Regulation of arterial thrombolysis by plasminogen activator inhibitor-1 in mice

BACKGROUND: Platelet-rich arterial thrombi are resistant to lysis by plasminogen activators. However, the mechanisms underlying thrombolysis resistance are poorly defined. Plasminogen activator inhibitor-1 (PAI-1), which is present in plasma, platelets, and vascular endothelium, may be an important determinant of the resistance of arterial thrombi to lysis. However, in vitro studies examining the regulation of platelet-rich clot lysis by PAI-1 have yielded inconsistent results. METHODS AND RESULTS: We developed a murine arterial injury model and applied it to wild-type (PAI-1 [+/+]) and PAI-1-deficient (PAI-1 [-/-]) animals. FeCl3 was used to induce carotid artery thrombosis. Thrombi consisted predominantly of dense platelet aggregates, consistent with the histology of thrombi in large-animal arterial injury models and human acute coronary syndromes. To examine the role of PAI-1 in regulating endogenous clearance of platelet-rich arterial thrombi, thrombi were induced in 22 PAI-1 (+/+) mice 14 PAI-1 (-/-) mice. Twenty-four hours later, the amount of residual thrombus was determined by histological analysis of multiple transverse sections of each artery. Residual thrombus was detected in 55 of 85 sections (64.7%) obtained from PAI-1 (+/+) mice compared with 19 of 56 sections (33.9%) from PAI-1 (-/-) mice (P=.009). Computer-assisted planimetry analysis revealed that mean thrombus cross-sectional area was 0.033+/-0.0271 mm2 in PAI-1 (+/+) mice versus 0.016+/-0.015 mm2 in PAI-1 (-/-) mice (P=.048). CONCLUSIONS: PAI-1 is an important determinant of thrombolysis at sites of arterial injury. Application of this model to other genetically altered mice should prove useful for studying the molecular determinants of arterial thrombosis and thrombolysis.     

A multiyear workplace-monitoring program for refractory ceramic fibers: findings and conclusions

Results of a monitoring program carried out by members of the Refractory Ceramic Fibers Coalition as part of a Consent Agreement with the U.S. Environmental Protection Agency to measure workplace concentrations of refractory ceramic fiber (RCF) are presented. More than 700 personal monitoring samples were collected and analyzed annually from workers in RCF production and processing plants, as well as from those employed by customers/end users. The data indicate that (i) approximately 90% of time-weighted average (TWA) workplace concentrations are below the industry's recommended exposure guideline of 1 fiber per cubic centimeter TWA; (ii) workplace concentrations vary with functional job category; (iii) concentrations are approximately lognormally distributed; (iv) workplace concentrations are generally decreasing; (v) there are significant differences in workplace concentrations among plants operated by both RCF producers and customers; (vi) equations can be developed to interconvert data analyzed using different measurement techniques and counting rules; (vii) usage of respirators varies with the functional job category of the worker and the average fiber concentration; and (viii) workplace samples differ from those used in animal inhalation experiments in terms of the ratio of respirable particles to fibers.