Effects of inhibition of endothelium-derived relaxation factor on hemodynamics and oxygen utilization during group B streptococcal sepsis in piglets

Objective To determine the effects of the inhibition of endothelium-derived relaxation factor in an animal model of neonatal group B streptococcal sepsis. Design Comparison of three experimental protocols: a) N-nitro-L-arginine; b) group B streptococcal; and c) group B streptococcal/N-nitro-L-arginine. Subjects Piglets, 1 to 2 wks old. Interventions Endothelium-derived relaxation factor inhibition was produced in nonseptic piglets by the infusion of a competitive inhibitor of nitric oxide synthase, N-nitro-L-arginine, at 30 mg/kg (N-nitro-L-arginine protocol; n = 6). Human group B streptococcal sepsis was modeled in piglets by the continuous infusion of live group B streptococcal organisms at approximately 5 x 10(9) organisms/kg cumulative dose (group B streptococcal protocol; n = 8). Endothelium-derived relaxation factor inhibition during a group B streptococcal sepsis was produced by N-nitro-L-arginine infusion during continuing group B streptococcal infusion (group B streptococcal/N-nitro-L-arginine protocol; n = 7). Measurements and main results Both N-nitro-L-arginine and group B streptococcal infusion significantly increased systemic and pulmonary vascular resistance and decreased cardiac output and oxygen delivery. N-nitro-L-arginine differed from group B streptococcal infusions in its effects on systemic blood pressure (BP) (N-nitro-L-arginine increased BP while group B streptococcal infusions did not), and pulmonary/systemic vascular resistance ratio (group B streptococcal infusions increased pulmonary/systemic vascular resistance ratio more than N-nitro-L-arginine did). The group B streptococcal/N-nitro-L-arginine group differed significantly from piglets receiving continued group B streptococcal infusion without N-nitro-L-arginine in cardiac output (significantly lower in group B streptococcal/N-nitro-L-arginine), oxygen delivery (significantly lower in group B streptococcal/N-nitro-L-arginine), and pulmonary vascular resistance (significantly higher in group B streptococcal/N-nitro-L-arginine). Conclusions Group B streptococcal sepsis in human newborns and in animal models of human newborns is characterized by a hemodynamic constellation of "cold shock"--increased vascular resistance and reduced systemic blood flow. Endothelium-derived relaxation factor inhibition during group B streptococcal sepsis in piglets exacerbated many of the adverse hemodynamic consequences of group B streptococcal infusion. We speculate that endothelium-derived relaxation factor inhibition has no foreseeable therapeutic role in neonatal septic shock.