using bronchoscopy in a patient with plunging goiter: a case report.

BACKGROUND: The appropriate positioning of nerve integrity monitoring during thyroid surgery is of relevance. In this case report we describe our experience with accurate placement of a nerve integrity monitoring endotracheal tube, obtained by fiberoptic control, in a patient with expected difficult airway management. CASE PRESENTATION: We report the case of a 70-year-old obese woman scheduled for elective total thyroidectomy due to plunging intrathoracic goiter. The preoperative indirect laryngoscopy pointed out a massive bombè of the hypopharyngeal wall to the right and right vocal cord paralysis. The epiglottis was oedematous and the glottis could not be identified. On physical examination, the tongue was large and a Mallampati's score of 3 was determined. Hence, due to an expected difficult airway management, a nasal intubation with an electromyographic nerve integrity monitoring endotracheal tube trough fiberoptic bronchoscopy was successfully performed. CONCLUSION: Our experience suggests that nasal intubation can be safely performed by using a nerve integrity monitoring tube with the help of fiberoptic bronchoscopy.

Influence of different strategies of volume replacement on the activity of matrix metalloproteinases: an in vitro and in vivo study.

BACKGROUND: Excessive production of matrix metalloproteinase 9 (MMP-9) is linked to tissue damage and anastomotic leakage after large bowel surgery. Hence, the aim of this study was to verify whether different strategies of fluids administration can reduce MMP-9 expression. METHODS: In the in vitro experiment, the authors tested the hypothesis of a direct inhibition of MMP-9 by the fluids used perioperatively, i.e., lactated Ringer's solution, 3.4% poligeline, and hydroxyethyl starch 130/0.4. In the in vivo experiment, 36 patients undergoing surgery for colon cancer were randomly assigned to three groups to receive lactated Ringer's solution, poligeline, or hydroxyethyl starch. MMP-9 and tissue inhibitor of metalloproteinases were measured from venous blood samples; the MMP-9/tissue inhibitor of metalloproteinases ratio was calculated as an index of equilibrium between the action of MMP-9 and its inhibition. RESULTS: In the in vitro experiment, the presence of hydroxyethyl starch 130/0.4 in the MMP-9 assay system showed a strong inhibition of the enzymatic activity compared with lactated Ringer's solution. In the in vivo experiment, MMP-9 and tissue inhibitor of metalloproteinases plasma levels did not differ among the three groups at baseline, whereas those levels increased significantly at the end of surgery. At that time, the MMP-9 plasma levels and the MMP-9/tissue inhibitor of metalloproteinases ratio were significantly higher in the lactated Ringer's solution and poligeline groups than in the hydroxyethyl starch group. These results were confirmed 72 h after surgery. CONCLUSIONS: This study demonstrates that hydroxyethyl starch 130/04 decreases the circulating levels of MMP-9 in patients undergoing abdominal surgery.