Nitric Oxide Scavengers in Sepsis

Hyperdynamic sepsis can be induced in sheep by infusion of live bacteria. NO, a major mediator for the hemodynamic changes in sepsis, is scavenged by hemoglobin. Infusion of the modified hemoglobin PHP in septic sheep normalized mean arterial pressure to presepsis levels, increased systemic vascular resistance, reduced the dose of norepinephrine needed to increase blood pressure, and tended to improve myocardial contractility. PHP caused pulmonary hypertension. Hypoxic pulmonary vasoconstriction was not affected by PHP. Regional blood flow, although decreased in some vascular beds during sepsis, was not further compromised by PHP. PHP infusion increased renal glomerular filtration rate and urinary output. There was little effect on laboratory values of organ function. Pulmonary bacterial clearance was not different between the PHP treated animals compared with septic controls, but tissue bacterial colony counts were lower in the PHP group. The marked increase in endothelin-1 levels after PHP infusion suggests an interaction between both substances, but it is unclear whether some of the effects of PHP may in fact be related to action of endothelin-1. Future studies should be conducted to further clarify the influence of modified hemoglobin solutions on the host defense mechanisms and bacterial killing. In addition, more data are needed on the long-term effects of administration of modified hemoglobin and effects in patients with preexisting diseases other than sepsis.