Sustained reflow in dogs with coronary thrombosis with K2P, a novel mutant of tissue-plasminogen activator

Abstract

Coronary artery reocclusion after thrombolysis with human recombinant tissue-type plasminogen activator (rt-PA) is related to the short half-life of this agent in plasma. K2P, a mutant of rt-PA lacking the fibronectin fingerlike, epidermal growth factor-like and first kringle domains (amino acids 6 to 173) and having the glycosylation site Asn184 mutagenized to Gln, has been produced in Chinese hamster ovary cells. In this study we compared the thrombolytic effect of K2P and rt-PA in dogs with electrically induced coronary artery thrombosis. Both agents were given intravenously in equimolar amounts over 20 min after the occlusive thrombus was stable for 30 min; dogs were monitored for 1 h after reperfusion if flow occurred. Coronary blood flow was restored by rt-PA in 6 (60%) of 10 dogs. The restored flow lasted for 49 +/- 12 min and mean flow at 60 min from the start of reperfusion was 7 +/- 3 ml/min. The reocclusion rate was 50% (three of six dogs). Flow was restored in five (100%) of five dogs by K2P. The restored blood flow lasted during the entire 1-h observation period in all but one dog and mean flow at 60 min was 49 +/- 16 ml/min (p less than 0.02 vs. flow in rt-PA-treated dogs). Restored coronary blood flow showed marked cyclic flow variations in rt-PA-treated but not in K2P-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxic, thrombolytic, membrane stabilizing and anti-oxidant activities of <i>Hygrophila schulli</i>

“…The extracts are also worth chemical investigation to isolate specific anticancer agents. Thromboembolic disorders such as pulmonary emboli, deep vein thrombosis, strokes and heart attacks are the main causes of morbidity and mortality in developed countries (Nicolini et al, 1992). On the other hand, the first generation thrombolytic agents (streptokinase and urokinase) show relatively weak substrate specificity and can cause systemic fibrinolysis and associated bleeding complications (Marder, 1993).…”

THROMBOLYTIC AND MEMBRANE STABILIZING PROPERTIES OF METHANOLIC EXTRACTS OF AVICENNIA MARINA LEAVES & BARKS

“…Thrombosis is a fatal illness that is defined by the formation of blood clots (thrombus) within the vascular system owing to the imbalance of physiological condition system of physiological procedures that results in vascular blockade and whereas regaining it causes fatal consequences, like cerebral or infarction and even death 5 . Thromboembolic disorders like respiratory organ emboli, deep vein occlusion, strokes and heart attacks etc.…”

Antithrombotic potential of <i>Berberis calliobotrys</i> extract

“…Thrombosis is a grievous disorder that is typified by the evolution of a thrombus (blood clot) within the vascular system (Nicolini et al, 1992). Over 150 year ago, German pathologist Rudolf Virchow first postulated that a triad of conditions predispose to thrombus formation (Kyrle and Eichinger, 2009).…”