EFFECTS OF HALOGENATED AND NONHALOGENATED ANESTHETICS ON DIASPIRIN CROSS-LINKED HEMOGLOBIN(TM)-INDUCED CONTRACTIONS OF PORCINE PULMONARY VEINS

Diaspirin crosslinked hemoglobin (DCLHb(TM)) is a resuscitative fluid presently undergoing clinical trials. Administration of DCLHb is assoc iated with an elevation of mean arterial pressure in vivo and contract ion of isolated blood vessels in vitro. The mechanisms for the vascula r actions are unknown but may be due to inhibition of nitric oxide (NO ). Halothane has been reported to inhibit NO induced relaxation. We ex amined the effect of anesthetics on DCLHb induced contraction of blood vessels. Porcine pulmonary veins were excised, cut into rings and pla ced in organ chambers filled with 25 ml Krebs-Ringer solution (37 degr ees C). Following equilibration at their optimal length the rings were exposed to increasing concentrations of serotonin(10(-8)M-10(-5)M). E ndothelial activity was confirmed by relaxation greater than 80% with ACh (10(-6)M). DCLHb (1.5x10(-8)M to 6x10(-7)M) contracted porcine pul monary veins (1.04 +/- 0.17g to 3.45 +/- 0.22g), and halothane (0.5% a nd 1%) significantly inhibited these DCLHb induced contractions in a d ose-related manner (-41.6 +/- 8.1% and -73.3 +/- 8.2%, respectively). At equi-molar concentrations, isoflurane had no inhibitory activity. T he relative effect of these volatile anesthetics is consistent with th eir inhibitory actions on other heme containing proteins. Propofol(10( -5)M) only has inhibitory effects on lower concentrations of DCLHb. Fe ntanyl did not have inhibitory effects. These results suggest that hal ogenated anesthetics may interact with the heme iron of DCLHb and inhi bit its binding with NO.