Biomedical subjects
F Lund
Publications and source records attributed to F Lund.
Thrombolytic treatment with i.v. brinase of advanced arterial obliterative disease of the limbs.
The material includes 17 patients suffering from different degrees of chronic peripheral arterial disease (11 chronic patients stage III and IV, two patients with acute arterial occlusion, and four patients stage II). Presence and extent of arterial occlusion was ascertained by initial arteriography. In twelve of the patients amputation had been considered. The patients were treated by a series of i.v. infusions of brinase, a proteolytic enzyme from Aspergillus oryzae. The brinase inhibitor capacity in plasma was determined by the azocollagen technique. Dosage of brinase was calculated to retain a rest-inhibitor capacity in order to avoid free proteolytic activity. In five patients the enzyme was also given preoperatively by intra-arterial instillation prior to a series of i.v. brinase infusions. Thirteen patients showed clinical improvement after brinase treatment. The condition of two patients remained unchanged, and in two patients amputation could not be avoided. In fourteen patients the treatment results were followed by measurement of peripheral systolic blood pressure. In ten patients obvious increase of the peripheral systolic blood pressure was observed. Cutaneous microcirculation was studied in seven patients by i.v. sequential fluorescein angiography and signs of improved microcirculation (appearance time, intensity and/or extent of fluorescence) were found in all examined patients. One patient with acute arterial occlusion of the right leg with obstruction of blood flow from the external iliac artery showed complete disobliteration after a series of i.v. brinase infusions. Bleeding complications associated with brinase treatment were not observed in the material. In three patients brinase treatment was discontinued because of complications (2 brinase, 1 heparin).
Dosage of i.v. brinase in man based on brinase inhibitor capacity and coagulation studies.
In 17 patients a total of 148 brinase infusions were given. All patients but two had anticoagulant treatment (dicoumarol or heparin) during the brinase series. Dosage of brinase was based on determination of brinase inhibitor capacity in plasma (azocollagen technique) prior to infusion of the enzyme. Iv infusion of brinase lowered inhibitors in plasma. Good correlation was found between expected lowering and measured inhibitor values after brinase infusion. The stipulated safety margin for brinase inhibitor capacity could be maintained. alpha 1-antitrypsin showed irregular changes and alpha 2-macroglobulin values were decreased by iv infusions of brinase. Fibrinogen values were somewhat lowered after iv brinase infusion. Values for fibrinogen degradation products increased and the ethanol gelation test became positive. Thrombotest values were lowered and the activated partial thromboplastin time was prolonged in patients receiving dicoumarol and iv heparin respectively. Changes in other coagulation parameters were insignificant. In two patients transient renal failure was recorded, laboratory data indicated intravascular coagulation as a possible cause. None of these two patients were on anticoagulant treatment. One patient developed a haematoma of the forefoot during massive iv heparin treatment during a series of iv infusions of brinase. Bleeding complications due to brinase treatment were not observed.