Effects of Halogenated and Non-Halogenated Anesthetics on Diaspirin Cross-Linked Hemoglobin™-Induced Contractions of Porcine Pulmonary Veins

Abstract

Diaspirin crosslinked hemoglobin (DCLHb™) is a resuscitative fluid presently undergoing clinical trials. Administration of DCLHb is associated with an elevation of mean arterial pressure in vivo and contraction of isolated blood vessels in vitro. The mechanisms for the vascular actions are unknown but may be due to inhibition of nitric oxide (NO). Halothane has been reported to inhibit NO induced relaxation. We examined the effect of anesthetics on DCLHb induced contraction of blood vessels. Porcine pulmonary veins were excised, cut into rings and placed in organ chambers filled with 25 ml Krebs-Ringer solution (37°C). Following equilibration at their optimal length the rings were exposed to increasing concentrations of serotonin(10^-8M-10^-5M). Endothelial activity was confirmed by relaxation greater than 80% with ACh (10^-6M). DCLHb (1.5±10^-8M to 6±10^-7M) contracted porcine pulmonary veins (1.04±0.17g to 3.45±0.22g), and halothane (0.5% and 1%) significantly inhibited these DCLHb induced contractions in a dose-related manner (-41.6 ± 8.1% and -73.3 ± 8.2%, respectively). At equi-molar concentrations, isoflurane had no inhibitory activity. The relative effect of these volatile anesthetics is consistent with their inhibitory actions on other heme containing proteins. Propofol (10^-5M) only has inhibitory effects on lower concentrations of DCLHb. Fentanyl did not have inhibitory effects. These results suggest that halogenated anesthetics may interact with the heme iron of DCLHb and inhibit its binding with NO.