High-dose, brief-duration intravenous infusion of streptokinase in acute myocardial infarction: description of effects in the circulation.

The effects in the circulating blood of a 1-hour intravenous infusion of 1.5 X 10(6) units of streptokinase (SK) were measured during the subsequent 24-hour period in 7 patients with acute myocardial infarction. At the end of the infusion, the activator activity, expressed in SK units, averaged 65 U/ml, all of the plasminogen had disappeared, only a small amount of free plasmin was still present and functionally active alpha 2 antiplasmin had been reduced to 21% of the preinfusion level. All of the native fibrinogen had been degraded and the thrombin-coagulable protein was composed entirely of fragment X species, but the circulating plasma also contained significant amounts of the more extensively degraded fragments Y, D and E. The biologic half-life of the SK-induced activator activity was 23 minutes and that of the fibrinogen degradation products was 6.3 hours. The lytic effects persisted for 4 hours before any signs of recovery from the hemostatic defect were evident; considerable recovery was present at 25 hours.

A decade of experience with the Model 103 and 104 Beall valve prostheses.

Mitral or tricuspid valve replacement with the Beall Model 103 or 104 prosthesis has been associated with a high incidence of late prosthetic malfunction which has necessitated reoperation. Between 1972 and 1975, 57 patients underwent single valve replacement (55 mitral and two tricuspid) with Beall Model 103 or 104 valvular prostheses and survived at least 2 years. The mean follow-up time was 73.7 months (range 24 to 119 months). Of these patients, 22 required explantation of the prosthesis; there was an operative mortality of 27%. Major prosthetic malfunction occurred in four patients: Two occluders were embolized and two occluders were fixed in the open position. All four patients required urgent operation, and two of them died. The development of symptoms of congestive heart failure, systolic murmur, or hemolysis were the reasons for cardiac catheterizations and possible reoperation. Nineteen patients had cardiac catheterization. Fifteen of these subsequently underwent reoperation, with a mortality of 26%. Three patients were considered inoperable. Cardiac catheterization data revealed significant prosthetic regurgitation in all patients: pulmonary capillary pressure 29.9 mm Hg +/- 6.7 (standard deviation); V wave 31.5 mm Hg +/- 12.0; left ventricular end-diastolic pressure 18.0 mm Hg +/- 7.8. Comparison of hemolysis indicators in this group to those of asymptomatic patients revealed that the former had a significant elevation in lactic dehydrogenase (p = 0.038) and a lowered hematocrit value (p = 0.017). Waiting for severe symptomatic deterioration to justify reoperation risks the development of left ventricular dysfunction and possible emergency reoperation with a high operative mortality.

Human factor XIa cleaves fibrinogen: effects on structure and function.

Factor XIa, the enzymatic form of the factor XI zymogen, is generated as a result of factor XII-dependent surface activation in plasma. Factor XIa degrades high molecular weight kininogen, its cofactor for activation (which binds factor XIa to the surface), as well as cleaves and activates coagulation factor IX. In this report, we present evidence that factor XIa can also cleave fibrinogen and decrease the thrombin-catalyzed formation of the fibrin clot. Furthermore, the products of factor XIa-digested fibrinogen markedly inhibited the rate of polymerization of fibrin monomers. Factor XIa initially cleaved the A alpha-chain of fibrinogen and subsequently degraded the B beta-chain. However, the cleavage sites on both chains were distinct from those susceptible to thrombin. The gamma-chain was degraded only after prolonged incubation with factor XIa. Furthermore, the profile of fibrinogen proteolysis by factor XIa was distinctly different from that of plasmin-catalyzed fibrinogenolysis. Unlike plasmin, factor XIa was not able to cleave the NH2-terminus of the B beta-chain of fibrinogen. Moreover, factor XIa, unlike plasmin, failed to hydrolyze fibrin. Further study of the proteolytic digests of fibrinogen produced by factor XIa may give additional insight into the mechanism of polymerization of this protein.