Controlled Trial of Combined Urokinase and Dextran Sulfate Therapy in Patients With Acute Cerebral Infarction

Abstract

In this multiinstitute cooperative study, 143 patients were treated with either urokinase (UK) or combination of urokinase and dextran sulfate (UK-DS) within one to seven days following acute onset of cerebral thrombotic infarction. Of these, 81 randomized cases received a single dose of UK (2.83 X 10(5) units) by six-hour intravenous drip infusion and the remaining 62 received a combined dose of UK (2.84 X 10(5) units) and DS (3000 mg) for only one day. Moderate to marked clinical improvements assessed during the seven-day study period were observed in 30.9% of the patients treated with UK and in 61.3% of those with UK-DS, the latter being significantly higher. Hemorrhagic phenomena appeared in 3.2% of the cases treated with UK-DS and in none of those with UK alone, but mortality was 1.6% in the former and 2.5% in the latter. UK-DS produced a prompt and sustained increase in plasma fibrinolytic activity with transient and relatively minor disturbance of the blood coagulation system. The results indicate that combined therapy with UK and DS is more effective than UK alone for acute cerebral thrombotic infarction.

Progress in Intravenous Thrombolytic Therapy for Acute Stroke

“…It was not until the 1980s that the first clinical trials began to emerge in pursuit of the heretofore untreatable condition of acute ischemic stroke. In 1986, Fujishima et al 4 used urokinase vs urokinase plus dextran sulfate to treat 143 patients with acute stroke, reporting improvement in 74% of patients who received urokinase alone and 84% of patients who received the combination. However, there was no control arm to test the thrombolytic agent compared with the placebo and no blinding of assessments, standardization of outcomes, or standard protocol for imaging.…”

Low molecular weight dextran sulfate prevents complement activation and delays hyperacute rejection in pig‐to‐human xenotransplantation models

“…Whereas DXS has previously found application in various settings, including clinical studies [17,18], the new approach of this study lies in its application to xenotransplantation. The effect of DXS 5000 on HAR and complement activation was evaluated in pig‐to‐human xenotransplantation models.…”

“…In clinical studies of DXS species, for example as an anti‐viral therapeutic agent (DXS 7–8000 MW) for HIV [17] or for the treatment of acute cerebral thrombotic infarction in combination with urokinase [18], thrombocytopenia was described as a side‐effect after prolonged intravenous infusion. Binding of human platelets to pig endothelial cells, leading to thrombocytopenia, has been described earlier [24,25] and, in view of the clinical data, the use of DXS might aggravate this condition.…”

Addition of dextran sulfate to blood cardioplegia attenuates reperfusion injury in a porcine model of cardiopulmonary bypass☆

“…Furthermore, DXS in part improved the hemodynamic situation by ameliorating diastolic LV function and RV-and pulmonary artery pressures post-CPB. Whilst DXS has been used in a few patient trials [25], including CPB in children, [15] larger randomized clinical trials would be needed before judging the possible importance of the use of DXS in altering current clinical practice. However, in light of the fact that DXS at the current dose was not associated with any adverse events and was well tolerated, it remains to be substantiated whether a more aggressive treatment regimen, evaluated in a longer post-CBP follow-up and ultimately analyzed in human trials, may more markedly and sustainably improve post-CPB cardiac function and outcome.…”