Cerebral Blood Flow Is Not Altered in Sheep with Pseudomonas aeruginosa Sepsis Treated with Norepinephrine or Nitric Oxide Synthase Inhibition

Abstract

The origin of cerebral dysfunction in patients with sepsis is still unclear. However, altered cerebral perfusion may play an important role in its pathogenesis. Using an established, chronic model of hyperdynamic ovine sepsis, we examined cerebral perfusion in 20 sheep subjected to a continuous infusion of live Pseudomonas aeruginosa. After 24 h of sepsis, the hypotensive sheep (reduction in mean arterial blood pressure by 16%; P < 0.05) received the nitric oxide synthase inhibitor N(G)-mono-methyl-L-arginine (L-NMMA; 7 mg. kg(-1). h(-1); n = 7), norepinephrine (NE; n = 7), or normal saline (control; n = 6). NE infusion was individually targeted to achieve the same increase in mean arterial blood pressure as that observed in matched sheep of the L-NMMA group. Regional perfusion was measured by using colored microspheres. Although L-NMMA caused a significant increase in systemic vascular resistance index (1167 +/- 104 versus 793 +/- 59 dyne. cm(-5). m(2); P < 0.05), it caused a change neither in cerebrovascular resistance nor in cerebral blood flow. When related to systemic blood flow, a redistribution of blood flow to the brain became obvious. The NE-associated increase in systemic blood pressure (98 +/- 5 versus 83 +/- 5; P < 0.05) was accompanied by an increase in cardiac output (7.8 +/- 0.5 versus 6.7 +/- 0.6; P < 0.05) and, hence, systemic perfusion. However, blood flow to the brain remained unaffected. Although detrimental vasoconstrictive effects of NE and L-NMMA, including cerebral hypoperfusion, are discussed, neither drug had any effect on cerebral perfusion during experimental hyperdynamic sepsis. Cerebral dysfunction is often found in septic patients. In this regard, it is debated whether vasopressor drugs, such as norepinephrine and L(G)-mono-methyl-L-arginine, have harmful effects on the cerebral circulation. During experimental hyperdynamic sepsis, however, neither drug altered cerebral vascular resistance or cerebral blood flow.