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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.

Bradykinin Mediated Hypotension After Infusion Of Prekalli - Krein Activator Containing Plasma Protein Fraction