Norepinephrine and N-omega-monomethyl-L-arginine in porcine septic shock -Effects on hepatic O-2 exchange and energy balance

We compared the effects of norepinephrine (NOR; n = 11) and the nonselectiv e nitric oxide synthase inhibitor N-omega-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow ((Q) over dot(liv)), O-2 exchange, and energy m etabolism over 24 h of hyperdynamic, normotensive porcine endotoxic shock. Endotoxin (ETX; n = 8) caused a continuous fall in mean arterial pressure ( MAP) despite a sustained 50% increase in cardiac output ((Q) over dot) achi eved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in (Q) over dot, while the comparable hemodynamic stabilization during L-NMMA infusion resulted from systemic vasoconstrictio n, increasing the systemic vascular resistance (SVR) about 30% from shock l evel after 6 h of treatment concomitant with a reduction in (Q) over dot to preshock values. Whereas NOR also increased (Q) over dot(liv) and, hence, hepatic O-2 delivery (hDo(2)), but did not affect hepatic O-2 uptake (hVo(2 )), L-NMMA influenced neither (Q) over dot(liv) nor hDo(2) and hVo(2). Mean capillary hemoglobin O-2 saturation (HbSc(O2)) on the liver surface as wel l as HbSc(O2) frequency distributions, which mirror microcirculatory O-2 av ailability, remained unchanged as well. Neither treatment influenced the ET X-induced derangements of cellular energy metabolism reflected by the progr essive decrease in hepatic lactate uptake rate and increased hepatic venous lactate/pyruvate ratios. ETX nearly doubled the endogenous glucose product ion (EGP) rate, which was further increased with NOR, whereas L-NMMA nearly restored EGP to preshock levels. Nevertheless, despite the different mecha nisms in maintaining blood pressure neither treatment influenced ETX-induce d liver dysfunction.