Influence of an Ethylendiamine Derivative on Histamine Intoxication and Anaphylactic Shock in the Intact Guinea Pig and the Isolated Guinea Pig Heart

Abstract

Summary and Conclusions N-phenyl-N-ethyl-N'-diethylethylendiamine (1571F) injected intravenously in guinea pigs protected 11 of 15 animals against death following 1 to 6 MLD of histamine. 1571F injected intravenously in sensitized guinea pigs prevented fatal anaphylaxis in 17 of 21 animals receiving 1 to 4 MLD of specific antigen. 1571F in dilutions up to 0.1 mg per liter fluid reversed the usual decrease in the rate of coronary flow in the isolated perfused guinea pig heart following addition of histamine to the perfusate in 16 of 17 hearts. An actual increase in rate of coronary flow usually resulted (14 tests). Five to 10 mg of 1571F per liter of perfusion fluid prevented a decrease in rate of coronary flow in the isolated, perfused, sensitized guinea pig heart in 10 of 17 animals, following the addition of specific antigen to the perfusate. Decrease in rate of flow when it did occur was less than that expected in hearts perfused with normal Ringer-Locke solution in 5 of the 7 remaining animals. It may be concluded that 1571F is a highly efficient antagonist of the fatal outcome of histamine and anaphylactic shock in the guinea pig. All the manifestations of these shocks are not prevented by 1571F, however, since cyanosis and prostration occur even though death may not follow. Similarly, when added to the perfusion fluid of the isolated heart this drug exerts a striking effect in preventing the expected decrease in rate of coronary flow in histamine or anaphylactic shock, but fails to alter the increase in rate and amplitude of the heartbeat. It would seem that the drug acts in histamine and anaphylactic shock primarily to prevent contraction of smooth muscle, thus saving the life of the animal but not preventing the development of other manifestations of shock.