Halothane interactions with haemoglobin

Abstract

The perturbation of Hb by halothane was studied as a model system for the interaction of a general inhalational anesthetic agent with a protein. These interactions were studied with Fourier transform NMR techniques, and differences between the Hb proton spectra in the absence and presence of halothane were recorded over a range of pH values and anesthetic concentrations. These revealed a small number of conspicuous perturbations which persisted down to clinical concentrations of halothane, and over the whole pH range studied. These perturbations, which were also observed in Hb in whole red cells, strongly suggest either that the invasion of the protein surface and interior by the anesthetic is a very selective process, or that the protein only allows very specific distortions to occur. Assignments are offered for the histidine C2 resonances involved in the perturbation, and are based on comparisons between human and various animal [dog, horse, sheep, pig] oxyhemoglobins, and studies with human oxy- and deoxyhemoglobin. By using these assignments, an attempt was made to locate the area of strongest interaction between halothane and Hb through the perturbations which manifest themselves at the moelcular surface at or near the titratable histidine residues.