Efficacy of recombinant staphylokinase inanimal experiment and clinical studyAbstractObjectives:The purpose of this study are: (1) to observe the relationship between the grades of constriction and blood pressures of rabbit femoral artery, and construct an animal model of the femoral artery thrombosis by balloon injury. (2)To observe the efficacy of r-SAK in different doses and manners of administration, and compare it with UK and r-SK. (3) To study the pharmacokinetics of r-SAK in the thrombosis model of femoral artery in rabbits and its effect on platelet quantity and plasma levels of coagulation and thrombolytic parameters. (4) To observe the thrombolytic efficacy of r-SAK on patients with acute myocardial infarction.Methods:(1) In 10 New Zealand rabbits, the right femoral arteries were gradually narrowed by nylon thread till complete occlusion, the grades of constriction and corresponding blood pressures of femoral artery were recorded. Then a 2.0-2.5mm X 20mm balloon was put into the right femoral artery to induce endothelial denudation. Thrombosis in femoral arteries were acknowledged by changes of blood pressures, angiography performed pre- and post-balloon-injury and the pathological study of injured segments. (2) 40 New Zealand rabbits were randomly assigned into control (saline lOml, 30mm), r-SAK low dose (0.25mg/kg , 30mm), medial dose (0.5mg/kg , 30mm), high dose (1 .0mg/kg , 30mm), single bolus (0.5mg/kg , 2mm), conjunctive therapy (initiated with heparin 200UIkg, followed by infusion of r-SAK 0.5mg/kg for 30min,subsequently infused heparin 5OUIkg/hr to endpoint), UK (3.0 X lO4UIkg, 30mm) and r-SK (3.0 X lO4UIkg, 30mm) groups. The thrombosis model of right femoral artery in rabbitswa made by balloon injUry, study drugs were infused throughparallel-ear vein l20min postballooninjmp, recanaliZation offemoral arteries were apPrved by changes of blood pressures,angiograPhy perfOrmed pre- and posttwmbolysis and thepathological stUdy of the injured segInents. Blood samPles werecollected at a series of time Pre- and posttwmbolysis tOdetermine the plasma levels of rSAK(in control and rSAKgrouPs ), platelet quantity, PT, APTT,TT and the plasma levelsof fibrinogen, plasminogen, Q,-antiplasndn and D-dimer. (3)Five AMI patients were enrolled in clinical stUdy, and they weeal1 treated with l5 mg rSAK combined with illtravenousheParin, the patCncy StatUs of infarct-related alleries poStthrombolysis were determined by coronary artery angiography.The relief of chest pain, aPPeaiance of reperfusion arrhythmia,change of ST-segInot and the time to peak plasma leveI ofmyocardial Wes were recorded. In addition, the relatedcomPlications and cardac events were followed uP whenever itpresented.ResuIt8: (l) Systolic and pulse blood Pressures dropedin righ femoral artery while its section area was constricted by90 %. Pulse pressure reduced to zero when the artery wasligated, with a simultaneous drop of the diastolic and meanblood pressures. (2) The Systolic and pulse blood pressures inrigh femoral mp droPPed sighficantiy 5 minues late of theballoon injury, and the pulse pressure reduced tO zero or nearzero 90 minutes after the injury, Wth a simultaneous decrease ofthe diastolic and mean blood pressures. Both the femoral arteryangiograPhy and histOlogical examination shOWed that thethrombus was created in righ femoral arteries and the arteriallumen was occluded comPletely. (3) In r-SAK grouPs, peakpressure-time curves Presented after thrombolysis, the pulse..pressures m ngh femoral arteries markedly eIilianced to morethan 50% of that in left femora arteries in some rabbits, withlow dose grouP (n=2), medial dose grOuP (n=5), high dosegrouP (n=5), single bolus grouP (n=4) and conjunctve theraPygrOuP (n=5). Pulse pressures in alI the recanalized arteries6drOPPed tO less than 50% oftha in left.femral Brteq 5 hOUrspostthrOInolysis. Blood Pressures in righ femora arteryshowed no significant chang