Biomedical subjects

M A Hassett

Publications and source records attributed to M A Hassett.

4 recordsLinked to original sources

PubMed1987

Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits.

Plasma levels of a fast-acting plasminogen activator inhibitor (PAI), which neutralizes both tissue plasminogen activator (t-PA) and urokinase, are markedly increased in endotoxin-treated rabbits. The ability of this inhibitor to prevent the fibrinolysis that occurs after a thrombogenic stimulus was investigated in a rabbit model. Normal and endotoxin-treated male New Zealand rabbits were infused with ancrod, an enzyme that causes noncrosslinked fibrin formation in vivo. Ancrod stimulated t-PA activity by 90% in normal rabbits and caused hypofibrinogenemia but did not increase PAI levels or induce fibrin deposition in target organs. Rabbits injected with endotoxin (10 micrograms/kg) showed an increase in PAI from less than 1 to 32 U/mL 4 hours later. When ancrod was infused at this time, 90% of the rabbits developed renal fibrin thrombi. Fibrin deposition was recorded in 40% of the rabbits that received a lower dose of endotoxin (1.0 microgram/kg) and had a PAI level of 14 U/ml at the time of ancrod infusion 4 hours later. Fibrin deposition did not occur in the endotoxin-treated rabbits that received normal saline. These data suggest that high levels of PAI inhibit fibrinolysis in vivo, thereby promoting fibrin clot deposition following a thrombogenic stimulus.

Ancrod↗

PubMed1986

The rabbit as a model for studies of fibrinolysis.

When compared to man, the rabbit shows marked prolongation of the dilute whole blood clot lysis time and an attenuated increase in plasminogen activator (PA) after the infusion of desmopressin (DDAVP). The levels of specific components of the plasma fibrinolytic system of the rabbit were compared to those in human plasma to ascertain their role in the differences between species. PA activity and plasminogen levels were similar in the two species. Anti-plasmin and plasminogen activator inhibitor (PAI) activity were lower in the rabbit than in man. The rabbit PAI, apparently similar to that described in man, was not increased by DDAVP infusion. The disparity between man and rabbit with respect to the lysis times of dilute blood clots and response to DDAVP cannot be explained by differences in functional plasma levels of inhibitors or activators of the fibrinolytic system.

Animals↗

PubMed1985

Structural and functional characterization of the inhibition of urokinase by alpha 2-macroglobulin.

We have investigated the interaction of alpha 2-macroglobulin (alpha 2M) with the serine proteinase urokinase, an activator of plasminogen. Urokinase formed sodium dodecyl sulfate stable complexes with purified alpha 2M and with alpha 2M in plasma. These complexes could be visualized after polyacrylamide gel electrophoresis by protein blots using 125I-labeled anti-urokinase antibody or by fibrin autography, a measure of fibrinolytic activity. According to gel electrophoretic analyses under reducing conditions, urokinase cleaved alpha 2M subunits and formed apparently covalent complexes with alpha 2M. Urokinase cleaved only about 60% of the alpha 2M subunits maximally at a mole ratio of 2:1 (urokinase: alpha 2M). Binding of urokinase to alpha 2M protected the urokinase active site from inhibition by antithrombin III-heparin and inhibited, to a significant extent, plasminogen activation by urokinase. Reaction of urokinase with alpha 2M caused an increase in intrinsic protein fluorescence and, thus, induced the conformational change in alpha 2M that is characteristic of its interactions with active proteinases. Our results indicate that both in plasma and in a purified system the alpha 2M-urokinase reaction is functionally significant.

Antigen-Antibody Complex↗

PubMed1980

Transient QRS changes simulating acute myocardial infarction.

The purpose of this study was to determine the characteristics and incidence of abrupt occurrence of abnormal initial QRS forces that cannot be explained by acute myocardial infarction or left or right ventricular overload. Computerized data from 3175 patients with suspected acute infarction were reviewed to identify those in whom the ECGs revealed QRS complexes considered to be diagnostic (Q wave or markedly diminished R wave) in the presence of persistently normal profiles of both creatine kinase and lactic dehydrogenase isoenzymes. Lead misplacement had been minimized by obtaining multispace tracings and vectorcardiograms. Eight patients (0.25%) were identified. The abnormal forces were confined to leads V 1-3 in six, V 4-6 in one, and involved all precordial leads in the last. These QRS changes resolved completely within 6 days in all eight patients, which suggests that they did not have an acute infarction. This theory was supported by postmortem examination in one patient. An extremely low incidence (0.25%) has been documented for a syndrome characterized by transient loss of initial anterior forces with persistently normal isoenzyme profiles. Although no etiology could be determined, a transient conduction block of the septal fascicle of the left bundle could have been the cause in seven of the eight patients.

Electrocardiography↗