title: Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke.
abstract: BACKGROUND
  Matrix metalloproteinase (MMP) expression is related to blood brain barrier disruption after cerebral ischemia. Moreover, MMP inhibitors reduce hemorrhagic transformation (HT) after embolic ischemia in tissue plasminogen activator (t-PA)-treated animals. We aimed to correlate plasmatic MMP levels with the appearance of intracranial bleeding complications in stroke patients treated with t-PA.
  
  
  RESULTS
  Serial MMP-2 and MMP-9 determinations were performed (ELISA, ng/mL) in 41 strokes involving the middle cerebral artery territory in patients who received t-PA within 3 hours of stroke onset. Blood samples were obtained at baseline (pretreatment) and at 12 and 24 hours after symptom onset. Hemorrhagic events were classified according to CT criteria (petechial hemorrhagic infarctions [HI, 1 to 2] and large parenchymal hemorrhages [PH, 1 to 2]). Brain CT scan was obtained at 48 hours or when a neurological worsening occurred. HT was present in 36.5% of the patients (24.4% HI and 12.1% PH). MMP-2 values were unrelated to any subtype of HT. The highest baseline MMP-9 level (normal range <97 ng/mL) corresponded to patients who later developed a PH (PH: 270.2+/-87.8, non-HT: 126.3+/-127.5, HI: 94.6+/-88.7; P=0.047). A graded response was found between mean baseline MMP-9 levels and the degree of bleeding (HI-1=37.4; HI-2=111.0; PH-1=202.5; PH-2=337.8). Baseline MMP-9 was the most powerful predictor of PH appearance in the multiple logistic regression model (OR= 9.62; CI 1.31 to 70.26; P=0.025).
  
  
  CONCLUSIONS
  Baseline MMP-9 level predicts PH appearance after t-PA treatment. Therefore, we suggest that MMP determination may increase the safety profile for thrombolysis and, in the future, anti-MMP drugs might be combined with t-PA to prevent hemorrhagic complications.
authors.affiliation: Cerebrovascular Unit, Vall d'Hebron Hospital, Barcelona, Spain. 31862jmv@comb.es
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Jasone
authors.initials: J
authors.lastname: Monasterio
authors.forename: Sonia
authors.initials: S
authors.lastname: Abilleira
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arenillas
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.forename: Manolo
authors.initials: M
authors.lastname: Quintana
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D018450:Disease Progression; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007118:Immunoassay; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000201:enzymology; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000517:prevention & control; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020521:Stroke / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9