Rapid infusion of plasma protein fraction(PPF) containing prekal1ikrein activator (PKA) may cause severe hypotension. It has been suggested, that such changes in blood pressure are due to PKA-mediated activation of the kallikrein system. We studied both in patients and in animals, whether a relationship exists between PKA activity in PPF, the plasma bradykinin (BK) level and changes in mean arterial pressure (MAP),during rapid infusion of PPF and albumin. Plasma Bk was measured by radioimmunoassay, using blood collected in a mixture of kallikrein and kininase-inhibitors. PKA was determined spectrophotometrically. PPF and albumin were infused (250 ml, 30 sec.) in the bypass circuit of patients undergoing open heart surgery. After infusion of PPF (29 U PKA/L), MAP decreased within 1.5 min. from 76±11 (SD) to 49 ± 9 mm Hg; concurrently the venous Bk concentration increased from 0.7 ± 0.1 to 1.7 ± 0.2 ng/ml (n=6). After albumin infusion (3 U PKA/L) MAP dropped from 71 ± 14 to 66 ± 13 mm Hg; the Bk concentration did not increase significantly (n=6). In rats, pretreated with the kininase II inhibitor BPP9A the effect of rapid infusion of different lots of PPF on arterial Bk concentration and MAP were compared. Both the decrease of MAP and the increase of arterial Bk concentration were proportional to the amount of PKA infused. Infusion of synthetic Bk provoked a similar fall in MAP at corresponding arterial Bk concentrations. After complete inhibition of PKAin PPF by CT-inhibitor, no effects on MAP or Bk level were observed. The ability of several lots of PPF to generate Bk (ng/ml/10 min.) in Hage- man factor deficient plasma closely correlated with the PKA content of PPF (n=25, r 0.95, p 0.005). From these observations we conclude that the hypotensive reactions after PPF infusion are mainly caused by the PKA mediated generation of Bk in the recipient.
Kallikrein specifically cleaves bradykinin (BK) from high molecular weight kininogen. Although measurement of BK in blood samples is potentially a sensitive index of intravascularkallilirein action, the rapid in activation of BK in the circulation(t =20 sec) limits the practical usefulness of BK assays. The present study was designed to develop a method which permits rapid measurement of circulating kallikrein in a large number of samples. Blood is collected in a mixture of kininase inhibitors and incubated for different periods of time before addition of soybean- and ovomucoid trypsin inhibiter. BK was measured by a radioimmunoassay. Cross-reacting kininogens were quantitatively separated from BK by precipitation with polyethyleneglycol. In 25 normal individuals this assay revealed a mean BK plasma level of 0.5 ng/ml±0.5(2SD) and the BK generation In vitro (ΔBK) of 1.5 ng/ml/20 min ± 1.0 (2SD). Upon activation of plasma with kaolin or dextransulphate, BK increased up to 800 ng/ml/20 min. In 3 out of 5 patients with asymptomatic hereditary Cl-INH deficiency, ΔBK was increased (range 7.0-11.1 ng/ml/20 min) whereas basal BK levels were normal. Increased ΔBK was found in 3 patients with pancreatitis and in 9 out of 26 patients with a malignancy (range 2.8+13.8 ng/ml/20 min)the basal BK plasma levels being normal. 2 of the latter patients showed signs of low grade DIC. It is thought that the BK-generation test detects circulating kallikrein.
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