HEMODYNAMIC EFFECTS OF MODIFIED HEMOGLOBIN IN OVINE SEPSIS ARE ANTAGONIZED BY L-ARGININE

Abstract

S125 Introduction: Modified hemoglobin solutions like pyridoxalated hemoglobin polyoxyethylene (PHP) reverse the hyperdynamic circulation in sepsis. [1] They bind nitric oxide (NO), a mediator for the hemodynamic changes in sepsis. [2,3] Their use is associated with pulmonary hypertension. We studied the effect of L-arginine, a NO precursor, after PHP administration in sepsis. Methods: Sheep were instrumented with arterial, venous, left atrial, and pulmonary catheters. After 5 days Ps. aeruginosa (6x106 CFU/kg/h) was infused for 32 h. After 24 hr of Ps., 20 mg/kg/h PHP was infused for the rest of the study in group PHP (n=14) and group Arg (n=6); group S (n=12) received the carrier solution. At 28h, group Arg received a bolus of 100mg/kg L-arginine followed by 500mg/kg/h for 1h. Statistical analysis by Anova. Results: Data in the graphs are presented as mean +/- SEM, closed squares: group Arg, triangles: group PHP; circles: group S. (Figure 1, Figure 2, and Figure 3)Figure 1Figure 2Figure 3Discussion: PHP increased systemic and pulmonary vascular resistance. L-arginine rapidly decreased the resistances to their 24hr levels after Ps. The administration of large amounts of L-arginine could cause a rise in NO production that exceeded the binding capacity of the low dose PHP infusion. L-arginine may be useful as a rapidly acting agent to reverse undesirable vasoconstriction after administration of hemoglobin in sepsis. This study was in part supported by Apex Bioscience. Inc.