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P-glycoprotein and multidrug resistance-associated protein transporters in the blood-brain barrier: another important brick in the wall
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BACKGROUND: Protamine, an immunologically active, cationic amine, has been suspected of impairing lung mechanics when administered after cardiopulmonary bypass (CPB) to reverse heparin. Whether such adverse changes are an effect of protamine itself, the formation of heparin-protamine complexes, the extent of heparin anticoagulation, or its chemical reversal is not known. METHODS AND RESULTS: Using a computer-controlled, forced-ventilation method over a variety of physiological tidal volume (V(T)) and frequency (f) combinations, we prospectively studied 18 adult, elective patients before systemic heparinization and after protamine reversal to confirm and, possibly, elucidate an etiology for any adverse pulmonary effects. Protamine and heparin doses, their sum (Sigma-dose) and differential (Delta-dose) doses, and activated clotting times were tabulated. In all patients, lung resistance (R(L)) and, to a lesser extent, elastance (E(L)) increased after CPB, compared with pre-CPB values (P <.05). However, R(L) particularly increased after CPB with increases correlated to the Delta-dose, where R(LPRE-->POST) = -0.037 [Delta-dose] - 0.56f \_ 0.019V(T) + 36.1 (r =.652, P <.05). No other significant correlations were found among the remaining clinical parameters and changes in either R(L) or E(L), or any chest wall component (all P >.05). CONCLUSIONS: The changes seen in R(L) after CPB were greatest in those patients receiving the most nearly balanced doses of heparin and protamine, and were not related significantly to the total heparin or protamine doses, or their sum. These suggests that the extent of anticoagulation reversal or formation of heparin-protamine complexes, and not protamine itself, are more responsible for changes seen in lung mechanics. The changes seen were limited solely to R(L), and not in either E(L) nor the chest wall mechanical properties.
