über die Verteilung von Diisopropyl-phosphorofluoridat (DFP) zwischen isoliertem Vorhofgewebe und zirkulierendem oxygenierten Vollblut von Meerschweinchen

Summary

The distribution of DFP has been investigated by several authors in intact animals and human beings. Since investigations of this kind depend on a rather large number of variables, in the present paper the distribution of³H-labelled DFP was studied in a simplified model using isolated guinea-pig atria incubated in oxygenated whole blood. The degree of cholinesterase-inhibition and the corresponding negative inotropic effect of acetylcholine has been simultaneously determined.

• 1. Taking the binding of DFP by the plasma proteins into account, the uptake of DFP by atrial tissue and erythrocytes was still rather low, since the tissue-medium ratio did not exceed 0.5. In addition to the uptake by erythrocytes there is an appreciable but easily reversible binding to the membrane.

• 2. The uptake processes approached equilibrium values after about 4 hours of incubation and revealed two exponential functions with different half life times.

• 3. The inhibition of the acetylcholinesterase of the red cells was proportional to the amount of DFP taken up. At the lowest DFP concentration (1.1×10⁻⁶M) the more sensitive butyrylcholinesterase of plasma and atrial tissue was already completely inhibited.

• 4. In the presence of DFP the acetylcholine-sensitivity of the electrically driven atria was increased as indicated by a parallel shift of the dose-response curves towards lower concentrations of ACh.